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A breakthrough in the physics of blood clotting

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New Research shows platelets do their job better when not in total sync with one another

Heart attacks and strokes — the leading causes of death in human beings — are fundamentally blood clots of the heart and brain. Better understanding how the blood-clotting process works and how to accelerate or slow down clotting, depending on the medical need, could save lives.

New research by the Georgia Institute of Technology and Emory University published in the journal Biomaterials sheds new light on the mechanics and physics of blood clotting through modeling the dynamics at play during a still poorly understood phase of blood clotting called clot contraction.

“Blood clotting is actually a physics-based phenomenon that must occur to stem bleeding after an injury,” said Wilbur A. Lam, W. Paul Bowers Research Chair in the Department of Pediatrics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. “The biology is known. The biochemistry is known. But how this ultimately translates into physics is an untapped area.”

And that’s a problem, argues Lam and his research colleagues, since blood clotting is ultimately about “how good of a seal can the body make on this damaged blood vessel to stop bleeding, or when this goes wrong, how does the body accidentally make clots in our heart vessels or in our brain?”

How Blood Clotting Works

The workhorses to stem bleeding are platelets — tiny 2-micrometer cells in the blood in charge of making the initial plug. The clot that forms is called fibrin, which acts as a glue scaffold that the platelets attach to and pull against. Blood clot contraction arises when these platelets interact with the fibrin scaffold. To demonstrate the contraction, researchers embedded a 3-millimeter Jell-O mold of a LEGO figure with millions of platelets and fibrin to recreate a simplified version of a blood clot.

“What we don’t know is, ‘How does that work?’ ‘What’s the timing of it so all these cells work together — do they all pull at the same time?’ Those are the fundamental questions that we worked together to answer,” Lam said.

Lam’s lab collaborated with Georgia Tech’s Complex Fluids Modeling and Simulation group headed by Alexander Alexeev, professor and Anderer Faculty Fellow in the George W. Woodruff School of Mechanical Engineering, to create a computational model of a contracting clot. The model incorporates fibrin fibers forming a three-dimensional network and distributed platelets that can extend filopodia, or the tentacle-like structures that extend from cells so they can attach to specific surfaces, to pull the nearby fibers.

Model Shows Platelets Dramatically Reducing Clot Volume

When the researchers simulated a clot where a large group of platelets was activated at the same time, the tiny cells could only reach nearby fibrins because the platelets can extend filopodia that are rather short, less than 6 micrometers. “But in a trauma, some platelets contract first. They shrink the clot so the other platelets will see more fibrins nearby, and it effectively increases the clot force,” Alexeev explained. Due to the asynchronous platelet activity, the force enhancement can be as high as 70%, leading to a 90% decrease of the clot volume.

“The simulations showed that the platelets work best when they’re not in total sync with each other,” Lam said. “These platelets are actually pulling at different times and by doing that they’re increasing the efficiency (of the clot).”

This phenomenon, dubbed by the team asynchronous mechanical amplification, is most pronounced “when we have the right concentration of the platelets corresponding to that of healthy patients,” Alexeev said.

Research Could Lead to Better Ways to Treat Clotting, Bleeding Issues

The findings could open medical options for people with clotting issues, said Lam, who treats young patients with blood disorders as a pediatric hematologist in the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

“If we know why this happens, then we have a whole new potential avenue of treatments for diseases of blood clotting,” he said, emphasizing that heart attacks and strokes occur when this biophysical process goes wrong.

Lam explained that fine tuning the contraction process to make it faster or more robust could help patients who are bleeding from a car accident or, in the case of a heart attack, make the clotting less intense and slow it down.

“Understanding the physics of this clot contraction could potentially lead to new ways to treat bleeding problems and clotting problems.”

Alexeev added that their research also could lead to new biomaterials such as a new type of Band-Aid that could help augment the clotting process.

