Publisher Health

For cancer cells to metastasize, they must first break free of a tumor’s own defenses. Most tumors are sheathed in a protective “basement” membrane — a thin, pliable film that holds cancer cells in place as they grow and divide. Before spreading to other parts of the body, the cells must breach the basement membrane, a material that itself has been tricky for scientists to characterize.
Now MIT engineers have probed the basement membrane of breast cancer tumors and found that the seemingly delicate coating is as tough as plastic wrap, yet surprisingly elastic like a party balloon, able to inflate to twice its original size.
But while a balloon becomes much easier to blow up after some initial effort, the team found that a basement membrane becomes stiffer as it expands.
This stiff yet elastic quality may help basement membranes control how tumors grow. The fact that the membranes appear to stiffen as they expand suggests that they may restrain a tumor’s growth and potential to spread, or metastasize, at least to a certain extent.
The findings, published this week in the Proceedings of the National Academy of Sciences, may open a new route toward preventing tumor metastasis, which is the most common cause of cancer-related deaths.
“Now we can think of ways to add new materials or drugs to further enhance this stiffening effect, and increase the toughness of the membrane to prevent cancer cells from breaking through,” says Ming Guo, a lead author of the study and associate professor of mechanical engineering at MIT.

advertisement

Guo’s co-authors include first author Hui Li of Beijing Normal University, Yue Zheng and Shengqiang Cai of the University of California at Santa Diego, and MIT postdoc Yu Long Han.
Blowing up
The basement membrane envelopes not only cancerous growths but also healthy tissues and organs. The film — a fraction of the thickness of a human hair — serves as a physical support that holds tissues and organs in place and helps to shape their geometry, while also keeping them separate and distinct.
Guo’s group specializes in the study of cell mechanics, with a focus on the behavior of cancer cells and the processes that drive tumors to metastasize. The researchers had been investigating how these cells interact with their surroundings as they migrate through the body.
“A critical question we realized hasn’t gotten enough attention is, what about the membrane surrounding tumors?” Guo says. “To get out, cells have to break this layer. What is this layer in terms of material properties? Is it something cells have to work really hard to break? That’s what motivated us to look into the basement membrane.”
To measure the membrane’s properties, scientists have employed atomic force microscopy (AFM), using a tiny mechanical probe to gently push on the membrane’s surface. The force required to deform the surface can give researchers an idea of a material’s resistance or elasticity. But, as the basement membrane is exceedingly thin and tricky to separate from underlying tissue, Guo says it’s difficult to know from AFM measurements what the resistance of the membrane is, apart from the tissue underneath.

advertisement

Instead, the team used a simple technique, similar to blowing up a balloon, to isolate the membrane and measure its elasticity. They first cultured human breast cancer cells, which naturally secrete proteins to form a membrane around groups of cells known as tumor spheroids. They grew several spheroids of various sizes and inserted a glass microneedle into each tumor. They injected the tumors with fluid at a controlled pressure, causing the membranes to detach from the cells and inflate like a balloon.
The researchers applied various constant pressures to inflate the membranes until they reached a steady state, or could expand no more, then turned the pressure off.
“It’s a very simple experiment that can tell you a few things,” Guo says. “One is, when you inject pressure to swell this balloon, it gets much bigger than its original size. And as soon as you release the pressure, it gradually shrinks back, which is a classical behavior of an elastic material, similar to a rubber balloon.”
Elastic snap
As they inflated each spheroid, the researchers observed that, while a basement membrane’s ability to inflate and deflate showed that it was generally elastic like a balloon, the more specific details of this behavior were surprisingly different.
To blow up a latex balloon typically requires a good amount of effort and pressure to start up. Once it gets going and starts to inflate a bit, the balloon suddenly becomes much easier to blow up.
“Typically, once the radius of a balloon increases by about 38 percent, you don’t need to blow any harder — just maintain pressure and the balloon will expand dramatically,” Guo says.
This phenomenon, known as snap-through instability, is seen in balloons made of materials that are linearly elastic, meaning their inherent elasticity, or stiffness, does not change as they deform or inflate.
But based on their measurements, the researchers found that the basement membrane instead became stiffer, or more resistant as it inflated, indicating that the material is nonlinearly elastic, and able to change its stiffness as it deforms.
“If snap-through instability were to occur, a tumor would become a disaster — it would just explode,” Guo says. “In this case, it doesn’t. That indicates to me that the basement membrane provides a control on growth.”
The team plans to measure the membrane’s properties at different stages of cancer development, as well as its behavior around healthy tissues and organs. They are also exploring ways to modify the membrane’s elasticity to see whether making it stiffer will prevent cancer cells from breaking through.
“We are actively following up on how to modify the mechanics of these membranes, and apply perturbations on breast cancer models, to see if we can delay their invasion or metastasis,” Guo says. “This is an analogy to making a stiffer balloon, which we plan to try.”
This research was supported, in part, by the Alfred Sloan Foundation and the National Cancer Institute.

