Publisher Health

Scientists have developed a new robot that can ‘mimic’ the two-handed movements of care-workers as they dress an individual.
Until now, assistive dressing robots, designed to help an elderly person or a person with a disability get dressed, have been created in the laboratory as a one-armed machine, but research has shown that this can be uncomfortable for the person in care or impractical.
To tackle this problem, Dr Jihong Zhu, a robotics researcher at the University of York’s Institute for Safe Autonomy, proposed a two-armed assistive dressing scheme, which has not been attempted in previous research, but inspired by caregivers who have demonstrated that specific actions are required to reduce discomfort and distress to the individual in their care.
It is thought that this technology could be significant in the social care system to allow care-workers to spend less time on practical tasks and more time on the health and mental well-being of individuals.
Dr Zhu gathered important information on how care-workers moved during a dressing exercise, through allowing a robot to observe and learn from human movements and then, through AI, generate a model that mimics how human helpers do their task.
This allowed the researchers to gather enough data to illustrate that two hands were needed for dressing and not one, as well as information on the angles that the arms make, and the need for a human to intervene and stop or alter certain movements.
Dr Zhu, from the University of York’s Institute for Safe Autonomy and the School of Physics, Engineering and Technology, said: “We know that practical tasks, such as getting dressed, can be done by a robot, freeing up a care-worker to concentrate more on providing companionship and observing the general well-being of the individual in their care. It has been tested in the laboratory, but for this to work outside of the lab we really needed to understand how care-workers did this task in real-time.

“We adopted a method called learning from demonstration, which means that you don’t need an expert to programme a robot, a human just needs to demonstrate the motion that is required of the robot and the robot learns that action. It was clear that for care workers two arms were needed to properly attend to the needs of individuals with different abilities.
“One hand holds the individual’s hand to guide them comfortably through the arm of a shirt, for example, whilst at the same time the other hand moves the garment up and around or over. With the current one-armed machine scheme a patient is required to do too much work in order for a robot to assist them, moving their arm up in the air or bending it in ways that they might not be able to do.”
The team were also able to build algorithms that made the robotic arm flexible enough in its movements for it to perform the pulling and lifting actions, but also be prevented from making an action by the gentle touch of a human hand, or guided out of an action by a human hand moving the hand left or right, up or down, without the robot resisting.
Dr Zhu said: “Human modelling can really help with efficient and safe human and robot interactions, but it is not only important to ensure it performs the task, but that it can be halted or changed mid-action should an individual desire it. Trust is a significant part of this process, and the next step in this research is testing the robot’s safety limitations and whether it will be accepted by those who need it most.”
The research, in collaboration with researchers from TU Delft and Honda Research Institute Europe, was funded by the Honda Research Institute Europe.

More than 80% of stroke survivors experience walking difficulty, significantly impacting their daily lives, independence, and overall quality of life. Now, new research from the University of Massachusetts Amherst pushes forward the bounds of stroke recovery with a unique robotic hip exoskeleton, designed as a training tool to improve walking function. This invites the possibility of new therapies that are more accessible and easier to translate from practice to daily life compared to current rehabilitation methods.
Following stroke, people often experience walking asymmetry, where one step is shorter than the other. The study, published in IEEE Transactions on Neural Systems and Rehabilitation Engineering, reveals that the robotic hip exoskeleton has the potential to effectively train individuals to modify their walking asymmetry, presenting a promising avenue for stroke rehabilitation.
The approach employed by the robotic exoskeleton is inspired by split-belt treadmills, which are specialized machines with two side-by-side belts moving at different speeds. Prior research has shown that repeated training on a split-belt treadmill can reduce walking asymmetry in stroke patients.
Wouter Hoogkamer, assistant professor of kinesiology and author on the paper, has spent the last decade studying split-belt treadmills. “Split-belt treadmill training is designed to exaggerate a stroke patient’s walking asymmetry by running the belts under each foot at different speeds. Over time, the nervous system adapts, such that when the belts are set to the same speed, they walk more symmetrically.”
Unfortunately, there are limits to the benefits gained from treadmill-based training methods. “What is learned on a treadmill does not completely transfer to overground contexts,” says Banu Abdikadirova, mechanical and industrial engineering doctoral candidate and lead study author. “This is because walking on a treadmill is not exactly the same as walking overground.”
“The ultimate goal of gait rehabilitation is not to improve walking on a treadmill — it is to improve locomotor function overground,” says Meghan Huber, assistant professor of mechanical and industrial engineering and senior author on the paper. “With this in mind, our focus is to develop methods of gait rehabilitation that translate to functional improvements in real-world contexts.”
With this motivation, the UMass team sought a novel way to exaggerate walking asymmetry without a treadmill.