First author and Georgia Tech Ph.D. candidate Yueyi Sun noted the simplicity of the model and the fact that the simulations allowed the team to understand how the platelets work together to contract the fibrin clot as they would in the body.

“When we started to include the heterogeneous activation, suddenly it gave us the correct volume contraction,” she said. “Allowing the platelets to have some time delay so one can use what the previous ones did as a better starting point was really neat to see. I think our model can potentially be used to provide guidelines for designing novel active biological and synthetic materials.”

Sun agreed with her research colleagues that this phenomenon might occur in other aspects of nature. For example, multiple asynchronous actuators can fold a large net more effectively to enhance packaging efficiency without the need of incorporating additional actuators.

“It theoretically could be an engineered principle,” Lam said. “For a wound to shrink more, maybe we don’t have the chemical reactions occur at the same time — maybe we have different chemical reactions occur at different times. You gain better efficiency and contraction when one allows half or all of the platelets to do the work together.”

Building on the research, Sun hopes to examine more closely how a single platelet force converts or is transmitted to the clot force, and how much force is needed to hold two sides of a graph together from a thickness and width standpoint. Sun also intends to include red blood cells in their model since they account for 40% of all blood and play a role in defining the clot size.

“If your red blood cells are too easily trapped in your clot, then you are more likely to have a large clot, which causes a thrombosis issue,” she explained.

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CITATION: Y. Sun, et.al., “Platelet heterogeneity enhances blood clot volumetric contraction: An example of asynchrono-mechanical amplification.” (Biomaterials 274, 120828, 2021) https://doi.org/10.1016/j.biomaterials.2021.120828

The Georgia Institute of Technology, or Georgia Tech, is a top 10 public research university developing leaders who advance technology and improve the human condition.

The Institute offers business, computing, design, engineering, liberal arts, and sciences degrees. Its nearly 40,000 students, representing 50 states and 149 countries, study at the main campus in Atlanta, at campuses in France and China, and through distance and online learning.

As a leading technological university, Georgia Tech is an engine of economic development for Georgia, the Southeast, and the nation, conducting more than $1 billion in research annually for government, industry, and society.

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Source: https://bioengineer.org/a-breakthrough-in-the-physics-of-blood-clotting/

Bioengineer

No health worries for children born to mothers given seasonal flu vaccine in pregnancy

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uOttawa/CHEO study finds no increased risk of early childhood health issues following exposure to seasonal flu vaccination during pregnancy

A population-based study, published today in JAMA, has found flu vaccination during pregnancy does not lead to an increased risk of adverse early childhood health outcomes.

Although pregnant people are not more susceptible to acquiring influenza infection, they are at an increased risk of severe illness and complications if they get the flu during pregnancy. For this reason, all pregnant people are advised to receive a flu shot each year, yet only 36 percent received it according to a study monitoring four flu seasons in Nova Scotia. Safety concerns are reportedly a leading reason people may not receive influenza vaccination in pregnancy.

Dr. Deshayne Fell, an Associate Professor of Epidemiology in the Faculty of Medicine at uOttawa and a Scientist at the CHEO Research Institute, a pediatric healthcare and research centre, led the study along with researchers in Ontario and at Dalhousie University in Nova Scotia. The study followed over 28,000 children from birth up to an average age of 3 ½ years, with the results suggesting that maternal influenza vaccination during pregnancy was not associated with:

– Immune-related health conditions, such as asthma, ear infections or other types of infection.

– Non-immune-related health problems like neoplasms, sensory impairment.

– Nonspecific health needs such as Emergency Department visits and hospitalizations did not increase.

“This study adds to what we know from other recent studies showing no harmful effects of flu vaccination during pregnancy on the longer-term health of children,” says Dr. Fell, whose other recent work includes studying the effectiveness and safety of COVID-19 vaccines during pregnancy. “This is important because we know that getting the flu shot during pregnancy not only protects the pregnant person, but has the added bonus of protecting newborn babies from getting the flu during their first few months of life, which is when they are most susceptible to respiratory infections but still too young to get the flu shot themselves.”

