Monday, February 27, 2023

New study to help bereaved caregivers

25% of former dementia caregivers experience clinically problematic levels of grief.

Grant and Award Announcement

ARIZONA STATE UNIVERSITY

A new grant from the National Institute on Aging, a division of the National Institutes of Health, will fund research at Arizona State University to collect the largest quantitative sample of bereaved dementia caregivers to date, in order to provide tools and resources to improve their lives.

Assistant Professor Zachary Baker with ASU's Center for Innovation in Healthy and Resilient Aging is the principal investigator of the study. He says former caregivers are a growing, diverse group that often feels ‘ultra-invisible’ as a majority of currently available support is focused on those actively providing care.

“The reality is they lost their mom or their husband, or somebody really important to them and as many as 25% of these former caregivers are getting clinical symptoms and what I mean by that is not just normal grief or sadness but something that is stopping their life,” said Baker.

Even those whose symptoms don’t rise to the clinical level still suffer from higher rates of depression and loneliness. And their numbers are increasing. According to Baker, within 10 years, most people living with Alzheimer’s disease and related dementias will die, creating 9+ million new bereaved caregivers.

“So aside from a lot of sadness and subclinical depression and less quality of life, we’re talking about millions of people who can’t function but nobody is talking about them or thinking about their needs,” he said.

With $726,711 in funding, this three-year study is looking to change that.

The research aims to understand first, who is going to do better or worse after the person in their care has passed away, and then try to figure out the things that people who are coping well are already doing that work for them and share those solutions with others who are struggling.

“I would love for that ultra-invisibility term to be completely irrelevant,” said Baker.

They are actively recruiting former dementia caregivers to join the study and working on an initiative to try to expand the study to Spanish speakers in order to reach more communities.

If you are interested in participating or know someone who might be interested please call 602-543-4492 (x34492) or email, formerdementiacare@asu.edu, to learn more.


UCF researcher studies bird wings to improve stability in aerial vehicles

Aerospace engineering researcher Samik Bhattacharya received a $441,000 grant to study bird wing morphing, which could improve the stability of unmanned aerial vehicles in strong gusts of wind.

Grant and Award Announcement

UNIVERSITY OF CENTRAL FLORIDA

Samik Bhattacharya 

IMAGE: UNIVERSITY OF CENTRAL FLORIDA ASSISTANT PROFESSOR OF AEROSPACE ENGINEERING SAMIK BHATTACHARYA IS STUDYING THE MORPHING POWER OF BIRD WINGS IN TURBULENCE THROUGH A THREE-YEAR, $441,000 GRANT FROM THE U.S. AIR FORCE OFFICE OF SCIENTIFIC RESEARCH. THE GOAL IS TO UNCOVER THE SECRETS OF BIRD STABILITY AND ENGINEER A COMPARABLE SOLUTION FOR UAVS AND MAVS. view more 

CREDIT: UNIVERSITY OF CENTRAL FLORIDA

ORLANDO, Feb. 22, 2023 – Many airplane passengers grit their teeth, white-knuckle their armrests and say a silent prayer for their flight to go smoothly. They know that any sudden disturbance in airflow can cause turbulence — and in turn, a severe case of anxiety.

But in smaller aircraft, such as unmanned aerial vehicles or micro air vehicles, turbulence is more than a bumpy ride. It can severely affect the stability of these vehicles and cause them to lose control. On the other hand, nature’s natural fliers — birds — know how to retain control during airflow disturbances.

Assistant Professor of Aerospace Engineering Samik Bhattacharya is studying the morphing power of bird wings in turbulence through a three-year, $441,000 grant from the U.S. Air Force Office of Scientific Research. The goal is to uncover the secrets of bird stability and engineer a comparable solution for UAVs and MAVs.

“Birds have perfected the art of unsteady flow control through millions of years of evolution,” Bhattacharya says. “They don’t use any separate flaps or slats; rather, they morph their wings and use their feathers to achieve similar feats. However, we don’t know how to utilize similar morphing capabilities in man-made flight vehicles.”

To study these morphing capabilities, Bhattacharya and his team of researchers in the Experimental Fluid Mechanics Lab have 3D printed a set of wings made of black agilus plastic. This material is very flexible, so the 3D model can be morphed along the wingspan to mimic the collapsible structure of real bird wings.