This proof-of-concept study showed that applying resistive forces about one hip joint and assistive forces about the other with their exoskeleton mimicked the effects of split-belt treadmill training in neurologically intact individuals.
Now that the research team has proven that the exoskeleton can alter gait asymmetry, they are eager to move their research into overground contexts that are more akin to the real world.
“Because our exoskeleton is portable, it can be used during overground walking,” says Mark Price, a postdoctoral researcher in mechanical and industrial engineering and kinesiology and author on the paper. “We can build upon the successes of split-belt treadmill training with this device to enhance the accessibility of gait training and enhance the transfer of training benefits into everyday walking contexts.”
The researchers also plan to expand their work by measuring the neural changes caused by walking with the exoskeleton and testing this new method on stroke survivors.
“A portable exoskeleton offers numerous clinical benefits,” says Abdikadirova. “Such a device can be seamlessly integrated into the daily lives of chronic stroke survivors, offering an accessible way to increase training time, which is critical for improving walking. It can also be used during early intervention in hospitals for improved functional outcomes.”
The robotic hip exoskeleton is just one of the innovative devices designed to study and enhance gait function developed by the collaborative team of undergraduate students, graduate students, and postdoctoral researchers from the Human Robot Systems Lab, led by Huber, and the Integrative Locomotion Lab, led by Hoogkamer.
“It is inspiring to witness the innovations that emerge when individuals from diverse backgrounds unite under a shared mission,” says Huber. “Only through this type of cross-disciplinary research can we engineer technologies that can have a meaningful impact on people’s lives.”

Research conducted by Dr Shota Nakanoh in a collaboration between Dr Teresa Rayon’s lab at the Institute and Professor Ludovic Vallier’s lab at the Wellcome-MRC Cambridge Stem Cell Institute has determined that the degree of cell crowding in the early human embryo influences whether cells develop as extra-embryonic cells or become a part of the embryo and eventually give rise to skin, hair and nails. The research is published in the current issue of Science Advances.
Combining the new culture method with three-dimensional culture and single cell RNA sequencing analysis, Dr Nakanoh, the lead researcher on the project, used human pluripotent stem cells (hPSC) to learn more about how amniotic and surface ectoderms arise in human embryos at around gastrulation (around two weeks after fertilisation).
The mystery of similar but different tissues — amniotic and surface ectoderms
Amniotic ectoderm is a single cell layer that forms the membrane surrounding the developing embryo. It also provides essential signals for human embryo development, however how the amniotic membrane comes about is still not fully known in humans.
Surface ectoderm is a dense sheet of epidermal progenitors, which gives rise to the surface covering of the body, such as skin, and the associated features of teeth, hair and fingernails. Its artificial production is of medical interest if technologies to generate it could be improved.
Amniotic and surface ectoderm cells are specialised at an early stage of development and largely share biological features, such as gene expression patterns and signal requirements. It has been a mystery why these distinct tissues are so similar and how they differentiate during development.
Cell crowding affects cell identity
Dr Nakanoh customised culture conditions for hPSCs and found that the supplements Activin A, BMP4, a GSK3-beta inhibitor, and a MEK inhibitor promoted their differentiation into amniotic ectoderm. Using a co-culture technique to form cellular aggregates, he was able to confirm the ability of the generated amniotic ectoderm cells to initiate gastrulation. Also, single cell RNA sequencing analysis suggested the differentiation pathway for amniotic ectoderm, where surface ectoderm genes are expressed before the activation of the amniotic ectoderm gene programme.

