Artificial intelligence system rapidly predicts how two proteins will attach

Antibodies, small proteins produced by the immune system, can attach to specific parts of a virus to neutralize it. As scientists continue to battle SARS-CoV-2, the virus that causes Covid-19, one possible weapon is a synthetic antibody that binds with the virus’ spike proteins to prevent the virus from entering a human cell.

To develop a successful synthetic antibody, researchers must understand exactly how that attachment will happen. Proteins, with lumpy 3D structures containing many folds, can stick together in millions of combinations, so finding the right protein complex among almost countless candidates is extremely time-consuming.

To streamline the process, MIT researchers created a machine-learning model that can directly predict the complex that will form when two proteins bind together. Their technique is between 80 and 500 times faster than state-of-the-art software methods, and often predicts protein structures that are closer to actual structures that have been observed experimentally.

This technique could help scientists better understand some biological processes that involve protein interactions, like DNA replication and repair; it could also speed up the process of developing new medicines.

“Deep learning is very good at capturing interactions between different proteins that are otherwise difficult for chemists or biologists to write experimentally. Some of these interactions are very complicated, and people haven’t found good ways to express them. This deep-learning model can learn these types of interactions from data,” says Octavian-Eugen Ganea, a postdoc in the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL) and co-lead author of the paper.

Ganea’s co-lead author is Xinyuan Huang, a graduate student at ETH Zurich. MIT co-authors include Regina Barzilay, the School of Engineering Distinguished Professor for AI and Health in CSAIL, and Tommi Jaakkola, the Thomas Siebel Professor of Electrical Engineering in CSAIL and a member of the Institute for Data, Systems, and Society. The research will be presented at the International Conference on Learning Representations.

Protein attachment

The model the researchers developed, called Equidock, focuses on rigid body docking — which occurs when two proteins attach by rotating or translating in 3D space, but their shapes don’t squeeze or bend.

The model takes the 3D structures of two proteins and converts those structures into 3D graphs that can be processed by the neural network. Proteins are formed from chains of amino acids, and each of those amino acids is represented by a node in the graph.

The researchers incorporated geometric knowledge into the model, so it understands how objects can change if they are rotated or translated in 3D space. The model also has mathematical knowledge built in that ensures the proteins always attach in the same way, no matter where they exist in 3D space. This is how proteins dock in the human body.

Using this information, the machine-learning system identifies atoms of the two proteins that are most likely to interact and form chemical reactions, known as binding-pocket points. Then it uses these points to place the two proteins together into a complex.

“If we can understand from the proteins which individual parts are likely to be these binding pocket points, then that will capture all the information we need to place the two proteins together. Assuming we can find these two sets of points, then we can just find out how to rotate and translate the proteins so one set matches the other set,” Ganea explains.

One of the biggest challenges of building this model was overcoming the lack of training data. Because so little experimental 3D data for proteins exist, it was especially important to incorporate geometric knowledge into Equidock, Ganea says. Without those geometric constraints, the model might pick up false correlations in the dataset.

Seconds vs. hours

Once the model was trained, the researchers compared it to four software methods. Equidock is able to predict the final protein complex after only one to five seconds. All the baselines took much longer, from between 10 minutes to an hour or more.

In quality measures, which calculate how closely the predicted protein complex matches the actual protein complex, Equidock was often comparable with the baselines, but it sometimes underperformed them.

“We are still lagging behind one of the baselines. Our method can still be improved, and it can still be useful. It could be used in a very large virtual screening where we want to understand how thousands of proteins can interact and form complexes. Our method could be used to generate an initial set of candidates very fast, and then these could be fine-tuned with some of the more accurate, but slower, traditional methods,” he says.

In addition to using this method with traditional models, the team wants to incorporate specific atomic interactions into Equidock so it can make more accurate predictions. For instance, sometimes atoms in proteins will attach through hydrophobic interactions, which involve water molecules.

Their technique could also be applied to the development of small, drug-like molecules, Ganea says. These molecules bind with protein surfaces in specific ways, so rapidly determining how that attachment occurs could shorten the drug development timeline.

In the future, they plan to enhance Equidock so it can make predictions for flexible protein docking. The biggest hurdle there is a lack of data for training, so Ganea and his colleagues are working to generate synthetic data they could use to improve the model.

This work was funded, in part, by the Machine Learning for Pharmaceutical Discovery and Synthesis consortium, the Swiss National Science Foundation, the Abdul Latif Jameel Clinic for Machine Learning in Health, the DTRA Discovery of Medical Countermeasures Against New and Emerging (DOMANE) threats program, and the DARPA Accelerated Molecular Discovery program.

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Precisely opening a gate to the brain in mice

University of Maryland School of Medicine researchers developed a technique in laboratory animals to consistently and reproducibly open the blood-brain barrier. This barrier serves as a barricade securing the brain from the external world blocking out certain environmental toxins, but also prevents drug therapies from reaching their intended targets. The new technique is based on a routine procedure for removing clots from the brain’s arteries in patients. This advancement was conducted by Piotr Walczak, MD, PhD, Professor of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine, and Miroslaw Janowski, MD, PhD, Associate Professor of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine.

The team published their detailed procedure on December 13, 2021, in Nature Protocols. Their paper essentially provides a roadmap for other researchers to develop and test new therapies for brain diseases. The hope is for researchers to use this procedure for treatments against brain cancer, neurological disorders like epilepsy, neurodegenerative diseases like Alzheimer’s and Parkinson’s, or even mental illnesses. The researchers say the technique can potentially be applied in conjunction with the latest medical discoveries, such as genome editing or gene therapy to treat incurable cancers.

The procedure uses magnetic resonance imaging (MRI), which provides feedback in real-time, to control where in the brain the blood-brain barrier gate opens, allowing materials to pass through into spaces that they are normally excluded.

“Scores of interventional radiologists worldwide navigate various sophisticated devices in arteries for standard plumbing tasks in the human brain, like aneurysms or strokes. If there is a leak, they fix it. If there is a clog, they pump it out. This route could be also used to deliver drugs, but the technique had not been perfected in mice and other laboratory animals,” said senior study author Dr. Walczak. “Since most preclinical research starts with mice, it was essential to show how to do this procedure properly in these animals, so scientists across the globe will be able to use it for their drugs to get them to the brain. Some of these drugs will ultimately land in patients as treatments benefiting society.”

Some scientists over the years tried to get drugs into the brains of laboratory animals using other routes such as injecting directly into the brain or the fluid surrounding the brain.

“Researchers had no way of knowing if the drug made it where it was supposed to go at the time of the experiment and some researchers found the procedure unsafe in animals,” said co-author Dr. Janowski, and co-director with Dr. Walczak of the Program in Image-Guided Neurointerventions.

For their specific MRI-guided injection technique, the researchers anesthetized a mouse and surgically inserted the catheter in the neck into the carotid artery that runs to the brain (in people, they use an artery in the groin or hand without requiring surgery). Then, they put the mouse in the MRI machine and performed a scan, while a pump precisely controlled injection speed. To open the blood-brain barrier, the researchers used a solution of mannitol (a type of sugar — a low-cost substance currently used in patients for other treatments) that essentially sucks the liquid out of the cells in blood vessel walls, opening the seals between these cells. Before opening the barrier, they infused gadolinium — a contrast agent used in human medical procedures — through the catheter into the artery, allowing them to see whether the injected material went to its proper destination. If the injection did not work, they adjusted the parameters. Once the conditions were optimized, they opened the barrier in that area of the brain. They used this approach in several other studies targeting biotechnological drugs, such as antibodies, to the brain. Now, the researchers hope their detailed protocol will help other researchers deliver their drug of choice to the brains of their favorite mouse models and eventually help patients.