The team will test the wings’ morphing capabilities in high turbulence through a state-of-the-art gust generator system that will be funded by the AFOSR grant. This system will be integrated with the towing tank that’s already operating in the EFML lab. The wings will be placed in the tank with a sensor that can measure the lift and drag forces. Images of the flow field will also be captured with the aid of high-speed cameras.

Along with the gust generator, the AFOSR grant will also fund the hiring of graduate students to work on this project. Bhattacharya says he’s grateful for the award, which is highly competitive.

“It feels great to receive this award from AFOSR, especially because the program that funded this work is one of the few federal programs that support this type of fundamental fluid mechanics research,” he says. “It’s very challenging to receive funding from this program.”

Bhattacharya joined UCF’s College of Engineering and Computer Science as an assistant professor in 2016. He received his doctoral degree in aerospace engineering from The Ohio State University, his master’s degree in aerospace engineering from Auburn University and his bachelor’s degree in mechanical engineering from the National Institute of Technology in Warangal, India. He is also a researcher with UCF’s Center for Advanced Turbine and Energy Research.

Writer: Marisa Ramiccio, UCF College of Engineering and Computer Science

Keeping babies alive will lower population growth – new research

New research showing high infant mortality rates are contributing to an incessant rise of the global human population supports arguments for greater access to contraception and family planning in low- and middle-income nations.

Peer-Reviewed Publication

FLINDERS UNIVERSITY

Child in Marrakech 

IMAGE: KEEPING CHILDREN ALIVE WILL HELP CURB POPULATION GROWTH view more 

CREDIT: (C) COREY BRADSHAW, FLINDERS UNIVERSITY

Keeping babies alive will lower population growth – new research 

 

New research showing high infant mortality rates are contributing to an incessant rise of the global human population supports arguments for greater access to contraception and family planning in low- and middle-income nations.

 

In an article published in PLOS ONE, research led by Professor Corey Bradshaw, Matthew Flinders Professor of Global Ecology from Flinders University and Peter Le Souëf, Professor of Paediatrics from The University of Western Australia has found that with higher baby death rates and larger household sizes (as an indicator of population density), fertility rates are higher. 

 

In the first study of its kind, Professor Bradshaw, says it provides a compelling argument that the United Nations Sustainable Development Goals for reducing infant mortality can be accelerated by increasing access to family planning.

 

“Although it sounds counterintuitive, higher baby death rates are linked to higher population growth because the more babies a women loses, the more children she is likely to have. Family planning, including access to quality contraception, enables women to plan pregnancies better and therefore reduce infant mortality to curb the so-called ‘replacement’, or ‘insurance’ effect,” Professor Bradshaw says. 

 

“We evaluated six conditions thought to influence a woman’s fertility — availability of family planning, quality of family planning, education, religion, mortality, and socio-economic conditions, across 64 low- to middle-income countries.”

 

The research specifically tested whether

  • increasing the availability of family planning is associated with reduced fertility;
  • increasing the quality of family-planning services is associated with reduced fertility;
  • increasing years of female education is associated with reducing fertility;
  • increased fertility is observed in countries with a higher prevalence of adherents of Catholicism or Islam, two main religions that expressly dictate elements of fertility and/or family structure;
  • a larger mean household size is positively correlated with fertility, and lower socio-economic conditions; and
  • higher mortality (both infant and maternal) is associated with higher fertility.

 

Co-author Dr Melinda Judge from The University of Western Australia’s Medical School says, “Keeping babies alive actually reduced average fertility and helps put the brakes on population growth. Essentially, higher infant mortality and a larger household size increased fertility, whereas greater access to any form of contraception decreased fertility.”

 

“Interestingly, female education, home visits by health workers, quality of family planning services, and religious adherence all had weak, if any, contribution at the scale of entire countries.” 

 

Professor Bradshaw says the United Nations Sustainable Development Goals 3 (good health and wellbeing) and 5 (gender equality) emphasise the basic right to exercise control over sexual and reproductive health through universal access to family planning. 

 

The world is not on track to meet Goal 3 to reduce global maternal mortality to less than 70 per 100,000 live births and end preventable deaths of newborns and children under 5 years of age by 2030. 