Comparison of the gene expression data against public data from primate embryos at comparable developmental stages, performed with the expertise of Dr Irina Mohorianu, Head of Bioinformatics at the CSCI, validated the cell types generated in the culture system, demonstrating their similarity to the corresponding embryonic tissues. Moreover, the developmental pathway through surface ectoderm state to amniotic ectoderm state was also observed in primate embryos.
Vitally, Dr Nakanoh identified that the distinction between the two cell types depends on cell density; where cells become amniotic ectoderm in sparse conditions. In contrast, high density culturing led to cells that expressed markers for surface ectoderm but not amniotic ectoderm. These cells were also able to differentiate into a downstream epidermal cell type, keratinocytes, which represent a key cell type in the skin. The researchers tested variations in the culture media but cell density was the only factor that influenced the cell fate choice between amniotic ectoderm and surface ectoderm.
The research team also found that the new culture system produces cells like extraembryonic mesoderm, which is not yet well characterised in human embryos.
Dr Shota Nakanoh, a postdoctoral researcher in the Rayon lab, said: “Amnion protects the embryo and provides key developmental cues while surface ectoderm contributes to a substantial part of adult body. Both cell types are of high clinical interest and are important elements for successful in vitro models for human embryos. Although there are protocols to differentiate cells to either amniotic or surface ectoderms, researchers were not able to make a clear distinction between these cell types. Our findings about cellular density as a key regulator fills this knowledge gap and thus facilitate us to be more certain about generating the cell types of interest.”
Applying this cell crowding effect back to the developing human embryo, the researchers propose how these similar tissues are differentiated in the pre-gastrulation embryo, where amniotic ectoderm arises as a loose sheet with relatively small numbers of cells, while surface ectoderm is formed as a continuous dense sheet of cells.
Enabling better stem cell embryo models
A method to correctly specify amnion formation is important to be able to recapitulate human embryo development as closely as possible using stem cell-based embryo models. These models are increasingly being used to explore human development beyond the technical and regulatory limits that govern human embryo research.

Dr Teresa Rayon, tenure-track group leader in the Institute’s Epigenetics research programme, said: “We have only recently begun to explore the generation of amnion during human development. These findings advance our understanding on how to generate extra-embryonic cells in the lab in vitro, and sheds light on the mechanisms that drive the formation of cell types at the stages that correspond to the ‘black box’ of human development. Given the growing interest in using stem cell embryo models as proxies of human embryos, this work provides more knowledge for the generation of successful integrated models.”
Prof. Vallier, now Professor of Stem Cells in Regenerative Therapies at the Berlin Institute of Health at Charité (BIH), said: “Our culture system also generates extra-embryonic mesoderm, another tissue not studied well in human embryos. It will provide better understanding of human development and could improve our knowledge about diseases affecting first step of foetal life. This work also opens the door for new studies regarding the role of cellular density in cell fate decision.”

A new study finds younger adults look and feel older on stressful days — but only on days when they also feel they have relatively less control over their own lives.
“There’s substantial research that tells us stress makes older adults feel their age, or even feel older than they actually are,” says Shevaun Neupert, corresponding author of the study and a professor of psychology at North Carolina State University. “And the literature tells us that when seniors feel older than they actually are, that is associated with a host of negative health outcomes. However, there is little research examining this issue in younger adults — people in their teens, 20s and 30s. Having a deeper understanding of this phenomenon across all age groups could help us develop interventions that protect our mental and physical well-being.
“This work may be particularly timely, as stress researchers are seeing an increase in the amount of stress younger adults are experiencing now, when compared to the amount of stress previous generations experienced when they were young.”
For this study, researchers collected data from 107 younger adults between the ages of 18 and 36 (mean age was around 20). Study participants completed a baseline survey followed by a detailed daily survey for eight consecutive days. The daily surveys were designed to capture the amount of stress they were experiencing each day, how much control they felt they had over their lives that day, and how old they felt and looked on that day.
“The key finding was that on days when study participants reported experiencing higher levels of stress than they normally did, they also reported looking and feeling older,” Neupert says. “However, this was only true on days when study participants also reported feeling that they had less control over their lives than they normally did.
“It’s also worth noting that both the levels of stress and the levels of control were relative.”
In other words, a person could report having relatively low levels of stress — but if the level of stress was higher than they normally reported, researchers saw the effect. By the same token, people could report feeling they still had significant levels of control over their lives — but if it was less control than they normally reported, researchers saw the effect.
“For one thing, this tells us that the phenomenon of stress making people feel older is not limited to older adults — it happens to young people too,” Neupert says.
“It’s also important because we know that experiencing chronic stress over time can have adverse effects, and that people generally report increasing levels of stress as they move from young adulthood to midlife — their 40s and 50s,” Neupert says. “If these young people are already experiencing historically high levels of stress for their age, and that stress is affecting how old they feel, it will be important for us to pay close attention to the markers we use to assess stress-related physical and mental health for this generation.”