“Arterial procedures are typically guided using x-ray imaging methods, and that only lets you see the map of the highways in the brain, but these maps are not detailed enough if you needed to go beyond that to the backroads to reach the forest of the brain cells,” said Dr. Janowski. “We believe that by adding MRI, we closed the gap, both in animal studies and in the future in the clinical trials, by providing the necessary level of precision for opening the gate to the brain for the drugs.”

University of Maryland School of Medicine Dean E. Albert Reece, MD, PhD, MBA, who is Executive Vice President for Medical Affairs and the John Z. and Akiko K. Bowers Distinguished Professor, said, “Perfecting basic science techniques like this one are key to laying the groundwork to advancing treatment options for the many diseases of the brain. Sometimes in order to advance clinical research, we have to go back to basics first.”

Additional authors of the study included Post-Doctoral Fellows Chengyan Chu, MD, Yue Gao, MD, and Xiaoyan Lan, MD; Research Associate Anna Jablonska, PhD, Yajie Liang, MD, PhD, Assistant Professor of Diagnostic Radiology and Nuclear Medicine, and Monica Pearl, MD, Adjunct Associate Professor of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine; Wojciech Lesniak, PhD, and Guanshu Liu, PhD, of Johns Hopkins Medicine; Shen Li, MD of Dalian Municipal Central Hospital, China; and Tim Magnus, MD, PhD of University Medical Center Hamburg-Eppendorf, Germany.

This work was funded by the Maryland Stem Cell Research Fund (2017-MSCRFF-3942 and 2019-MSCRFF-5031) and grants from the National Institute of Neurological Disorders and Stroke (R01NS091110, R01NS102675, and R21NS091599).

Dr. Pearl, Dr. Janowski, and Dr. Walczak are founders and equity holders in IntraART. Dr. Janowski and Dr. Walczak are founders and equity holders in Ti-Com.

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How vulnerable to inflation are the finances of older adults?

With consumer prices rising at the fastest pace in almost four decades, older adults face the risk of having their retirement income and savings eaten away by inflation. Richard L. Kaplan is the Guy Raymond Jones Chair in Law at the University of Illinois Urbana-Champaign and an internationally recognized expert on U.S. tax policy and retirement issues. Kaplan spoke with News Bureau business and law editor Phil Ciciora about the harmful effects of inflation on senior citizens’ pocketbooks.

Are retirees adequately protected from inflation through Social Security’s annual cost-of-living adjustment – 5.9% for 2022 – or is the COLA insufficient to offset the inflationary pressures?

Social Security’s cost-of-living adjustment takes some of the sting out of inflation, but not all of it. This adjustment is based on the government’s widely followed Consumer Price Index, but the CPI does not replicate the basket of goods and services that older adults in particular purchase, especially regarding health care costs. Although most of the medical expenses related to COVID-19 have been funded by the federal government, older Americans remain on the hook for other health care costs such as doctor visits, medications and the like – none of which show any signs of moderating. Thus, the increase in Social Security benefits was certainly welcome news to the program’s recipients, but it did not fully offset the effects of inflation as those recipients generally experience it.

If inflation is transitory or weakens in the coming months, would that help retirees come out a little ahead?

It might have that effect, but inflation’s transience is by no means assured. Even if inflation does recede, next year’s cost-of-living adjustment would reflect that change and be smaller as a result. In fact, next year’s adjustment might be eliminated entirely if inflation weakens substantially this year. That has happened in the recent past.

Does the combination of inflation and the rollercoaster stock market underscore the need to strengthen Social Security, especially with COVID-19 increasing the number of new retirees, thereby pushing the program’s insolvency date up a year?

Inflation’s resurgence and the stock market’s renewed volatility certainly unnerve many Social Security recipients, but those phenomena are not exactly new or unexpected. COVID-19, in contrast, is a major development that completely reshuffles many of the program’s components and might make certain structural changes necessary.

On the one hand, many people in their early 60s lost their jobs during the early days of the pandemic or were afraid of returning to their workplaces as different variants emerged. As a result, people who were eligible to begin taking Social Security retirement benefits opted to do so earlier than they might have planned. At the same time, younger people who were paying into the Social Security program also lost their jobs, had their hours reduced or, in some tragic cases, died from the disease. So you have more people taking funds out of Social Security while other people are no longer paying into the program.

On the other hand, the U.S. Census Bureau recently reported that life expectancy in the U.S. declined by 1.8 years, the largest such decline in a very long time. The impact of this decline is that Social Security will be paying lifelong benefits for shorter periods in many cases.

How all this shakes out is hard to tell at this point, but the scope of these different effects may be so significant that various measures that have long been proposed to shore up Social Security’s finances may finally get some serious consideration. We will just have to see.

Editor’s note: To contact Richard L. Kaplan, call 217-300-7973; email rkaplan@illinois.edu.

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Making RNA vaccines easier to swallow

Like most vaccines, RNA vaccines have to be injected, which can be an obstacle for people who fear needles. Now, a team of MIT researchers has developed a way to deliver RNA in a capsule that can be swallowed, which they hope could help make people more receptive to them.

In addition to making vaccines easier to tolerate, this approach could also be used to deliver other kinds of therapeutic RNA or DNA directly to the digestive tract, which could make it easier to treat gastrointestinal disorders such as ulcers.

“Nucleic acids, in particular RNA, can be extremely sensitive to degradation particularly in the digestive tract. Overcoming this challenge opens up multiple approaches to therapy, including potential vaccination through the oral route,” says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital.

In a new study, Traverso and his colleagues showed that they could use the capsule they developed to deliver up to 150 micrograms of RNA — more than the amount used in mRNA Covid vaccines — in the stomach of pigs.

Traverso and Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research, are the senior authors of the study. Alex Abramson PhD ’19 and MIT postdocs Ameya Kirtane and Yunhua Shi are the lead authors of the study, which appears today in the journal Matter.

Oral drug delivery

For several years, Langer’s and Traverso’s labs have been developing novel ways to deliver drugs to the gastrointestinal tract. In 2019, the researchers designed a capsule that, after being swallowed, can place solid drugs, such as insulin, into the lining of the stomach.

The pill, about the size of a blueberry, has a high, steep dome inspired by the leopard tortoise. Just as the tortoise is able to right itself if it rolls onto its back, the capsule is able to orient itself so that its contents can be injected into the lining of the stomach.

In 2021, the researchers showed that they could use the capsule to deliver large molecules such as monoclonal antibodies in liquid form. Next, the researchers decided to try to use the capsule to deliver nucleic acids, which are also large molecules.

Nucleic acids are susceptible to degradation when they enter the body, so they need to be carried by protective particles. For this study, the MIT team used a new type of polymeric nanoparticle that Langer’s and Traverso’s labs had recently developed.

These particles, which can deliver RNA with high efficiency, are made from a type of polymer called poly(beta-amino esters). The MIT team’s previous work showed that branched versions of these polymers are more effective than linear polymers at protecting nucleic acids and getting them into cells. They also showed that using two of these polymers together is more effective than just one.

“We made a library of branched, hybrid poly(beta-amino esters), and we found that the lead polymers within them would do better than the lead polymers within the linear library,” Kirtane says. “What that allows us to do now is to reduce the total amount of nanoparticles that we are administering.”

To test the particles, the researchers first injected them into the stomachs of mice, without using the delivery capsule. The RNA that they delivered codes for a reporter protein that can be detected in tissue if cells successfully take up the RNA. The researchers found the reporter protein in the stomachs of the mice and also in the liver, suggesting that RNA had been taken up in other organs of the body and then carried to the liver, which filters the blood.