 

“Our results show the best pathway toward reaching these targets is by providing readily available and high-quality family-planning services. These actions will not only to decrease fertility rates, they will also to lower the number of unintended pregnancies, infant deaths, and maternal deaths.

 

“These findings support the notion that to encourage continued declines in global fertility, both infant survival rates plus access to contraception need to be increased”, explains Professor Bradshaw.

 

Co-author Chitra Saraswati also of The University of Western Australia’s Medical School says, “Recommendations for measures to decrease infant mortality emphasise improving the quality of antenatal care, increasing the number of trained healthcare staff at births, and improving postnatal care for both infants and mothers. Given the evidence that large households can worsen child health, improving living conditions to ameliorate high-density living could also indirectly result in lower fertility.” 

 

“Allowing parents to choose family planning by providing readily available, modern methods of contraception can be expected to improve infant survival as well as reduce maternal mortality. This is because parents can plan and space their births, and being able to decide to have fewer children also has the potential to facilitate better investment in the overall health and well-being of families. It emphasises the importance of providing access to contraception as a direct contribution to decreasing infant mortality.”

 

“If we don’t act now to achieve the UN’s Sustainable Development Goals, fertility will rise, more children will die, and more women will succumb to birth-related deaths,” Professor Bradshaw concludes. 

 

Lower infant mortality, lower household size, and more access to contraception reduce fertility in low- and middle-income nations. Bradshaw, CJA, C Perry, MA Judge, CM Saraswati, J Heyworth, PN Le Souëf. 2023. PLOS ONEhttp://doi.org/10.1371/journal.pone.0280260

First transient electronic bandage speeds healing by 30%

Bandage also monitors the healing process, alerting clinicians to issues in real time

Peer-Reviewed Publication

NORTHWESTERN UNIVERSITY

Electronic bandage 

IMAGE: PROFESSOR GUILLERMO AMEER HOLDS THE SMALL, THIN, FLEXIBLE DEVICE IN HIS HAND. view more 

CREDIT: NORTHWESTERN UNIVERSITY

  • Wireless, battery-free bandage delivers electrical signals to help wounds heal
  • Bandage monitors healing, streaming data in real time to a smartphone or tablet
  • After healing is complete, bandage and electronics harmlessly absorb into the body

EVANSTON, Ill. — Northwestern University researchers have developed a first-of-its-kind small, flexible, stretchable bandage that accelerates healing by delivering electrotherapy directly to the wound site.

In an animal study, the new bandage healed diabetic ulcers 30% faster than in mice without the bandage.

The bandage also actively monitors the healing process and then harmlessly dissolves — electrodes and all — into the body after it is no longer needed. The new device could provide a powerful tool for patients with diabetes, whose ulcers can lead to various complications, including amputated limbs or even death.

The research will be published online in the Feb. 22 issue of the journal Science Advances. It marks the first bioresorbable bandage capable of delivering electrotherapy and the first example of a smart regenerative system.

“When a person develops a wound, the goal is always to close that wound as quickly as possible,” said Northwestern’s Guillermo A. Ameer, who co-led the study. “Otherwise, an open wound is susceptible to infection. And, for people with diabetes, infections are even harder to treat and more dangerous. For these patients, there is a major unmet need for cost-effective solutions that really work for them. Our new bandage is cost-effective, easy to apply, adaptable, comfortable and efficient at closing wounds to prevent infections and further complications.”

“Although it’s an electronic device, the active components that interface with the wound bed are entirely resorbable,” said Northwestern’s John A. Rogers, who co-led the study. “As such, the materials disappear naturally after the healing process is complete, thereby avoiding any damage to the tissue that could otherwise be caused by physical extraction.”

An expert in regenerative engineering, Ameer is the Daniel Hale Williams Professor of Biomedical Engineering at Northwestern’s McCormick School of Engineering and professor of surgery at Northwestern University Feinberg School of Medicine. He also directs the Center for Advanced Regenerative Engineering (CARE) and the predoctoral Regenerative Engineering Training Program, funded by the National Institutes of Health. Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery at McCormick and Feinberg. He also directs the Querrey Simpson Institute for Bioelectronics.