Oral cancers and precancerous mouth lesions are considered especially difficult to diagnose early and accurately.
For one, biopsies are expensive, invasive, stressful for the patient and can lead to complications. They’re also not feasible if repeated screenings of the same lesion are required.
But a team of researchers, led by a clinician scientist at the Case Western Reserve University School of Dental Medicine, has discovered a noninvasive, low-cost test to detect oral cancer, monitor precancerous lesions and determine when a biopsy is warranted.
Their findings, published online March 4 in the journal Cell Reports Medicine, are based on a scoring system linked to the levels of two proteins in cells brushed from suspicious oral lesions of patients at dental clinics or the ear, nose and throat department at University Hospitals (UH).
One of the proteins (human beta defensin 3 or hBD-3) is expressed at high levels in early-stage oral cancer, while the second (hBD-2) is low or unchanged.
The ratio of hBD-3 to hBD-2 in the lesion site — over the ratio of the two proteins on the opposite, normal site — generates a score, called the beta defensin index (BDI).
A score above a predetermined threshold implies cancer; anything below does not. Determining the levels of the proteins and quantifying the BDI is done routinely in a lab.

The BDI was independently validated using identical protocols at CWRU/UH, University of Cincinnati Medical Center and West Virginia University School of Dentistry.
“When we first discovered hBD-3, we saw it acted as a ‘good guy,’ involved in wound-healing and killing microbes,” said Aaron Weinberg, chair of the Department of Biological Sciences at the Case Western Reserve School of Dental Medicine and the study’s lead researcher. “When we found it was regulated the same way certain cells grow uncontrollably, we started studying hBD-3 in the context of oral cancer.
“Imagine our surprise when this Dr. Jekyll turned out to be Mr. Hyde,” he said. “We found it was not only promoting tumor growth but was overexpressed in the early stages of the disease, while another member, hBD-2, wasn’t changing. This difference in levels of expression of the two proteins compared to the opposite side in the same patient led us to examine the BDI’s ability to distinguish cancer from benign lesions.”
Weinberg credits School of Dental Medicine instructor Santosh Ghosh for navigating the BDI scoring process.
Head and neck cancer (HNC), of which oral cancer is about 90%, is the seventh-most prevalent malignancy in the world, and developing countries are witnessing a rise in its incidence. HNC makes up about 5% of all cancers worldwide and 3% of all malignancies in the United States, according to the National Institutes of Health. There are about 640,000 cases of HNC per year, resulting in about 350,000 deaths worldwide, mainly in socioeconomically disadvantaged populations and underserved communities.
The study’s lab-based approach, which is now patented, can reduce biopsies in primary care clinics by 95% because it can tell clinicians who actually needs a biopsy, said Weinberg, also secondarily appointed in the Departments of Pathology and Otolaryngology at the Case Western Reserve School of Medicine. The test can also be used in developing countries where oral cancer is rampant and pathology services are questionable or lacking, he said.
The positive data from the lab-based approach has inspired the development of a point-of-care (POC) device in collaboration with Umut Gurkan, the Wilbert J. Austin Professor of Engineering at the Case School of Engineering. The POC diagnostic approach measures the protein ratio and could be used directly in a clinic, providing results within half-hour.
Working through Case Western Reserve’s Technology Transfer Office, a patent for the device is pending, setting up possible manufacturing and clinical validation as a next step.
Discovery, clinical validation studies and POC technology development were supported by the National Institute of Dental and Craniofacial Research, National Cancer Institute, Case Coulter Translational Research Partnership and Ohio Third Frontier Technology Validation and Start-Up Fund.