Next, the researchers freeze-dried the RNA-nanoparticle complexes and packaged them into their drug delivery capsules. Working with scientists at Novo Nordisk, they were able to load about 50 micrograms of mRNA per capsule, and delivered three capsules into the stomachs of pigs, for a total of 150 micrograms of mRNA. This is the more than the amount of mRNA in the Covid vaccines now in use, which have 30 to 100 micrograms of mRNA.

In the pig studies, the researchers found that the reporter protein was successfully produced by cells of the stomach, but they did not see it elsewhere in the body. In future work, they hope to increase RNA uptake in other organs by changing the composition of the nanoparticles or giving larger doses. However, it may also be possible to generate a strong immune response with delivery only to the stomach, Abramson says.

“There are many immune cells in the gastrointestinal tract, and stimulating the immune system of the gastrointestinal tract is a known way of creating an immune response,” he says.

Immune activation

The researchers now plan to investigate whether they can create a systemic immune response, including activation of B and T cells, by delivering mRNA vaccines using their capsule. This approach could also be used to create targeted treatments for gastrointestinal diseases, which can be difficult to treat using traditional injection under the skin.

“When you have systemic delivery through intravenous injection or subcutaneous injection, it’s not very easy to target the stomach,” Abramson says. “We see this as a potential way to treat different diseases that are present in the gastrointestinal tract.”

Novo Nordisk, which partially funded the research, has licensed the drug-delivery capsule technology and hopes to test it in clinical trials. The research was also funded by the National Institutes of Health, the National Science Foundation Graduate Research Fellowships Program, a PhRMA Foundation postdoctoral fellowship, the Division of Gastroenterology at Brigham and Women’s Hospital, and MIT’s Department of Mechanical Engineering.

Other authors of the paper are Grace Zhong, Joy Collins, Siddartha Tamang, Keiko Ishida, Alison Hayward, Jacob Wainer, Netra Unni Rajesh, Xiaoya Lu, Yuan Gao, Paramesh Karandikar, Chaoyang Tang, Aaron Lopes, Aniket Wahane, Daniel Reker, Morten Revsgaard Frederiksen, and Brian Jensen.

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Green shoots for a greying countryside

Most farm managers in Europe are nearing retirement. There is a need to revitalise rural areas in Europe and crate opportunities for younger people. Social scientists are scrutinising the problem of rural decline, highlighting success stories and policy actions and tracking paths back to a more prosperous countryside. 

Farming is an ancient profession. But a problem in Europe is that the farmers themselves are getting old. From the more than ten million farm managers, one-third were over the age of 65 in 2016. Another one-quarter were 55 and over, while only 11% were under 40 years of age.

It is clear that rural areas need to halt population declines and attract new generations. To turn back the tide and regenerate rural areas, social scientists are unearthing how and why some rural areas are growing and performing better than others.

This will reveal how farming can seed a new crop of young farmers, as well as encourage green shoots in rural communities, and transform them into more attractive places to live and work.

‘Farmers are getting old and mostly male. About 13% of farmland is managed by female farmers,’ said Willem Korthals Altes, land development professor at TU Delft in the Netherlands. ‘There is also an issue of declining rural regions, and this all needs new policies.’

Specifically, Professor Korthals Altes has examined the aspirations of young people in rural and urban areas in 12 different countries and looked at what actions could be taken to attract newcomers to the countryside as part of the four-year EU-wide RURALIZATION research project. Prof. Korthals Altes and his team have interviewed about 2,000 young people in 20 regions of the EU about their hopes for the future. One surprise was that many people, in cities and the countryside, would like to live in rural areas, often for quality-of-life reasons.

The project aims to identify paths to overcome population and economic decline in rural Europe and seed new opportunities. Right now, the picture painted by statistics is bleak. The EU lost 11% of its farmland between 1993 and 2013, while farms themselves are getting bigger and fewer, which contributes to job losses.  ‘If we look at just the overall statistics, what we found is sad,’ said Prof. Korthals Altes.  ‘So we looked for positive examples that we could learn from and also highlight positive practices.’

Specific case studies have been published, such as an agro-tourism farm in rural Poland set up by newcomers from Warsaw to grow organic crops and run ecological workshops, a community-owned farms group in the Netherlands and a silkworm farm with mulberry trees in Italy.

Growing trends and recommendations

Rural trends identified in the project included a rise in alternative food systems such as organic farming due to greater environmental awareness.  There were also evolving gender roles in private and working life and diversification of farm business and diversification of rural economies. Two other trends were digitisation of economic activity and the rise of online markets, which can open the gate to new business opportunities in rural regions.

Newcomers into rural areas may be especially important for economic revival, because of their higher education, wider network of contacts and tendency to innovate, the study found.  It also revealed that organic production has increased significantly in most countries, and that this is one of the most important alternative forms of renewal.

The “young farmer problem” is more marked in some countries than others. Just 3.3% of farm managers in Cyprus and 4.2% in Portugal are under 40, while the figure is closer to 20% in Poland and Slovakia. The problems in one country do not match exactly those in another.

But one common barrier for new entrants to agriculture is access to land, and there is a lack of policies to support people who want to begin farming. ‘We find policies related to the modernisation agenda of farming, but not much about new entrants to farming,’ said Prof Korthals Altes. The project reported on some 64 access to land practices, from partners to the project, that can contribute to rural generation.

No EU Member States have elaborate policies and legal arrangements for providing access to land, says Korthals Altes. ‘The per hectare direct payments that a farmer gets for holding the land in good agricultural condition are in most EU regions higher than the rent, which works out negatively for new entrants,’ notes Korthals Altes. ‘It is a better retirement plan to keep your land with the direct payments, than to rent it out to new farmers.’ Nonetheless, under changes to the new Common Agricultural Policy announced last December, there will be additional support for young farmers’ income, such as national authorities having to direct 2% of local income support to them and young farmers being prioritised to receive basic payments.

Korthals Altes now plans discussions with stakeholders and for the project to draw up recommendations for rural renewal that local governments and agencies can tap into.

The most obvious recommendation is to make a future in agriculture attractive to young farmers and new entrants. However, a lack of interest among young people to work in the farming sector is a common phenomenon for developed economies, and many don’t look on farming as a prestigious career option, according to Dr İlkay Unay-Gailhard at the Leibniz Institute of Agricultural Development in Germany.  ‘When we ask the young people about their image of farming, they state its low income, hard physical work and low prestige,’ she explained.

No lack of interest

But this should not be misunderstood as a lack of interest in agriculture, as seen in the frequent protests by young people against industrial farming practices.  ‘We know digital communications influence the social behaviour of young people and they show more support for ecological farming,’ said Dr Unay-Gailhard.  ‘But we don’t know how they influence their choice of farming as a career option.’

Awarded an EU Marie Sklodowska-Curie Global Fellowship for her a research project Young Farmers, she will interview dozens of young farmers in the US and in Germany about their personal history and about how digital communication messages influenced their career option.  She believes that there is a lack of positive role model images of farmers, and absence of “farmer and mother” as a role model in family farms.

Dr Unay-Gailhard will also talk to government agencies and non-profit organisations about the use of new media tools – such as interactive online portals, blogs, online agricultural communication and public engagement campaigns and social media services – to assist those at the start of their career and those who might transition towards farming. Career paths are no longer as planned and predictable, and career trajectories can change course. ‘Young people these days can follow rising opportunities,’ said Dr Unay-Gailhard.

Also, how farms are run is shifting. Advanced digital technologies and robotics are making inroads on some farms, and young farmers may be motivated by the more high-tech, innovative approaches to farming.

Dr Unay-Gailhard will recommend to government agencies and farm organisations ways to communicate digitally with young people.  The hope is that young people will have better access to information on agricultural careers, and reconsider the benefits on offer from a rural career and lifestyle.

The research in this article was funded by the EU. If you liked this article, please consider sharing it on social media.