Power of electricity

Nearly 30 million people in the U.S. have diabetes, and about 15 to 25% of that population develops a diabetic foot ulcer at some point in their lives. Because diabetes can cause nerve damage that leads to numbness, people with diabetes might experience a simple blister or small scratch that goes unnoticed and untreated. As high glucose levels also thicken capillary walls, blood circulation slows, making it more difficult for these wounds to heal. It’s a perfect storm for a small injury to evolve into a dangerous wound.

The researchers were curious to see if electrical stimulation therapy could help close these stubborn wounds. According to Ameer, injuries can disrupt the body’s normal electrical signals. By applying electrical stimulation, it restores the body’s normal signals, attracting new cells to migrate to the wound bed.

“Our body relies on electrical signals to function,” Ameer said. “We tried to restore or promote a more normal electrical environment across the wound. We observed that cells rapidly migrated into the wound and regenerated skin tissue in the area. The new skin tissue included new blood vessels, and inflammation was subdued.”

Historically, clinicians have used electrotherapy for healing. But most of that equipment includes wired, bulky apparatuses that can only be used under supervision in a hospital setting. To design a more comfortable product that could be worn around the clock at home, Ameer partnered with Rogers, a bioelectronics pioneer who first introduced the concept of bioresorbable electronic medicine in 2018.

Remote control

The two researchers and their teams ultimately developed a small, flexible bandage that softly wraps around the injury site. One side of the smart regenerative system contains two electrodes: A tiny flower-shaped electrode that sits right on top of the wound bed and a ring-shaped electrode that sits on healthy tissue to surround the entire wound. The other side of the device contains an energy-harvesting coil to power the system and a near-field communication (NFC) system to wirelessly transport data in real time.

The team also included sensors that can assess how well the wound is healing. By measuring the resistance of the electrical current across the wound, physicians can monitor progress. A gradual decrease of current measurement relates directly to the healing process. So, if the current remains high, then physicians know something is wrong.

By building in these capabilities, the device can be operated remotely without wires. From afar, a physician can decide when to apply the electrical stimulation and can monitor the wound’s healing progress.

“As a wound tries to heal, it produces a moist environment,” Ameer said. “Then, as it heals, it should dry up. Moisture alters the current, so we are able to detect that by tracking electrical resistance in the wound. Then, we can collect that information and transmit it wirelessly. With wound care management, we ideally want the wound to close within a month. If it takes longer, that delay can raise concerns.”

In a small animal model study, the researchers applied electrical stimulation for just 30 minutes a day. Even this short amount of time accelerated the closure by 30%.

Disappearing act

When the wound is healed, the flower-shaped electrode simply dissolves into the body, bypassing the need to retrieve it. The team made the electrodes from a metal called molybdenum, which is widely used in electronic and semiconductor applications. They discovered that when molybdenum is thin enough, it can biodegrade. Furthermore, it does not interfere with the healing process.

“We are the first to show that molybdenum can be used as a biodegradable electrode for wound healing,” Ameer said. “After about six months, most of it was gone. And we found there’s very little accumulation in the organs. Nothing out of the ordinary. But the amount of metal we use to make these electrodes is so minimal, we don’t expect it to cause any major issues.”

Next, the team plans to test their bandage for diabetic ulcers in a larger animal model. Then, they aim to test it on humans. Because the bandage leverages the body’s own healing power without releasing drugs or biologics, it faces fewer regulatory hurdles. This means patients potentially could see it on the market much sooner.

The study, “Bioresorbable, wireless battery-free system for electrotherapy and impedance sensing at wound sites,” was partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases and CARE. Northwestern biomedical engineering doctoral candidate Joseph Song is co-first author.

A close-up look at the bandage's two electrodes: : A tiny flower-shaped electrode that sits right on top of the wound bed and a ring-shaped electrode that sits on healthy tissue to surround the entire wound.

Professor Guillermo Ameer holds the small, thin, flexible device.