A new cellphone app developed by physician-scientists at UPMC and the University of Pittsburgh, which uses artificial intelligence (AI) to accurately diagnose ear infections, or acute otitis media (AOM), could help decrease unnecessary antibiotic use in young children, according to new research published today in JAMA Pediatrics.
AOM is one of the most common childhood infections for which antibiotics are prescribed but can be difficult to discern from other ear conditions without intensive training. The new AI tool, which makes a diagnosis by assessing a short video of the ear drum captured by an otoscope connected to a cellphone camera, offers a simple and effective solution that could be more accurate than trained clinicians.
“Acute otitis media is often incorrectly diagnosed,” said senior author Alejandro Hoberman, M.D., professor of pediatrics and director of the Division of General Academic Pediatrics at Pitt’s School of Medicine and president of UPMC Children’s Community Pediatrics. “Underdiagnosis results in inadequate care and overdiagnosis results in unnecessary antibiotic treatment, which can compromise the effectiveness of currently available antibiotics. Our tool helps get the correct diagnosis and guide the right treatment.”
According to Hoberman, about 70% of children have an ear infection before their first birthday. Although this condition is common, accurate diagnosis of AOM requires a trained eye to detect subtle visual findings gained from a brief view of the ear drum on a wriggly baby. AOM is often confused with otitis media with effusion, or fluid behind the ear, a condition that generally does not involve bacteria and does not benefit from antimicrobial treatment.
To develop a practical tool to improve accuracy in the diagnosis of AOM, Hoberman and his team started by building and annotating a training library of 1,151 videos of the tympanic membrane from 635 children who visited outpatient UPMC pediatric offices between 2018 and 2023. Two trained experts with extensive experience in AOM research reviewed the videos and made a diagnosis of AOM or not AOM.
“The ear drum, or tympanic membrane, is a thin, flat piece of tissue that stretches across the ear canal,” said Hoberman. “In AOM, the ear drum bulges like a bagel, leaving a central area of depression that resembles a bagel hole. In contrast, in children with otitis media with effusion, no bulging of the tympanic membrane is present.”
The researchers used 921 videos from the training library to teach two different AI models to detect AOM by looking at features of the tympanic membrane, including shape, position, color and translucency. Then they used the remaining 230 videos to test how the models performed.

Both models were highly accurate, producing sensitivity and specificity values of greater than 93%, meaning that they had low rates of false negatives and false positives. According to Hoberman, previous studies of clinicians have reported diagnostic accuracy of AOM ranging from 30% to 84%, depending on type of health care provider, level of training and age of the children being examined.
“These findings suggest that our tool is more accurate than many clinicians,” said Hoberman. “It could be a gamechanger in primary health care settings to support clinicians in stringently diagnosing AOM and guiding treatment decisions.”
“Another benefit of our tool is that the videos we capture can be stored in a patient’s medical record and shared with other providers,” said Hoberman. “We can also show parents and trainees — medical students and residents — what we see and explain why we are or are not making a diagnosis of ear infection. It is important as a teaching tool and for reassuring parents that their child is receiving appropriate treatment.”
Hoberman hopes that their technology could soon be implemented widely across health care provider offices to enhance accurate diagnosis of AOM and support treatment decisions.
Other authors on the study were Nader Shaikh, M.D., Shannon Conway, Timothy Shope, M.D., Mary Ann Haralam, C.R.N.P., Catherine Campese, C.R.N.P., and Matthew Lee, all of UPMC and the University of Pittsburgh; Jelena Kova?evi?, Ph.D., of New York University; Filipe Condessa, Ph.D., of Bosch Center for Artificial Intelligence; and Tomas Larsson, M.Sc, and Zafer Cavdar, both of Dcipher Analytics.
This research was supported by the Department of Pediatrics at the University of Pittsburgh School of Medicine.