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‘Fitbit for the face’ can turn any face mask into smart monitoring device

Northwestern University engineers have developed a new smart sensor platform for face masks that they are calling a “Fitbit for the face.”

Dubbed “FaceBit,” the lightweight, quarter-sized sensor uses a tiny magnet to attach to any N95, cloth or surgical face mask.

Not only can it sense the user’s real-time respiration rate, heart rate and mask wear time, it also may be able to replace cumbersome tests by measuring mask fit. All this information is then wirelessly transmitted to a smartphone app, which contains a dashboard for real-time health monitoring. The app can immediately alert the user when issues — such as elevated heart rate or a leak in the mask — unexpectedly arise. The physiological data also could be used to predict fatigue, physical health status and emotional state.

Although a tiny battery powers the device, FaceBit is designed to harvest energy from any variety of ambient sources — including the force of the user’s breathing, motion and heat from a user’s breath as well as from the sun. This extends the sensor’s battery life, lengthening time between charges.

“We wanted to design an intelligent face mask for health care professionals that does not need to be inconveniently plugged in during the middle of a shift,” said Northwestern’s Josiah Hester, who led the device development. “We augmented the battery’s energy with energy harvesting from various sources, which means that you can wear the mask for a week or two without having to charge or replace the battery.”

The research was published last week in the Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies. In the study, researchers found FaceBit’s accuracy was similar to clinical-grade devices, and the battery lasted longer than 11 days between charges. More information is available at facebit.health.

Hester is an assistant professor of computer science, computer engineering and electrical engineering and the Breed Junior Professor of Design at Northwestern’s McCormick School of Engineering.

Approximating the fit test

Before designing FaceBit, Hester and his collaborators first interviewed doctors, nurses and medical assistants to better understand their needs for smart face masks. In a series of surveys, all clinicians indicated that quality of mask fit was most important — especially when working directly with patients with viral infections.

To ensure their N95 masks are properly sealed to their faces, health care workers periodically undergo a 20-minute “fit test.” During this process, health care workers first put on an N95 respirator followed by a clear hood over their entire head. Another worker then pumps either sweet or bitter aerosol mists into the hood. The concentration of the aerosol is gradually increased inside the hood until it can be detected by the person wearing the respirator. If the wearer tastes bitter or sweet before a certain number of aerosol pumps, then the mask is not properly sealed.

 

If you wear a mask for 12 hours or longer, sometimes your face can become numb. You might not even realize that your mask is loose because you cannot feel it.”

Josiah Hester
computer engineer

 

Although Hester’s FaceBit cannot yet replace this cumbersome process — which is a long-standing challenge in the medical industry — it can ensure the mask retains proper fit between testing events. If the mask becomes loose throughout the day or if the user bumps the mask during an activity, for example, FaceBit can alert the wearer.

“If you wear a mask for 12 hours or longer, sometimes your face can become numb,” Hester said. “You might not even realize that your mask is loose because you cannot feel it or you are too burnt out to notice. We can approximate the fit-testing process by measuring mask resistance. If we see a sudden dip in resistance, that indicates a leak has formed, and we can alert the wearer.”

Face-centric bio-sensing

But the FaceBit can assess more than mask fit — it also can monitor the person wearing the mask in real time. By gathering various physiological signals — such as heart and respiratory rates — FaceBit can help wearers better understand their own bodies in order to make beneficial health decisions. All health information, including mask fit and wear time, are displayed on the accompanying smartphone app.

According to Hester, every time a person’s heart beats, their head moves an imperceptibly tiny amount. FaceBit can sense that subtle motion — and differentiate it from other motions — in order to calculate heart rate.

“Your heart is pushing a lot of blood through the body, and the ballistic force is quite strong,” Hester said. “We were able to sense that force as the blood travels up a major artery to the face.”

Because stressful events can elicit physiological responses, including rapid breathing, FaceBit can use that information to alert the user to take a break, go for a walk or take some deep breaths to calm down. Hospital systems also could use this data to optimize shift and break schedules for its workers. And because heart rate and respiration rate are so tightly entangled with each other, having the ability to effortlessly monitor both could open new research possibilities.

Battery-free future

An expert in sustainable, battery-free technology, Hester hopes his team or others eventually will be able to make FaceBit completely battery free. Now, the wearer’s breathing and movements or the sun can extend the battery’s life. But, in the future, harvested thermal and kinetic energy could solely power the device.

Although his team evaluated the device on volunteers in real-world scenarios, Hester said FaceBit still needs to undergo clinical trials and validation. The team released the project as open source and open hardware so others can build and validate the device.

“FaceBit provides a first step toward practical on-face sensing and inference, and provides a sustainable, convenient, comfortable option for general health monitoring for COVID-19 frontline workers and beyond,” Hester said. “I’m really excited to hand this off to the research community to see what they can do with it.”

The project, “FaceBit: Smart Face Masks Platform,” was supported by the National Science Foundation’s Grants for Rapid Response Research for addressing the COVID-19 pandemic (award number CNS-2032408). FaceBit was a collaboration with Nabil Alshurafa, assistant professor of preventative medicine in Northwestern University Feinberg School of Medicine and of computer science in McCormick.

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Live cells discovered in human breast milk could aid breast cancer research

Researchers have explored the cellular changes that occur in human mammary tissue in lactating and non-lactating women, offering insight into the relationship between pregnancy, lactation, and breast cancer.

The study was led by researchers from the Wellcome-MRC Cambridge Stem Cell Institute (CSCI) and the Department of Pharmacology at the University of Cambridge.

Breast tissue is dynamic, changing over time during puberty, pregnancy, breastfeeding, and aging. The paper, published today in the journal Nature Communications, focuses on the changes that take place during lactation by investigating cells found in human milk.

This research, led by Dr Alecia-Jane Twigger of CSCI, found that the cells in milk, once thought to be dead or dying, are in fact very much alive. These living cells provide researchers with the chance to study not only the changes that occur in mammary tissues during lactation, but also insight into a potential early indicator of future breast cancer development.

“I believe that by studying human milk cells, we will be able to answer some of the most fundamental questions around mammary gland function such as: how is milk produced? Why do some women struggle to make milk? and what strategies can be employed to improve breastfeeding outcomes for women?” said Dr Alecia-Jane Twigger at the Wellcome-MRC Cambridge Stem Cell Institute who led the study.

The researchers collected voluntary breast milk samples from lactating women, as well as samples of non-lactating breast tissue donated from women who elected to have aesthetic breast reduction surgery. Using single-cell RNA sequencing analysis, the team conducted a novel comparison of the composition of the mammary cells taken using these two methods, identifying the distinctions between lactating and non-lactating human mammary glands.

While accessing breast tissue for study relies on donors already undergoing surgery, breast milk samples are much simpler to acquire. Breast milk donors are engaged via midwives or women’s networks (an undertaking made more challenging by the pandemic) and agree to share their samples over time. Typical daily production for lactating women is between 750-800ml, and the sample size for Twigger’s research is on average a mere 50ml, an amount which can contain hundreds of thousands of cells for study.

By collecting these samples donated by breastfeeding women – samples now known to contain living and viable cells – researchers have the opportunity to capture dynamic cells in a non-invasive way. This greater ease of access to breast cells can open the door to more studies on women’s health in the future.

“The first time Alecia told me that she found live cells in milk I was surprised and excited about the possibilities. We hope this finding will enable future studies into the early steps of breast cancer,” said Dr Walid Khaled, at the Wellcome-MRC Cambridge Stem Cell Institute and University of Cambridge’s Department of Pharmacology, who was also involved in the study.

This paper and its findings are part of the Human Breast Cell Atlas project funded by the MRC.

This research was funded by the MRC, BBSRC and Wellcome-MRC Cambridge Stem Cell Institute.