CREDIT

Northwestern University

Climate change, urbanization drive major declines in L.A.’s birds

A new study uses current and historical bird surveys to reveal how land use change has amplified — and in some cases mitigated — the impacts of climate change on birds in Los Angeles and the Central Valley

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - BERKELEY

Sutter Buttes retake 

IMAGE: PHOTO RETAKES FOR SUTTER BUTTES (SUTTER COUNTY) SHOWING THE CHANGE IN LAND USE. THE UPPER IMAGE SHOWS A 1931 PHOTO OF SUTTER BUTTES IN THE MIDDLE OF THE CENTRAL VALLEY WEST OF MARYSVILLE, WHICH WAS SURVEYED FOR BIRDS BY JOSEPH GRINNELL AND COLLEAGUES AT THE TIME. PHOTO TAKEN BY JEAN M. LINSDALE AND PROVIDED WITH PERMISSION OF THE MUSEUM OF VERTEBRATE ZOOLOGY, UNIVERSITY OF CALIFORNIA, BERKELEY. THE LOWER IMAGE SHOWS A PHOTO OF SUTTER BUTTES IN 2016 WHEN BIRD RESURVEYS WERE CONDUCTED. YOUNG WALNUT TREES COMPOSE THE FOREGROUND, ILLUSTRATING THE EXPANSION OF AGRICULTURE INTO THE FORMER GRASSLAND AREA. PHOTO TAKEN BY SARAH A. MACLEAN AND PROVIDED WITH PERMISSION OF THE MUSEUM OF VERTEBRATE ZOOLOGY, UNIVERSITY OF CALIFORNIA, BERKELEY. view more 

CREDIT: UNIVERSITY OF CALIFORNIA, BERKELEY

Berkeley — Climate change isn’t the only threat facing California’s birds. Over the course of the 20th century, urban sprawl and agricultural development have dramatically changed the landscape of the state, forcing many native species to adapt to new and unfamiliar habitats.

In a new study, biologists at the University of California, Berkeley, use current and historical bird surveys to reveal how land use change has amplified — and in some cases mitigated — the impacts of climate change on bird populations in Los Angeles and the Central Valley.

The study found that urbanization and much hotter and drier conditions in L.A. have driven declines in more than one-third of bird species in the region over the past century. Meanwhile, agricultural development and a warmer and slightly wetter climate in the Central Valley have had more mixed impacts on biodiversity.

“It's pretty common in studies of the impact of climate change on biodiversity to only model the effects of climate and not consider the effects of land use change,” said study senior author Steven Beissinger, a professor of environmental science, policy and management at UC Berkeley and a researcher at the campus’s Museum of Vertebrate Zoology (MVZ). “But we’re finding that the individual responses of different bird species to these threats are likely to promote unpredictable changes that complicate forecasts of extinction risk.”

The study, publishing this week in the journal Science Advances, presents the latest results from UC Berkeley’s Grinnell Resurvey Project, an effort to revisit and document birds and small mammals at sites first surveyed a century ago by UC Berkeley professor Joseph Grinnell.

In the current study, the researchers resurveyed birds at 71 sites in L. A. and the Central Valley. They then used their findings — along with current and historical data on land use, average temperature and rainfall — to analyze how shifts in the climate and landscape may have contributed to changes in bird populations.

In L.A., they found that 40% of bird species were present at fewer sites today than they were 100 years ago, while only 10% were present at more sites. Meanwhile, in the Central Valley, the proportion of species that experienced a decline (23%) only slightly outnumbered the proportion that increased (16%). In many cases, opposing responses to climate and land use change by bird species, where one threat caused a species to increase while another caused the same species to decline, moderated the impacts of each threat alone.

The decline in bird species in L.A. over the past century is similar to the shocking bird community collapse that the research team documented in national parks in the Mojave Desert over the past 100 years, and linked to heat stress from climate change.

“The Central Valley had less change, in general — there were winners and losers,” Beissinger said. “Whereas in L.A., we saw mostly losers.”

Windfalls and double whammies

Grinnell was a teenager when he first started documenting birds in the late 1890s near his childhood home of Pasadena, California. He later perfected his detailed approach to surveying as a professor of zoology at UC Berkeley and the first director of the MVZ.

“In those days, they didn't have fancy binoculars. They didn't have recordings of bird calls. So, they had to get in and learn the birds through the resources that were available. Oftentimes that was from specimens in museums. Sometimes that was through popular guides or handbooks,” Beissinger said. “Grinnell was ahead of his time in the way that he was taking field notes, and he was really draconian in also making all his students take those notes.”

Grinnell’s meticulous field notes have allowed Beissinger and his team to construct a historical baseline of California’s bird life at the turn of the 20th century. The notes are so detailed that the researchers are able to reconstruct the birds encountered each day and account for the ways new technologies, such as better binoculars and field guides, have made it easier for contemporary biologists to detect birds. This analysis has allowed the team to make direct comparisons between the current and historical bird surveys.