An inexpensive, cavity-fighting liquid called silver diamine fluoride (SDF) works as well as dental sealants to keep tooth decay at bay in a school cavity prevention and treatment program, according to a new study by researchers at NYU College of Dentistry.
The study, which followed more than 4,000 elementary school students for four years and is published in JAMA Pediatrics, shows that SDF is an effective alternative to sealants, and can increase access to dental care while reducing costs.
Dental cavities are the most prevalent chronic disease in children and can lead to pain, school absences, and lower academic performance. To prevent cavities, especially among children less likely to see a dentist, the Centers for Disease Control and Prevention (CDC) supports the use of school sealant programs. In sealant programs, dental professionals visit schools to apply a thin, protective coating to the surface of teeth that hardens and safeguards against decay.
SDF has emerged as another promising treatment for fighting cavities. Originally approved by the FDA for treating tooth sensitivity, the solution is brushed onto the surface of teeth, killing decay-causing bacteria and remineralizing teeth to prevent further decay.
“A growing body of research shows that SDF — which is quicker to apply and less expensive than sealants — can prevent and arrest cavities, reducing the need for drilling and filling,” said Richard Niederman, DMD, professor of epidemiology & health promotion at NYU College of Dentistry and the study’s senior author.
SDF in schools
Researchers at NYU College of Dentistry led CariedAway, the nation’s largest school-based cavity prevention study, to compare the use of SDF and traditional sealants. The study included approximately 4,100 children in New York City elementary schools; more than a quarter of kids had untreated cavities at the start of the study.

At each school visit, a team of health professionals examined children’s teeth and applied either sealants or SDF followed by fluoride varnish, depending on which treatment the school was randomly assigned to receive. Sealants were administered by dental hygienists, while SDF was applied by either dental hygienists or registered nurses, all under the supervision of a dentist. Starting in 2018, the team visited each school twice a year, although the COVID-19 pandemic and school closures led to missed visits.
The researchers reported last year in the journal JAMA Network Open that a single treatment of either SDF or sealants prevented 80% of cavities and kept 50% of existing cavities from worsening two years later. The team continued their study for another two years, and in their study published in JAMA Pediatrics, found that SDF and sealants prevented roughly the same number of cavities after children were followed for a total of four years. Moreover, both sealants and SDF reduced the risk of decay at each follow-up visit.
“Our longitudinal study reaffirms that both sealants and SDF are effective against cavities. SDF is a promising alternative that can support school-based cavity prevention — not to replace the dental sealant model, but as another option that also prevents and arrests decay,” said Ryan Richard Ruff, PhD, MPH, associate professor of epidemiology & health promotion at NYU College of Dentistry and the study’s first author.
“Most research shows that SDF can stop a cavity from progressing further. Our study demonstrated that SDF can prevent cavities from happening in the first place,” said Tamarinda Barry Godín, DDS, MPH, associate program director and supervising dentist for CariedAway, research scientist at NYU College of Dentistry, and the study’s coauthor.
An “untapped” oral health workforce
Embracing SDF for cavity prevention and treatment in schools could keep kids from needing fillings, saving families and the healthcare system money. Yet these programs can only succeed if there are enough health professionals to provide care.
The NYU researchers found that children who had SDF applied by dental hygienists and registered nurses had similar outcomes, suggesting that nurses — including school nurses — could play a crucial role in cavity prevention programs.
“Nurses may be an untapped resource for addressing oral health inequities,” added Ruff. “Our results suggest that nurses can effectively provide this preventive care, which could dramatically improve access, given the role of school nurses and the size of the nursing workforce.”
This research was funded by the Patient-Centered Outcomes Research Institute (PCS-160936724). The CariedAway cavity prevention model is currently being used in three New Hampshire school districts, supported by Northeast Delta Dental.