Reference: Twigger, A., et al.: ‘Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk.’ Nature Communications, Jan 2022. DOI: 10.1038/s41467-021-27895-0

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Microbes help hibernating animals recycle nutrients, maintain muscle through winter

To get through a long winter without food, hibernating animals — like the 13-lined ground squirrel — can slow their metabolism by as much as 99 percent, but they still need important nutrients like proteins to maintain muscles while they hibernate. A new study from the University of Wisconsin–Madison shows that hibernating ground squirrels get help from microbes in their guts.

The discovery could help people with muscle-wasting disorders and even astronauts on extended space voyages.

“The longer any animal doesn’t exercise, bones and muscles start to atrophy and lose mass and function,” says Hannah Carey, an emeritus professor in the UW–Madison School of Veterinary Medicine and co-author of the new study, published today (Jan. 27) in the journal Science. “Without any dietary protein coming in, hibernators need another way to get what their muscles need.”

One source of nitrogen, a vital building block for amino acids and proteins, accumulates in the bodies of all animals (including humans) as urea, a component of urine. The researchers knew that urea that moved into the squirrels’ digestive tract could be broken down by some gut microbes, which also need nitrogen for their own proteins. But the researchers wanted to see if some of that urea nitrogen freed up by the microbes was also being incorporated into the squirrels’ bodies.

They injected urea made with trackable isotopes of carbon and nitrogen into the blood of squirrels at three stages — during the active days of summer, early in winter hibernation and late in winter. Some of the squirrels had also been treated with antibiotics to kill off the majority of the microbes in their intestines. As predicted, isotope-containing nitrogen was released by some of the gut microbes that degraded the injected urea.

“We followed that nitrogen to (the) livers (of the squirrels), primarily — where it is used to make many proteins — and some to muscles,” says study co-investigator Fariba Assadi-Porter, an UW–Madison emeritus biochemist who specializes in tracking the isotopes. She is also a scientist in Integrative Biology and the university’s Nuclear Magnetic Resonance Facility. “We believe we’re seeing the isotope-labeled nitrogen molecules go from the host to the microbiome, then converted to usable molecules by the microbes before coming back to the host again, essentially being ‘recycled’ in the hibernating animal.”

The researchers observed two differences that support this microbial path. The squirrels whose gut microbes were largely depleted by antibiotics had far less of the trackable nitrogen in their liver and muscles. And when the researchers sequenced the genomes of microbes found in the squirrels’ guts, they found that as winter hibernation dragged on there was an increase in the presence of genes related to production of an enzyme called urease.

“Urease is not made by animals. Only microbes that express urease are able to split the urea molecule and release its nitrogen,” says Carey, whose work is supported by the National Science Foundation. “As long as the right microbes are present, it’s a transaction between them and the host — each get some of the nitrogen released to tide them over until hibernation ends.”

Describing the keys to survival over the duration of hibernation could help people on low-nitrogen diets or with disorders that cause muscles to atrophy. It could also make it possible for humans to make lengthy trips to distant planets.

Putting space travelers into a hibernation-like state means they wouldn’t need to take as much food, water and oxygen, and would produce less waste and carbon dioxide, saving vast amounts of weight and fuel.

“This process could theoretically reduce rates of muscle loss in space, where microgravity exposure invariably leads to muscle atrophy,” says Matthew Regan, a study co-author and former UW–Madison postdoctoral researcher who is now a professor of animal physiology at the University of Montreal. “And because characteristics of hibernation beyond this gut microbe-dependent process confer protection against other hazards of space flight such as ionizing radiation, it is theoretically possible that, if translated to humans, hibernation-like states could solve numerous challenges of human spaceflight simultaneously.”

This research was funded by grants from the National Science Foundation (IOS-1558044 and DGE-1747503), the National Institutes of Health (P41GM136463, P41GM103399, P41RR002301 and T32GM008349) and the Natural Sciences and Engineering Research Council of Canada.

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UCF to Lead $10M NASA Project to Develop Zero-Carbon Jet Engines

UCF is developing new technology that is expected to make airplane engines emission free, potentially revolutionizing the aviation industry.

UCF put together a team of experts and stakeholders to evaluate their innovation, which aims to not only make aviation fuel green, but also create engines and fueling systems that easily integrate into current airport infrastructure thus saving airports and aircraft manufacturers millions of dollars as they look to retrofit.

“We don’t want to create something that will be too cumbersome and expensive to implement,” says lead investigator and UCF Engineering Professor Jay Kapat. “If we want people to adopt this green tech, it needs to be scalable. To adopt hydrogen, for example, we can’t expect every airport to set up large cryogenic liquid hydrogen systems like Kennedy Space Center. That’s unreasonable.”

With this practical approach, Kapat put together a team of experts from UCF, Georgia Tech and Purdue and with industry experts from Boeing, General Electric, ANSYS, Southwest Research Institute and the Greater Orlando Aviation Authority. The team landed a $10 million five-year NASA University Leadership Initiative grant to get the ball rolling.

“We have a good concept,” Kapat says. “And by having our partners in industry we know we’ll fine tune and be ready for technology transition, so we can provide a greener future for our children.”

The Tech

Kapat and several of his UCF colleagues in engineering and the Florida Space Institute propose using liquid ammonia (NH₃) as the fuel for aircraft which, upon combustion, will produce harmless emissions that are green while still providing enough power to keep the aircraft aloft. At high altitudes ammonia is naturally liquid thereby limiting the need for special handling. Airports and airplanes are expected to store the ammonia in fuel tanks. Ammonia is commonly used as a fertilizer and, when mixed with water, in some household cleaners.

Ammonia will be the hydrogen carrier, which will be catalytically “cracked” to release nitrogen and hydrogen. The hydrogen will be burned in the onboard combustors (inside the engine) to provide the power. Airports and aircraft are expected to store the NH₃ in fuel tanks. Excess NH₃ will then be used to catalytically reduce any NO_x left in the exhaust converting it to nitrogen and water.

When the hydrogen is released, there will be an added bonus, Kapat explained. The conversion process also provides cooling, which can be used to keep engines from overheating and burning out. The impact may be better engine performance and efficiency. Engine exhaust heat is then converted back to electricity for onboard use, thus reducing power draw from the core engines.

The team also is developing new components for jet engines to be used in conjunction with the new fuel. The team is using the 737-8 class for a baseline as it represents nearly a quarter of all commercial aircraft, according to Boeing.

The Team

“This project would not have been possible without our internal and external partners,” Kapat says.

Catalyst development and improvement of known catalysis pathways are key to the UCF effort and will be undertaken in Professor Richard Blair’s laboratory at the Florida Space Institute. Engineering Professor Subith Vasu will lead the efforts to design tools, computer models, and combustion testing from his lab. Professor Kapat will lead a team that will conduct thermal management and system integration at UCF’s Center for Advanced Turbomachinery and Energy Research (CATER), which he leads. UCF Chemical Safety and Security Coordinator Sandra Hick will oversee safety and occupational health issues that are central to any use of ammonia and hydrogen.

Georgia Tech will provide its aviation simulation expertise and Purdue is providing some of its unique labs and expertise in combustion and aerodynamics. Boeing is providing the integration know-how to the aircraft, and GE is contributing its knowledge of the jet engines. Other industry partners are advising on large scale simulation, the feasibility of the technology in the real world and providing a pathway for technology transition. Student training and workforce development are also key aspects of the overall project. Several UCF students working under faculty in the various labs will contribute to the research.