The study, Association of Maternal Influenza Vaccination During Pregnancy with Early Childhood Health Outcomes, is published in JAMA.

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About the University of Ottawa
The University of Ottawa is home to over 50,000 students, faculty and staff, who live, work and study in both French and English. Our campus is a crossroads of cultures and ideas, where bold minds come together to inspire game-changing ideas. We are one of Canada’s top 10 research universities–our professors and researchers explore new approaches to today’s challenges. One of a handful of Canadian universities ranked among the top 200 in the world, we attract exceptional thinkers and welcome diverse perspectives from across the globe. http://www.uottawa.ca

About CHEO
Dedicated to the best life for every child and youth, CHEO is a global leader in pediatric health care and research. Based in Ottawa, CHEO includes a hospital, children’s treatment centre, school and research institute, with satellite services located throughout Eastern Ontario. CHEO provides excellence in complex pediatric care, research and education. We are committed to partnering with families and the community to provide exceptional care — where, when and how it’s needed. CHEO is a partner of the Kids Come First Health Team, a network of partners working to create a high quality, standardized and coordinated system for pediatric health care that is centred around children, youth and their families. Every year, CHEO helps more than 500,000 children and youth from Eastern Ontario, western Quebec, Nunavut and Northern Ontario. http://www.cheo.on.ca

https://media.uottawa.ca/news/study-no-health-worries-children-born-mothers-who-received-seasonal-flu-vaccine-during

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Bioengineer

How your phone can predict depression and lead to personalized treatment

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Study used data from cell phone apps and watches, brain activity and lifestyle factors to generate predictions of depression; results could lead to individualized treatment plans for mental health

According to the National Alliance on Mental Illness and the World Health Organization, depression affects 16 million Americans and 322 million people worldwide. Emerging evidence suggests that the COVID-19 pandemic is further exacerbating the prevalence of depression in the general population. With this trajectory, it is evident that more effective strategies are needed for therapeutics that address this critical public health issue.

In a recent study, publishing in the June 9, 2021 online edition of Nature Translational Psychiatry, researchers at University of California San Diego School of Medicine used a combination of modalities, such as measuring brain function, cognition and lifestyle factors, to generate individualized predictions of depression.

The machine learning and personalized approach took into account several factors related to an individual’s subjective symptoms, such as sleep, exercise, diet, stress, cognitive performance and brain activity.

“There are different underlying reasons and causes for depression,” said Jyoti Mishra, PhD, senior author of the study, director of NEATLabs and assistant professor in the Department of Psychiatry at UC San Diego School of Medicine. “Simply put, current health care standards are mostly just asking people how they feel and then writing a prescription for medication. Those first-line treatments have been shown to be only mild to moderately effective in large trials.

“Depression is a multifaceted illness, and we need to approach it with personalized treatment whether that be therapy with a mental health professional, more exercise or a combination of approaches.”

The one-month study collected data from 14 participants with depression using smartphone applications and wearables (like smart watches) to measure mood and lifestyle variables of sleep, exercise, diet and stress, and paired these with cognitive evaluations and electroencephalography, using electrodes on the scalp to record brain activity.

The goal was not to make any comparisons across individuals, but to model the predictors of each person’s daily fluctuations in depressed mood.

The researchers developed a new machine-learning pipeline to systematically identify distinct predictors of low mood in each individual.

As an example, exercise and daily caffeine intake emerged as strong predictors of mood for one participant, but for another, it was sleep and stress that were more predictive, while in a third subject, the top predictors were brain function and cognitive responses to rewards.

“We should not be approaching mental health as one size fits all. Patients will benefit by having more direct and quantified insight onto how specific behaviors may be feeding their depression. Clinicians can leverage this data to understand how their patients might be feeling and better integrate medical and behavioral approaches for improving and sustaining mental health,” said Mishra.