A vaccine against Zika virus is safe and effective when administered both before and during pregnancy, according to new research published in npj Vaccines.
The purified, inactivated Zika vaccine (ZPIV) candidate, developed by Walter Reed Army Institute of Research (WRAIR), is being evaluated in animal models at Texas Biomedical Research Institute (Texas Biomed) in collaboration with WRAIR and Trudeau Institute in New York.
The vaccine candidate has previously been shown to effectively block prenatal Zika virus transmission when given to nonhuman primates prior to pregnancy. This new study goes a critical step further, studying what happens when the vaccine is administered during pregnancy.
“This is a giant step forward,” says Jean Patterson, Ph.D., Professor Emeritus at Texas Biomed. “We have very strong evidence that this vaccine could protect fetal health during the next Zika outbreak.”
Zika virus is primarily transmitted by mosquitoes. It does not typically cause serious illness in most people; the biggest threat is to pregnant women and developing fetuses. During the 2015-2016 Zika outbreak in the Americas, there was a surge in miscarriages and babies born with extremely small heads and other severe birth defects, collectively called Congenital Zika Syndrome. Zika virus continues to circulate at low levels and has been detected in 89 countries and territories to date.
“Zika virus continues to infect people around the world and present a significant risk to maternal-fetal health,” says Stephen J. Thomas, M.D., an inventor of the ZPIV vaccine and a study collaborator. “Because of this, advancing the development of vaccine candidates and studying different use scenarios is incredibly important.”
The vaccine candidate has completed Phase 1 clinical trials in humans and was well tolerated and elicited an immune response. But clinical trials usually exclude pregnant people, leaving key questions unanswered about whether vaccination during pregnancy would be safe and potent. This new study is believed to be the first to evaluate a Zika vaccine during pregnancy in nonhuman primates. Marmosets, a small nonhuman primate that typically has twins and triplets, are sensitive to Zika virus infection and closely mirror what happens in pregnant humans.

Given the drastic changes that the immune system undergoes during pregnancy, the researchers were not sure if the vaccine, when given during early pregnancy, would generate a protective immune response, such as creating protective antibodies.
“The antibody response when given during pregnancy was similar to the level we observed when administered before pregnancy,” says In-Jeong Kim, Ph.D., a principal investigator at Trudeau Institute. “That is very exciting.”
The vaccine candidate prevented placental damage and sufficiently blocked transmission of Zika virus from mother to fetus. The viral load in placentas and fetuses was significantly lower in the vaccinated group versus the unvaccinated group. Growth and development of fetuses of vaccinated adult marmosets exposed to Zika virus were similar to controls not exposed to the virus. No adverse effects were detected.
What remains to be studied is if protection will last throughout pregnancy and whether offspring born from vaccinated females challenged with the virus during pregnancy are free of Congenital Zika Syndrome.
“We hope to garner more interest and funding to pursue those next steps,” says Dr. Patterson.

Childhood lead exposure, primarily from paint and water, is a significant health concern in the United States, but a new study has identified a surprising additional source of lead exposure that may disproportionately harm children: firearms.
A team led by researchers at Brown University found an association between household firearm ownership and elevated lead levels in children’s blood in 44 states, even when controlling for other major lead exposure sources.
Lead exposure from firearms is far less explored than from recognized sources like water or lead-based paint, but may be equally dangerous for children’s health, said Christian Hoover, a Ph.D. candidate in epidemiology at Brown’s School of Public Health, who is the lead author of the study published in the Journal of Pediatrics.
“This is very concerning because we don’t have a system of monitoring lead from firearm use, as we do with residential paint, and there is no system in place to minimize or prevent children’s exposure to lead in firearms,” Hoover said. “Firearm use is a relatively unchecked source of childhood exposure to lead. There’s currently no way to stop the exposure from happening and no interventions when it does.”
In the study, the association between elevated lead levels and firearm use was almost as strong as the association for lead-based paint, Hoover noted.
Lead levels in children in the United States have been persistently high for decades. While public health measures have been put in place to prevent and reduce childhood lead poisoning from paint and drinking water, blood lead levels haven’t concordantly dropped in significant measures, Hoover said.
Firearm-related take-home lead occurs when an individual discharges a firearm that uses lead-based ammunition and primer, which are the most commonly used in the United States, Hoover said. The lead dust settles on clothes and personal items, such as phones or bags, as well as in vehicles and common spaces. Children are more vulnerable to lead than adults due to their tendency to ingest contaminants through normal hand-to-mouth behaviors.