The UCF team includes:

• Vasu, an expert in spectroscopy, propulsion combustion and optical diagnostics
• Blair, an expert in energy efficient catalytic processing of bio-derived compounds for fuels and chemical feedstock
• Hick, chemical safety and security coordinator for UCF Environmental Health and Safety.
• Hans-Jürgen Kiesow, a courtesy professor in CATER at UCF. A retired Siemens vice president who over saw gas turbines design and development, and management of complex global teams.
• Erik Fernandez, a research assistant professor in Engineering
• Ladislav Vesely and Marcel Otto, post-doctoral scholars funded in part by UCF’s Preeminent Scholar’s program

Other collaborators are:

• Terrence Meyer, Guillermo Paniagua form Purdue University
• Dimitri Marvis and Jonathan Gladin from Georgia Institute of Technology
• Greg Natsui, ’10 ’12 MS ’15PhD and Keith McManus from GE
• Michael Stoia, Kevin Jui and Nickolas Applegate from Boeing
• Swati Saxena from ANSYS
• Joshua Schmitt ‘15MS, Tim Allison and Grant Musgrove from the Southwest Research Institute
• Kevin Thompson from the Greater Orlando Aviation Authority.

Kapat is recognized expert in energy research.  He leads CATER, which has brought together experts who are solving some of the most complex research problems in turbomachinery for power generation, aviation, and space propulsion. Kapat has multiple degrees including a doctorate in mechanical engineering from Massachusetts Institute of Technology. He is a Fellow of the American Society of Mechanical Engineers, and an American Institute of Aeronautics and Astronautics Associate fellow. He joined UCF in 1997 and has published more than 350 articles, many of which are highly cited by researchers around the world.

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Rethinking cooking with gas

Humans have cooked with fire for millennia, but it may be time for a change. Natural gas appliances warm the planet in two ways: generating carbon dioxide by burning natural gas as a fuel and leaking unburned methane into the air. A new Stanford-led study reveals that the methane leaking from natural gas-burning stoves inside U.S. homes has a climate impact comparable to the carbon dioxide emissions from about 500,000 gasoline-powered cars.

This extra warming from home methane leaks contributes about a third as much warming as the carbon dioxide generated by combustion of the stove’s natural gas, and sometimes exposes users to respiratory disease-triggering pollutants. The findings, published in Environmental Science & Technology, come as legislators in numerous U.S. municipalities and at least one state – New York – weigh banning natural gas hookups from new construction.

“Surprisingly, there are very few measurements of how much natural gas escapes into the air from inside homes and buildings through leaks and incomplete combustion from appliances,” said study lead author Eric Lebel, who conducted the research as a graduate student in Stanford’s School of Earth, Energy and Environmental Sciences (Stanford Earth). “It’s probably the part of natural gas emissions we understand the least about, and it can have a big impact on both climate and indoor air quality.”

An overlooked contributor to a growing problem

Although carbon dioxide is more abundant in the atmosphere, methane’s global warming potential is about 86 times as great over a 20-year period and at least 25 times as great a century after its release. Methane also threatens air quality by increasing the concentration of tropospheric ozone, exposure to which causes an estimated 1 million premature deaths annually worldwide due to respiratory illnesses. Methane’s relative concentration has grown more than twice as fast as that of carbon dioxide since the beginning of the Industrial Revolution because of human-driven emissions.

While pipeline leaks of natural gas, which is more than 90 percent methane, have been studied extensively, natural gas-burning cooking appliances have received comparatively little attention.

Over one-third of U.S. households – more than 40 million homes – cook with gas. Unlike other gas appliances, such as space and water heaters that are usually placed away from living quarters, cooking appliances directly expose people to their emissions, which can include formaldehyde, carbon monoxide and nitric oxides that can trigger asthma, coughing, wheezing and difficulty breathing, occasionally resulting in hospitalization. Hood use and ventilation help reduce concentrations of nitrogen oxides and other co-produced pollutants in kitchen air, yet surveys show that home cooks on average use hoods for kitchen ventilation only 25–40 percent of the time.

Findings and implications

To better understand cooking appliances’ potential climate and health impacts, the researchers measured methane and nitrogen oxides released in 53 homes in California, not only during combustion, ignition and extinguishment, but also while the appliance was off, something most previous studies had not done. Their study included 18 brands of gas cooktops and stoves ranging in age from 3 to 30 years.

The highest emitters were cooktops that ignited using a pilot light instead of a built-in electronic sparker. Methane emissions from the puffs of gas emitted while igniting and extinguishing a burner were on average equivalent to the amount of unburned methane emitted during about 10 minutes of cooking with the burner. Interestingly, the researchers found no evidence of a relationship between the age or cost of a stove and its emissions. Most surprising of all, more than three-quarters of methane emissions occurred while stoves were off, suggesting that gas fittings and connections to the stove and in-home gas lines are responsible for most emissions, regardless of how much the stove is used.

Overall, the researchers estimated that natural gas stoves emit up to 1.3 percent of the gas they use as unburned methane. While the U.S. Environmental Protection Agency (EPA) does not report emissions from specific residential natural gas appliances, it does report methane emissions for residential appliances collectively. From stoves alone, the researchers estimated total methane emissions to be substantially more than the emissions currently reported by the EPA for all residential sources.

Larger stoves tended to emit higher rates of nitric oxides, for example. Using their estimate of emissions of nitrogen oxides, the researchers found that people who don’t use their range hoods or who have poor ventilation can surpass the EPA’s guidelines for 1-hour exposure to nitrogen dioxide outdoors (there are no indoor standards) within a few minutes of stove usage, particularly in smaller kitchens.

“I don’t want to breathe any extra nitrogen oxides, carbon monoxide or formaldehyde,” said study senior author Rob Jackson, the Michelle and Kevin Douglas Provostial Professor and professor of Earth system science. “Why not reduce the risk entirely? Switching to electric stoves will cut greenhouse gas emissions and indoor air pollution.”

Jackson is also a senior fellow at the Stanford Woods Institute for the Environment and the Precourt Institute for Energy. Lebel is currently a senior scientist at PSE Healthy Energy. Study co-authors also include Colin Finnegan, an environmental science research professional in Earth system science, and Zutao Ouyang, a postdoctoral scholar in Earth system science.

To read all stories about Stanford science, subscribe to the biweekly Stanford Science Digest.

Media Contacts

Eric Lebel, School of Earth, Energy & Environmental Sciences: (510) 863-8497, elebel@psehealthyenergy.org

Rob Jackson, School of Earth, Energy & Environmental Sciences: (650) 497-5841, rob.jackson@stanford.edu

Rob Jordan, Stanford Woods Institute for the Environment: (650) 721-1881, rjordan@stanford.edu

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Mix-and-match trial finds additional dose of COVID-19 vaccine safe, immunogenic

In adults who had previously received a full regimen of any of three COVID-19 vaccines granted Emergency Use Authorization (EUA) or approved by the U.S. Food and Drug Administration, an additional booster dose of any of these vaccines was safe and prompted an immune response, according to preliminary clinical trial results reported in The New England Journal of Medicine. The findings served as the basis for recommendations by the FDA and the Centers for Disease Control and Prevention in late fall 2021 to permit mix-and-match COVID-19 booster vaccinations in the United States. Additional data from the ongoing Phase 1/2 trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, are expected in the coming months.

The new report describes findings from 458 adults who had been fully vaccinated with any of three EUA COVID-19 vaccines at least 12 weeks prior to enrollment and who had no reported history of SARS-CoV-2 infection. At enrollment, a single booster dose was administered to each participant: 150 received Janssen/Johnson & Johnson’s Ad26.COV2.S vaccine; 154 received Moderna’s mRNA-1273 vaccine; and 154 received Pfizer-BioNTech’s BNT162b2 vaccine. Depending on which primary vaccine regimen a participant had received, the booster vaccine was either different (mixed, or heterologous) than or the same (matched, or homologous) as the original vaccine.

The trial participants kept diaries of any side effects. More than half of participants reported headache, pain at the injection site, muscle aches and malaise. No serious vaccine-related adverse events were reported.