“Our study shows that we can use the technology and tools that are readily available, like cell phone apps, to collect information from individuals with or at risk for depression, without significant burden to them, and then harness that information to design personalized treatment plans.”

Mishra said next steps include examining if the personalized treatment plans guided by the data and machine learning are effective.

“Our findings could have broader implications than depression. Anyone seeking greater well-being could benefit from insights quantified from their own data. If I don’t know what is wrong, how do I know how to feel better?”

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Co-authors include: Rutvik Shah, Gillian Grennan, MariamZafar-Khan, Fahad Alim, Sujit Dey, all with UC San Diego; and Dhakshin Ramanathan with UC San Diego and the VA San Diego Medical Center.

Disclosure: Shah, Dey and Mishra have an Invention Disclosure filed for “Personalized Machine Learning of Depressed Mood using Wearables.”

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Source: https://bioengineer.org/how-your-phone-can-predict-depression-and-lead-to-personalized-treatment/

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The buck stops where? UNH research records longest-ever deer distance

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DURHAM, N.H.–Why did the deer cross the road? According to research from the University of New Hampshire to keep going and going and going. Researchers have discovered the longest distance ever recorded by an adult male white-tailed deer–300 kilometers, or close to 200 miles, in just over three weeks. The finding has important implications for population management and the transmission of disease, especially chronic wasting disease, a fatal neurological disease.

“Deer are one of the most abundant, well-known and intensely managed species of wildlife in the United States,” said Remington Moll, assistant professor of wildlife ecology and lead author. “So, to make this discovery despite the fact that they are so well studied is pretty surprising.”

In their study, published in the journal Ecology and Evolution, researchers analyzed data from GPS radio collars on more than 600 deer in Missouri. One dispersal, or long-distance journey, of an adult white-tailed deer stood out for its length, duration and age of the deer. The buck travelled close to 300 kilometers over 22 days by moving an average of 13.6 kilometers per day (almost eight and a half miles), crossing a major river seven times, an interstate highway, a railroad and eight state highways. To confirm the findings, the researchers surveyed the scientific literature for other dispersals of white-tailed deer. The deer, known as N17003, stood head and antlers above others; his walkabout was 174 kilometers longer than any other recorded for an adult male deer.

“This extraordinary movement just jumped out from the others we tracked,” said Moll. “At first, we thought it was an error. It looks like someone took the GPS collar and drove across the state of Missouri.”

The findings were remarkable not only for the deer’s range–he roamed a distance equal to that between New York City and Baltimore–but also because unlike juvenile males, who move to seek breeding opportunities, adult males tend to stay put. Movements were faster and more directional than those in their home territory and were faster and more directional at night than during the day when the deer frequently sheltered in forest cover. The journey, which happened in November 2017, occurred during hunting season.

“We call this a rare event, but we haven’t been putting collars out for that long, and not in these large numbers,” said Moll. “It’s entirely possible that it could be happening with greater frequency than we’ve known.”

Nearly eight million Americans hunt deer which contributes more than $20 billion to the U.S. economy. The researchers say that understanding the distance deer travel and how they do it is important for managing the species and controlling chronic wasting disease, a fatal neurological disease spread by direct contact and the environment. Knowing that deer are crossing county or even state lines highlights a need for regional management coordination.

Funding for this study was provided by the Missouri Department of Conservation, the U.S. Fish and Wildlife Service and the University of Montana.

Co-authors are Jon Roberts and Joshua Millspaugh, University of Montana; Kevyn Wiskirchen, Jason Sumners, Jason Isabelle and Barbara Keller, Missouri Department of Conservation; and Robert Montgomery, Michigan State University.

The >University of New Hampshire inspires innovation and transforms lives in our state, nation, and world. More than 16,000 students from all 50 states and 71 countries engage with an award-winning faculty in top-ranked programs in business, engineering, law, health and human services, liberal arts and the sciences across more than 200 programs of study. As one of the nation’s highest-performing research universities, UNH partners with NASA, NOAA, NSF and NIH, and receives more than $110 million in competitive external funding every year to further explore and define the frontiers of land, sea and space.