To tease apart the disparate and sometimes opposing impacts of land use change and climate change, the researchers analyzed historical maps of urban development and agriculture to determine how the landscape at each study site had been modified during the 20th century. They also obtained historical average temperatures and rainfall at each site.

In L.A., they found that species such as Anna’s hummingbird and the American crow were able to adapt to both hotter and drier conditions and to urban development, experiencing what the researchers call a population “windfall.” Other species, such as the western meadowlark and the lark sparrow, were negatively impacted by both changes, instead experiencing a “double whammy.”

Species that experienced mixed impacts include the black phoebe, the great egret, the house wren and the blue-gray gnatcatcher.

“Our findings really highlight the fact that we’ve got climate and land use change happening at the same time, creating happy conditions for some species, while other species are declining from the same changes,” Beissinger said. “Sometimes, species might also be pushed and pulled in different directions from the climate and land use changes.”

Bird species in the Central Valley also experienced a combination of windfalls, double whammies and mixed impacts, but the proportion of species that experienced windfalls was much higher in the Central Valley than in L.A. and nearly offset the proportion that experienced double whammies.

“There are some species that have been able to persist under the agricultural changes, and some that even colonized and increased because of those changes. But they tend to be species that are more common and widespread, and the more sensitive species are the ones that started disappearing when the natural grasslands were replaced by agriculture,” Beissinger said. “In the urban areas, there are just fewer species that are able to find what they need and avoid the city hazards.”

Additional co-authors of the paper include Sarah A. MacLean of the University of La Verne and Kelly J. Iknayan and Perry de Valpine of UC Berkeley. This work was supported by grants from the National Science Foundation (DEB 1457742, DEB 1911334 and DEB 1601523), the National Geographic Society (9972-16), a UC Berkeley Chancellor’s Fellowship and a Research Professorship from the Miller Institute.

Birds recorded in by Joseph Grinnell his notebook on April 13, 1895 at Santa Anita near Arcadia, California.

A hand drawn sketch by Tracy Storer of the 1912 site surveyed for birds near Rumsey in the Central Valley.

CREDIT

Steven Beissinger, University of California, Berkeley

Custom, 3D-printed heart replicas look and pump just like the real thing


The soft robotic models are patient-specific and could help clinicians zero in on the best implant for an individual.

Peer-Reviewed Publication

MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Heart Simulator 

IMAGE: CUSTOM, 3D-PRINTED HEART REPLICAS ARE PATIENT-SPECIFIC AND COULD HELP CLINICIANS ZERO IN ON THE BEST IMPLANT FOR AN INDIVIDUAL. view more 

CREDIT: MELANIE GONICK, MIT

No two hearts beat alike. The size and shape of the the heart can vary from one person to the next. These differences can be particularly pronounced for people living with heart disease, as their hearts and major vessels work harder to overcome any compromised function.

MIT engineers are hoping to help doctors tailor treatments to patients’ specific heart form and function, with a custom robotic heart. The team has developed a procedure to 3D print a soft and flexible replica of a patient’s heart. They can then control the replica’s action to mimic that patient’s blood-pumping ability.

The procedure involves first converting medical images of a patient’s heart into a three-dimensional computer model, which the researchers can then 3D print using a polymer-based ink. The result is a soft, flexible shell in the exact shape of the patient’s own heart. The team can also use this approach to print a patient’s aorta — the major artery that carries blood out of the heart to the rest of the body.

To mimic the heart’s pumping action, the team has fabricated sleeves similar to blood pressure cuffs that wrap around a printed heart and aorta. The underside of each sleeve resembles precisely patterned bubble wrap. When the sleeve is connected to a pneumatic system, researchers can tune the outflowing air to rhythmically inflate the sleeve’s bubbles and contract the heart, mimicking its pumping action. 

The researchers can also inflate a separate sleeve surrounding a printed aorta to constrict the vessel. This constriction, they say, can be tuned to mimic aortic stenosis — a condition in which the aortic valve narrows, causing the heart to work harder to force blood through the body.