All combinations of primary and booster vaccine resulted in increased neutralizing antibody levels (ranging from 4.2- to 76-fold higher levels than those detected prior to boost.) Likewise, all primary-boost combinations increased binding antibody levels 4.6- to 56-fold. For each primary EUA COVID-19 vaccine, heterologous boosts elicited similar or higher antibody responses as compared to responses to a homologous booster. Cellular responses (CD4 and CD8 T cell) also increased in all but the homologous Ad26.CoV2.S-boosted group, though CD8+ T cells were highest at baseline in those participants who had received the Ad26.CoV2.S EUA vaccine.

Taken together, the investigators concluded, these data strongly suggest that homologous and heterologous booster vaccine will increase protective efficacy against symptomatic SARS-CoV-2 infection.

These interim results cover available immunogenicity data through the initial 29 days following booster vaccination. Investigators will continue to follow participants for one year to assess what impact booster vaccination has on longer-term immune responses. Additional arms of the trial may test other investigational, EUA or FDA-approved COVID-19 vaccines and/or vaccines based on SARS-CoV-2 variants as the boosting vaccine.

The trial began in May 2021 and is continuing to enroll participants. Its principal investigators are Robert L. Atmar, M.D., of Baylor College of Medicine, Houston; and Kirsten E. Lyke, M.D., of the University of Maryland School of Medicine, Baltimore. It is being conducted through NIAID’s Infectious Diseases Clinical Research Consortium, a clinical trials network that encompasses the Institute’s longstanding Vaccine and Treatment Evaluation Units (VTEUs). Additional information about the trial, including a listing of trial sites enrolling volunteers, is available at ClinicalTrials.gov using the identifier NCT04889209.

NIAID grants supporting this research were UM1AI48372, UM1AI148373, UM1AI148450, UM1AI148452, UM1AI148573, UM1AI148574, UM1AI148575, UM1AI148576, UM1AI148684 and UM1AI148689. Contract 75N93019C00050 from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) also provided support.

Article 

RL Atmar et al. Homologous and heterologous COVID-19 booster vaccinations. The New England Journal of Medicine DOI: 10.1056/NEJMoa2116414 (2022).

Who

Dr. John H. Beigel, associate director for clinical research in NIAID’s Division of Microbiology and Infectious Diseases, is available to discuss the study.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Connection to racial identity may boost body image in Black youth

Adolescence can be a time filled with anxiety and insecurity about body shape and size, but a new Penn State study found that for Black youth, having a strong racial identity may help stave off these worries.

The researchers found that among Black youth between the ages of 11 and 19 with high body mass indexes (BMI), those who reported a strong sense of racial identity also reported fewer weight concerns. This was true for both girls and boys.

The participants’ sense of racial identity was measured by how much they agreed with statements like “I am happy that I am Black/African American/ part Black/African American.”

Anna Hochgraf, graduate student in the department of Human Development and Family Studies (HDFS) at Penn State, said the findings provide insights into how race may affect body image.

“Compared to individuals from other racial groups in the U.S., some evidence suggests that Black girls and women have an ideal of beauty that features curvy body shapes and larger body sizes,” Hochgraf said. “For Black youth with overweight, racial identity may be protective against weight concerns because it promotes appreciation of larger body size and corresponding pride in appearance.”

The researchers also found that the more fathers were involved in teaching their daughters about Black culture, the less likely their daughters were to report harmful weight concerns.

Adenique Lisse, research assistant at the Child Mind Institute and a former HDFS undergraduate and Schreyer Honors student at Penn State, said that taken together, results could inform prevention and intervention strategies designed to address weight concerns.

“Services that incorporate strategies for strengthening youth racial identity and promoting parents’ racial socialization may be beneficial for Black youth,” Lisse said. “Additionally, our findings about racial socialization suggest the importance of involving fathers of daughters as much as possible.”

The results were recently published in the Journal of Research on Adolescence.

According to previous research, concerns about weight often emerge during adolescence and affect approximately 78% of adolescent girls and 60% of adolescent boys. Other research found that these concerns can lead to poorer mental and physical health, such as low self-esteem, depressive symptoms and eating disorders.

“The term ‘weight concerns’ is used by researchers to refer to worries about body shape and weight, perceptions of having overweight, overemphasis of the importance of body weight and shape, and dieting behaviors,” Hochgraf said. “Weight concerns are not healthy — they can lead to eating disorders and other psychological and physical health problems.”

But, as Lisse noted, the majority of prior research on weight concerns focused on white adolescents and less was known about weight concerns among Black youth. Because racial orientations such as cultural values and racial identity can help shape beauty ideals, the researchers decided to explore how these factors might affect Black adolescents.

“Parents encouraging their children to embrace their culture and promote their pride in being Black may help them become resilient against majority culture messages about the ‘thin ideal’ of beauty,” Lisse said, “Such parenting may also protect heavier Black youth from developing unhealthy feelings about weight. Plus, racial socialization may help form Black youths’ body images and foster appreciation of body sizes that do not conform to the ‘thin ideal.’”

For the study, the researchers recruited 132 two-parent families who self-identified as Black or African American. The participants — mothers, fathers and youth — were interviewed at the beginning of the study and again a year later.

At both points in time, the researchers measured adolescents’ BMIs and asked them about their weight concerns, such as “how afraid are you of gaining three pounds?” They also asked questions about their racial identities — for example, “I have a clear sense of being Black, African American, or part Black/African American and what that means for me.”

The researchers also asked parents about how often they engaged in cultural socialization with their child, for example, “I’ve read or provided Black history books to my child.”

Hochgraf noted that although they found that fathers’ but not mothers’ racial socialization was associated with fewer weight concerns among girls, mothers’ racial socialization may still provide benefits for Black adolescents’ psychological adjustment.

“Mothers’ racial socialization may promote development of strong racial identity earlier in adolescence, setting the stage for the protective effects of youth racial identity that we observed in mid-adolescence,” Hochgraf said. “There is, however, mounting evidence that girls’ interactions and relationships with their fathers during adolescence have distinct implications for their weight concerns.”

Hochgraf said that in addition to having implications for creating new prevention programs, the findings also suggest new directions for research.

“The field may have overlooked sociocultural risk and protective factors of relevance to youth of color that may help explain why some of these youth develop weight concerns and others do not,” Hochgraf said. “It’s important to consider the distinct strengths and competencies of youth and families of color, and study how these may shape youths’ psychological development and adjustment.”

Susan McHale, distinguished professor of human development and family studies and professor of demography at Penn State, was a co-author of this study.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute on Drug Abuse helped support this research.

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Flavonoids may reduce mortality risk for people with Parkinson’s Disease

People with Parkinson’s Disease who eat more flavonoids — compounds found in richly colored foods like berries, cocoa and red wine — may have a lower mortality risk than those who don’t, according to a new study.

Specifically, the researchers found that when people who had already been diagnosed with Parkinson’s Disease (PD) ate more flavonoids, they had a lower chance of dying during the 34-year study period than those who did not consume as many flavonoids.

Additionally, they found that eating more flavonoids before being diagnosed with PD was associated with a lower risk of dying in men, but not in women.

“Adding a few servings of flavonoid-rich foods to their diets a week could potentially be an easy way for people with PD to help improve their life expectancy,” said Xinyuan Zhang, doctoral candidate in nutritional sciences at Penn State. “Greater consumption of berries and red wine, which are rich in the flavonoid anthocyanins, was particularly associated with lower mortality.”

Zhang noted that consumption of wine should not exceed the amount outlined in the Dietary Guidelines for Americans, which is one drink per day for women and two for men.

The study was published today (Jan. 26) in the journal Neurology.