“Typically the places where the firearm-related lead collects, such as in carpets, are places where young children spend a considerable amount of time,” said Hoover, who is a co-investigator at the Harvard Injury Control Research Center.
A previous study led by Hoover found a link between firearms and elevated lead levels in children’s blood in cities and towns in Massachusetts; this new study involved the 44 U.S. states that report public health data on child blood lead levels.
Since there is no governmental database covering firearm ownership across states, the researchers used a widely-accepted proxy measure developed by the RAND Corporation to estimate state levels of household gun ownership. This metric combines data on firearm suicides, hunting licenses, subscriptions to Guns and Ammo magazine and background checks. They compared the data from the proxy measure with reports from the Centers for Disease Control and Prevention of blood lead concentration surveillance data for children under 6. The analysis spanned the years between 2012 and 2018.
According to the study, for every 10% increase in the number of households that report owning a gun, there is an approximate 30% increase in cases of elevated pediatric blood lead levels.
Childhood exposure to lead increases the risk of behavioral problems, reduced cognitive abilities and poor growth and development. There is no safe level of lead exposure, said Joseph Braun, a professor of epidemiology and director of the Center for Children’s Environmental Health at Brown.
“Despite public health efforts to prevent or reduce childhood lead exposure, a substantial proportion of U.S. children are still exposed,” Braun said. “Thus, we need to identify other modifiable sources of lead exposure in children’s environments to protect their developing bodies and brains.”
The authors concluded that the data suggest firearms are a notable source of child lead exposure that requires more targeted research.
Alan Fossa, a postdoctoral research associate in environmental health at Brown, also contributed to this study.
This research was supported by the National Institute of Environmental Health Sciences (R21 ES034187).

In a discovery that opens the door to a less invasive way of treating some serious disorders before birth, UC San Francisco scientists have found that delivering medicine through amniotic fluid is as effective as delivering it to the fetal brain via cerebrospinal fluid. The experiment was done in mice with a genetic disorder called Angelman syndrome.
Treating genetic diseases like Angelman in utero could prevent serious symptoms that begin while the fetus is still developing. It’s also easier to access neurons in the fetal brain because the blood-brain barrier that normally acts as a filter to prevent molecules from reaching the brain is not yet fully formed.
The treatment uses therapeutic molecules called antisense oligonucleotides, or ASOs, that can alter the expression of genes through interactions with RNA, which creates proteins.
“ASOs are currently given to children with diseases affecting the nervous system,” said Tippi MacKenzie, MD, a fetal and pediatric surgeon at UCSF Benioff Children’s Hospitals and the senior author of the study, which appears in Molecular Therapy. “However, children who have a severe version of a genetic condition may have irreversible damage by the time they are born that cannot be addressed after birth.”
Previous research has shown that Angelman syndrome, a severe neurological condition marked by intellectual disabilities, seizures and abnormal gait, can be diagnosed before birth, and that expression of the part of the gene that causes the syndrome can be manipulated prenatally.
The treatment improved the motor function and learning of the mice pups after they were born. And injecting the therapy directly into the amniotic fluid allowed it to circulate into the intestines, lungs, liver, kidneys and stomach, and helped reinstate gene expression in critical parts of the brain.
“By injecting into the amniotic fluid, we could give a much higher dose than when we injected into the cerebrospinal fluid,” MacKenzie said. “Injecting this way also created a more ‘slow release’ approach.”
The researchers hope this will enable them to treat conditions such as pulmonary hypertension and cystic fibrosis prenatally.
“Both types of prenatal injections we tried, into the cerebrospinal fluid and into the amniotic fluid, allowed the therapy to penetrate deep regions of the brain that are critical areas to treat for Angelman Syndrome,” said Maria Clark, B.S., a UCSF research associate in MacKenzie’s lab. “This is a big hurdle to overcome when treating genetic conditions of the nervous system.”
The team is now working with a large animal model to determine whether ASOs delivered into the amniotic fluid can cross into the brain and spinal cord as well as they did in mice. They are also speaking to parents whose children are affected by Angelman syndrome and related disorders to understand their perspectives on seeking prenatal therapy.