Doctors commonly treat aortic stenosis by surgically implanting a synthetic valve designed to widen the aorta’s natural valve. In the future, the team says that doctors could potentially use their new procedure to first print a patient’s heart and aorta, then implant a variety of valves into the printed model to see which design results in the best function and fit for that particular patient. The heart replicas could also be used by research labs and the medical device industry as realistic platforms for testing therapies for various types of heart disease.

“All hearts are different,” says Luca Rosalia, a graduate student in the MIT-Harvard Program in Health Sciences and Technology. “There are massive variations, especially when patients are sick. The advantage of our system is that we can recreate not just the form of a patient’s heart, but also its function in both physiology and disease.”

Rosalia and his colleagues report their results in a study appearing today in Science Robotics. MIT co-authors include Caglar Ozturk, Debkalpa Goswami, Jean Bonnemain, Sophie Wang, and Ellen Roche, along with Benjamin Bonner of Massachusetts General Hospital, James Weaver of Harvard University, and Christopher Nguyen, Rishi Puri, and Samir Kapadia at the Cleveland Clinic in Ohio.

Print and pump

In January 2020, team members, led by mechanical engineering professor Ellen Roche, developed a “biorobotic hybrid heart” — a general replica of a heart, made from synthetic muscle containing small, inflatable cylinders, which they could control to mimic the contractions of a real beating heart.

Shortly after those efforts, the Covid-19 pandemic forced Roche’s lab, along with most others on campus, to temporarily close. Undeterred, Rosalia continued tweaking the heart-pumping design at home.

“I recreated the whole system in my dorm room that March,” Rosalia recalls.

Months later, the lab reopened, and the team continued where it left off, working to improve the control of the heart-pumping sleeve, which they tested in animal and computational models. They then expanded their approach to develop sleeves and heart replicas that are specific to individual patients. For this, they turned to 3D printing.

“There is a lot of interest in the medical field in using 3D printing technology to accurately recreate patient anatomy for use in preprocedural planning and training,” notes Wang, who is a vascular surgery resident at Beth Israel Deaconess Medical Center in Boston.

An inclusive design

In the new study, the team took advantage of 3D printing to produce custom replicas of actual patients’ hearts. They used a polymer-based ink that, once printed and cured, can squeeze and stretch, similarly to a real beating heart.

As their source material, the researchers used medical scans of 15 patients diagnosed with aortic stenosis. The team converted each patient’s images into a three-dimensional computer model of the patient’s left ventricle (the main pumping chamber of the heart) and aorta. They fed this model into a 3D printer to generate a soft, anatomically accurate shell of both the ventricle and vessel.

The team also fabricated sleeves to wrap around the printed forms. They tailored each sleeve’s pockets such that, when wrapped around their respective forms and connected to a small air pumping system, the sleeves could be tuned separately to realistically contract and constrict the printed models.

The researchers showed that for each model heart, they could accurately recreate the same heart-pumping pressures and flows that were previously measured in each respective patient.

“Being able to match the patients’ flows and pressures was very encouraging,” Roche says. “We’re not only printing the heart’s anatomy, but also replicating its mechanics and physiology. That’s the part that we get excited about.”

Going a step further, the team aimed to replicate some of the interventions that a handful of the patients underwent, to see whether the printed heart and vessel responded in the same way. Some patients had received valve implants designed to widen the aorta. Roche and her colleagues implanted similar valves in the printed aortas modeled after each patient. When they activated the printed heart to pump, they observed that the implanted valve produced similarly improved flows as in actual patients following their surgical implants.

Finally, the team used an actuated printed heart to compare implants of different sizes, to see which would result in the best fit and flow — something they envision clinicians could potentially do for their patients in the future.

“Patients would get their imaging done, which they do anyway, and we would use that to make this system, ideally within the day,” says co-author Nyugen. “Once it’s up and running, clinicians could test different valve types and sizes and see which works best, then use that to implant.”

Ultimately, Roche says the patient-specific replicas could help develop and identify ideal treatments for individuals with unique and challenging cardiac geometries.

“Designing inclusively for a large range of anatomies, and testing interventions across this range, may increase the addressable target population for minimally invasive procedures,” Roche says.

This research was supported, in part, by the National Science Foundation, the National Institutes of Health, and the National Heart Lung Blood Institute.