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PHOTOS FOR DOWNLOAD

Image: http://unh.edu/sites/default/files/deer_distance_monroebuck_.jpg

Credit: Missouri Department of Conservation

Caption: Fleeting glimpse of an adult white-tailed deer, known as N17003, that traveled the longest distance ever recorded by a UNH researcher – over 200 miles in 22 days.

Image: http://unh.edu/sites/default/files/deer_map_300kdeerdispersal_.jpg

Credit: UNH

Caption: Map chronicling the multi-county journey of an adult white-tailed deer, known as N17003, traveling the longest distance ever recorded – over 300 kilometers in just over three weeks.

https://www.unh.edu/unhtoday/news/release/2021/06/08/buck-stops-where-unh-research-records-longest-ever-deer-distance

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Serenading Lusitanian toadfish drowned out by water traffic

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During spring, Lusitanian toadfish (Halobatrachus didactylus) suitors form choirs in Portugal’s Tagus estuary to serenade the females, vibrating their swim bladders to produce a call, known as a boatwhistle, which sounds like a vibrating cell phone. The males also listen in on each other to check whether anyone is intruding on their territory. But sadly, their performances are no longer conducted in hushed reverence. Revving motorboats and churning ferry propellors and engines fill the water with unwelcome noise, which made Clara Amorim, Daniel Alves, Manuel Vieira and Paulo Fonseca, from the Universidade de Lisboa, Portugal, wonder whether human noise pollution is playing havoc with the garrulous fish’s ability to communicate. They publish their discovery that toadfish serenades are being drowned out by water traffic that also disrupts their ability to croon together in Journal of Experimental Biology at https://journals.biologists.com/jeb.

‘We had previously measured how far toadfishes could communicate with each other’, says Alves, who worked with local fisherman to collect the vocal fish. Once the fish were comfortable in the lab, Alves and Fonseca tested their hearing by playing boatwhistles – which had been recorded at distances from 0.1-15 m – while logging the fishes’ brainwaves as they listened to the sound against a silent background. Then, the duo added the whine of an outboard motor or a rumbling ferryboat and rechecked the brainwaves, to find out whether the fish were still able to hear the serenades.

Unfortunately, the outboard motor almost completely drowned out the recordings of the males. One boatwhistle that had been clear up to 10.4 m away in absolute silence became inaudible over distances of more than 2.5 m and the range of another toadfish rumble fell to just 2.0 m. However, the ferryboat seemed to have less of an impact on the toadfishes’ hearing, cutting the range over which one boatwhistle could be heard by 4 m, to 6.3 m, while the other, which had been so badly affected by the outboard motor, could be heard over slightly longer distances (6.7 m). Water traffic is clearly affecting the ability of these vocal fish to hear one another, but does the sound of passing vessels affect how harmonising toadfish croon together?

To find out, Vieira, Amorim and Fonseca crossed the Tagus to a quiet toadfish breeding ground, providing the serenading residents with 12 custom-built concrete nests, each equipped with an underwater microphone to record their boatwhistles as they settled into duetting with nearby males to attract females. In peaceful waters, the neighbours coordinated well, slightly advancing or delaying their responses to each other’s calls depending on their proximity. However, when the scientists played recordings of passing ferries and motorboats to the courting males, the toadfishes’ coordination broke down entirely, with serenading duetters interjecting more randomly between their neighbour’s timed rumbles.

‘These results demonstrate that boat noise can severely reduce the distance at which the Lusitanian toadfish can communicate and affect how they produce sounds in their choruses’, says Vieira, who warns that noisy human water traffic could dramatically affect the Lusitanian toadfish’s love life.

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Source: https://bioengineer.org/serenading-lusitanian-toadfish-drowned-out-by-water-traffic/

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