According to the Parkinson’s Foundation, more than 60,000 people are diagnosed with PD each year, and more than 10 million people worldwide are living with the disease. The disease is caused by the brain not making enough dopamine and leads to tremors, stiffness and problems with balance.

Xiang Gao, professor of nutritional sciences at Penn State, said that while PD is not considered a fatal disease, its complications can lead to an increased risk of death, and that few studies have examined how the diet of people with PD can affect disease prognosis.

“Our group’s previous research found that when people without Parkinson’s ate more flavonoids, it was associated with a lower risk of them developing the disease in the future,” Gao said. “We wanted to further explore whether flavonoid intake could be linked to better survival in individuals who had already been diagnosed with Parkinson’s.”

For this study, the researchers analyzed data on 599 women and 652 men who had recently been diagnosed with PD. Participants were asked how often they ate certain flavonoid-rich foods, such as tea, apples, berries, oranges and orange juice, and red wine. Flavonoid intake was then calculated by multiplying the flavonoid content of those foods by how frequently they were consumed.

After controlling for factors like age and several dietary factors like total calories consumed and overall diet quality, the researchers found that the participants in the group of the highest 25% of flavonoid consumers had a 70% greater chance of survival than the lowest group.

The people in the highest group consumed about 673 milligrams (mg) of flavonoids each day while those in the lowest group consumed about 134 mg.

The researchers also analyzed the effects of individual flavonoids. They found that those in the top 25 percent consumers of anthocyanins — found in red wine and berries — had a 66% greater survival rate compared to those in the lowest 25%. Additionally, the top 25% consumers of flavan-3-ols — found in apples, tea and wine — had a 69% greater survival rate compared to the lowest 25%.

Zhang said that while the study did not examine the underlying mechanisms that may cause this association, the research team has proposed some theories.

“Flavonoids are antioxidants, so it’s possible they could be lowering chronic neuroinflammation levels,” Zhang said. “It’s also possible they may interact with enzyme activities and slow neuron loss and could protect against cognitive decline and depression, which are both associated with higher mortality risk.”

The researchers said future studies could help find the exact mechanisms behind flavonoid consumption and mortality risk in people with PD.

Samantha Molsberry, Harvard T.H. Chan School of Public Health; Tian-Shin Yeh, Harvard T.H. Chan School of Public Health; Aedin Cassidy, Queen’s University Belfast; Michael A. Schwarzschild, Massachusetts General Hospital; and Alberto Ascherio, Harvard T.H. Chan School of Public Health, also participated in this work.

The National Institute of Neurological Disorders and Stroke helped support this research.

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Flowered Steering: How Well Do Drivers Fare After Smoking Cannabis?

The steady rise in the use of cannabis — 18 states have legalized recreational use, 13 have decriminalized its use and 36 have medical cannabis laws — has provoked myriad questions and concerns about public health implications, including how cannabis may affect the abilities, real and perceived, of drivers under the influence.

In a novel, two-year randomized trial, conducted at the Center for Medicinal Cannabis Research (CMCR) at University of California San Diego School of Medicine, researchers recruited 191 regular cannabis users to partake of cannabis containing different levels of delta-9-tetrahydrocannabinol (THC), the psychoactive compound in cannabis or a placebo immediately before a series of driving simulation tests over several hours.

The findings are published in the January 26, 2022 online issue of JAMA Psychiatry.

Compared to participants who took the placebo, the THC group (who had smoked a cannabis cigarette with either 5.9 percent or 13.4 percent THC as they would “do at home to get high”) displayed significantly diminished ability on a Composite Drive Score (CDS) that assessed key simulated driving variables, such as swerving in lane, responding to divided attention tasks and following a lead car. However, not all individuals displayed significantly diminished driving skills compared to the placebo group; researchers said approximately 50 percent could be described as “impaired.”

The comparative decline was sharpest at the 30-minute and 1 hour-30 minute marks after inhaling cannabis, then leveled to borderline differences with the placebo at three hours-30 minute mark with no differences at 4 hours-30 minutes.

Importantly, said the study authors, driving scores did not differ based on THC content of the cigarette, both the 5.9 percent and 13.4 percent groups performed similarly, suggesting that users “self-titrated” by smoking in such a way to achieve similar highness levels.

Also, the group with the highest use-intensity cannabis in the past six months attained significantly higher blood THC concentrations after smoking, but performed no worse than those with lower THC concentrations, indicating behavioral tolerance.

However, they appeared to compensate by ingesting more THC and thus performed no better than less frequent users.

First and senior author Thomas Marcotte, PhD, co-director of CMCR and a professor of psychiatry at UC San Diego School of Medicine, noted that, “although users in the THC group felt impaired and were hesitant to drive at 30 minutes, by 1 hour-30 minutes they believed the impairment was wearing off and were more willing to drive.

“This was despite their performance not significantly improving from the 30 minute point. This may indicate a false sense of safety, and these first few hours may constitute a period of greatest risk since users are self-evaluating whether it is safe to drive.”

The study found no relationship between post-smoking blood THC concentrations and simulator performance. Co-author Robert Fitzgerald, PhD, professor of clinical pathology at UC San Diego School of Medicine and director of the Toxicology Laboratory and associate director of Clinical Chemistry Laboratory at UC San Diego Health said, “the complete lack of correlation between blood concentrations and driving performance was somewhat surprising. It’s strong evidence against developing ‘per se’ driving under the influence statutes.”

“Per se” laws, Latin for “by itself,” establish a statutory violation if a legal standard is breached, such as blood-alcohol concentration in driving under the influence laws.

The findings, said the authors, indicate that cannabis use resulted in diminished driving ability (in simulators), but when experienced marijuana users controlled their intake, impairment could not be inferred based on THC content of the cigarette, behavioral tolerance or THC blood concentrations.

“Our study of a large group of regular users underscores the complexity in understanding the relationship between cannabis intake and driving decrements, reinforces the challenges in communicating the varying level of risks associated with use and the difficulty in identifying the subset of individuals most at risk for impaired driving,” said Marcotte.

“This groundbreaking research indicates that cannabis use does impair driving ability, but factors differ from alcohol,” said California State Assembly member Tom Lackey (R-Palmdale). “For example, these data show that per se laws for THC levels are not supported scientifically. It also underscores the need for further research on this topic. Policymakers still need a better understanding of the effects of different ways of consuming higher concentration products to charter a path forward.”

The authors wrote that future research should address factors such as individual biologic differences, personal experience with cannabis and cannabis administration methods in relation to driving impairment.

“In studying medicinal cannabis, we need to be attentive to the fact that all medicines have risks as well as benefits,” said co-author Igor Grant, MD, CMCR director and Distinguished Professor of Psychiatry at UC San Diego School of Medicine. “Here, Dr. Marcotte and colleagues demonstrate that at least some drivers have reduced ability for several hours after intake. As we move forward, we need to learn more precisely who does and does not constitute a driving risk, and appropriately label cannabinoid medicines.”

Co-authors include: Anya Umlauf, David J. Grelotti, Emily G. Sones, all at UC San Diego; Philip M. Sobolesky, UC San Diego and Santa Clara Valley Medical Center; Breland E. Smith, UC San Diego and LetsGetChecked Labs, Monrovia, CA; Melissa A. Hoffman, UC San Diego and Vividion Therapeutics, San Diego; Jacqueline A. Hubbard, UC San Diego and Dartmouth-Hitchcock Medical Center; Joan Severson, Brainbaseline, Iowa City, IA; and Marilyn A. Huestis, Thomas Jefferson University, Philadelphia.

Funding for this research came, in part, from the State of California via Assembly Bill 266, Agreement #907.

Disclosures: Marcotte, Umlauf, Grelotti, Hoffman and Fitzgerald all report grants from the State of California during the conduct of this study.

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