###

Written by Jennifer Chu, MIT News Office

Doxycycline does not prevent STIs among cisgender women


Reports and Proceedings

HENNEPIN HEALTHCARE RESEARCH INSTITUTE

February 20, 2023 – Researchers from the University of Washington (UW), Kenya Medical Research Institute (KEMRI), and Hennepin Healthcare Research Institute (HHRI) announced results at CROI from a clinical trial demonstrating that doxycycline taken after sex does not prevent bacterial sexually transmitted infections (STIs) – chlamydia or gonorrhea – among cisgender women. The dPEP Kenya Trial was conducted in Kisumu, Kenya, to evaluate the effectiveness of doxycycline postexposure prophylaxis (PEP) to prevent bacterial STIs. The results of the study have been highly anticipated, as this is the first study of doxycycline PEP among cisgender women, following multiple studies that showed a high level of STI protection with doxycycline use among cisgender men and transgender women in France and the United States.

Differences in anatomy, antibiotic resistance, and adherence offer possible explanations for the lack of efficacy among cisgender women when it worked for cisgender men and transgender women, and the research team is working to understand the potential role of these differences. “Doxycycline PEP didn’t work for cisgender women in Kenya, but the need for STI prevention is increasing around the world,” said Dr. Jenell Stewart, the dPEP Kenya Study Director, Infectious Disease Physician at Hennepin Healthcare and University of Minnesota.

Biological differences between the vagina/cervix and rectum may explain why doxycycline didn’t prevent STIs in cisgender women; however, the approach to treatment of STIs doesn’t differ by sex. Antibiotic resistance offers an explanation for why gonorrhea wasn’t prevented, but it doesn’t explain why chlamydia wasn’t prevented. There are no known cases of antibiotic resistant chlamydia; however, the rate of doxycycline resistant gonorrhea was very high, including 100% of the infections acquired prior to starting the study. Self-reported adherence was high but imperfect and frequency and timing of doxycycline use among cisgender women in the trial is being evaluated further. All participants were also taking daily HIV PrEP pills (a medicine to prevent HIV), and none of the participants got HIV during the year they were in the study.

At a single site in Kisumu, Kenya, the study enrolled 449 cisgender women who were taking daily oral HIV pre-exposure prophylaxis (PrEP) and were randomized to receive doxycycline or standard of care. 18% of participants had an STI at the time they entered the study and over the course of the study the rate of STIs remained high – an annual incidence of 27%, which is comparable to rates among men who have sex with men in high income countries. There were 109 new STIs diagnosed, 50 among those using doxycycline PEP compared to 59 among those randomized to no doxycycline and standard of care, during the course of the 12-month follow-up. Most, 78%, of the new STIs diagnosed were chlamydia, 35 among people taking doxycycline PEP and 50 among standard of care, which was not statistically different. Only one new case of syphilis was diagnosed in this study, consistent with other studies in the region, and therefore, the impact of doxycycline PEP on preventing syphilis among cisgender women could not be evaluated.

“The results from the study are deeply disappointing, and we are committed to understanding why doxycycline PEP did not work in this population and also determining the next steps for how to identify prevention tools that will work for and can be used by women,” said Prof. Elizabeth Bukusi, a Principal Investigator of the dPEP Kenya Trial and Senior Principal Clinical Research Scientist at the Kenya Medical Research Institute.

Bacterial STIs in women can lead to lasting and severe consequences including pelvic inflammatory disease, chronic pain, infertility, pregnancy complications, and increased susceptibility to HIV. While the study team continues to investigate the potential role of biological and behavioral differences to explain why doxycycline PEP did not work, it is clear that cisgender women need primary STI prevention strategies.

The trial was funded by the National Institutes of Health (R01AI145971, P30AI027757, K23MH124466) and was conducted at the KEMRI Lumumba site in Kisumu, Kenya. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

 

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About Hennepin Healthcare Research Institute
Founded in 1952, Hennepin Healthcare Research Institute (HHRI) supports and administers the medical research conducted at HCMC, the acute care research and teaching hospital of the Hennepin Healthcare System. HHRI supports the work of more than 250 researchers and staff, including MDs, MD/PhDs, PhDs, and PharmDs, and consistently ranks in the top 10 percent of all institutions receiving research funds from the National Institutes of Health. For more information about research at HHRI, visit www.hhrinstitute.org or Twitter @hhrinstitute.