Depending on the topic, people’s attitudes can change from moment to moment or last a lifetime. The factors that make one opinion long-lasting and another ephemeral, however, are not always clear.
Past studies have demonstrated that opinions based on hard facts and data can remain constant over time, but new research published in the journal Psychological Science reveals that attitudes based on feelings and emotions can also stand the test of time. This research has implications for both predicting whose attitudes are fixed versus fleeting and how to nudge people to form more long-lasting opinions.
“We have known that encouraging people to think carefully and rationally can produce attitudes that change less in the future,” said Matthew Rocklage, a researcher with the University of Massachusetts, Boston, and co-lead author on the paper. “Our research, however, shows that opinions based on people’s emotional reactions can be particularly long-lasting as well.”
As part of their study, the researchers asked more than 1,000 people to what extent they believed attitudes based on feelings or emotional reactions were more stable over time than those based on thinking and rational analysis. Only 15% expressed any belief that attitudes based on emotion would be more stable over time.
To test the role that emotion plays in forming long-lasting attitudes, the researchers conducted seven independent studies involving more than 20,000 participants in a variety of real-world situations.
The first survey, which was conducted the day after Christmas, measured feelings about recently received gifts. The timing of this survey allowed the researchers to measure real-world reactions to a relatively newly formed attitude.
The participants were given a list of adjectives to describe their attitudes toward their gifts. Adjectives like “worthwhile” were associated with a practical reaction to the gift, whereas words like “delightful” were more strongly associated with an emotional reaction.
One month later, the participants completed a follow-up survey to test the endurance of their opinions. The results showed that the stronger the initial positive emotional reaction, the more likely that opinion remained fixed one month later.
The researchers conducted similar tests using virtually the same procedure but involving other scenarios, such as how much the participants supported consumer brands over time and how favorable their online restaurant reviews were between visits.
In the final test, participants read one of two messages about a fictitious aquatic animal. One message contained encyclopedic facts about the animal (low-emotion condition). The other message was about a swimmer’s underwater interaction with the animal (high-emotion condition). The participants in the high-emotion condition showed significantly less change in their attitude across time.
“Emotionality is an unappreciated predictor of long-lasting attitudes,” said Andrew Luttrell, a researcher at Ball State University and the other lead author on the paper. “These findings are important for understanding why some opinions are so difficult to change as well as how to create opinions that stick.”

Story Source:
Materials provided by Association for Psychological Science. Note: Content may be edited for style and length.

Illegal use of anabolic steroids not only has dangerous side effects during use but also can harm of men’s testicular function years after they stop abusing steroids, according to a study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
Anabolic steroids are synthetic forms of testosterone, and their abuse is prevalent among athletes worldwide. Some people use these steroids without a prescription to improve athletic performance or get a more muscular look. Known side effects of these drugs in men include breast growth, hair loss, shrunken testicles and lower testosterone levels. Also called hypogonadism, low testosterone can cause decreased sex drive, poor erections and a low sperm count.
“It is still debated whether illicit use of anabolic steroids causes long-lasting testosterone deficiency,” said Jon J. Rasmussen, M.D., Ph.D., the study’s principal investigator and a scientist at Rigshospitalet in Copenhagen, Denmark.
Researchers at the hospital have identified a hormone made by Leydig cells — cells in the testicles that produce testosterone — as a promising biological marker of testicular function, Rasmussen said. Because blood levels of testosterone can vary greatly during the day and vary by body composition, Rasmussen and his co-workers are investigating a more stable marker than testosterone, called serum insulin-like factor 3 (INSL3).
For this study, supported by Anti Doping Denmark, the research team included 132 participants from another study: men who did recreational strength training. Their ages ranged from 18 to 50 and averaged 32. Three study groups consisted of 46 men currently using anabolic steroids, 42 former steroid users and 44 who had never used these steroids. On average, former users had reportedly not taken anabolic steroids for 32 months.
Among current steroid users, INSL3 was markedly suppressed compared with former users and never-users, Rasmussen said. Compared with never-users, the former steroid users had lower INSL3 concentrations: 0.39 versus 0.59 microgram micrograms per liter. Furthermore, the longer the duration that the men reportedly used steroids, the lower their INSL3 levels, the researchers found.
“Our results suggest a long-lasting impaired gonadal capacity in previous anabolic steroid users,” Rasmussen said.
Although the clinically relevant difference in INSL3 levels is not yet known, because INSL3 measurement is primarily for research, he said their findings indicate that prior steroid users may have an increased risk of hypogonadism later in life.
“The results,” Rasmussen said, “raise the question whether some previous anabolic steroid users should receive medical stimulation therapy to increase Leydig cell capacity in the testicles.”
This therapy would include drugs used to block estrogen production or its conversion to testosterone, such as aromatase inhibitors and selective estrogen receptor modulators, he noted.

Story Source:
Materials provided by The Endocrine Society. Note: Content may be edited for style and length.

Smart speakers, such as Amazon Echo and Google Home, have proven adept at monitoring certain health care issues at home. For example, researchers at the University of Washington have shown that these devices can detect cardiac arrests or monitor babies breathing.
But what about tracking something even smaller: the minute motion of individual heartbeats in a person sitting in front of a smart speaker?
UW researchers have developed a new skill for a smart speaker that for the first time monitors both regular and irregular heartbeats without physical contact. The system sends inaudible sounds from the speaker out into a room and, based on the way the sounds are reflected back to the speaker, it can identify and monitor individual heartbeats. Because the heartbeat is such a tiny motion on the chest surface, the team’s system uses machine learning to help the smart speaker locate signals from both regular and irregular heartbeats.
When the researchers tested this system on healthy participants and hospitalized cardiac patients, the smart speaker detected heartbeats that closely matched the beats detected by standard heartbeat monitors. The team published these findings March 9 in Communications Biology.
“Regular heartbeats are easy enough to detect even if the signal is small, because you can look for a periodic pattern in the data,” said co-senior author Shyam Gollakota, a UW associate professor in the Paul G. Allen School of Computer Science & Engineering. “But irregular heartbeats are really challenging because there is no such pattern. I wasn’t sure that it would be possible to detect them, so I was pleasantly surprised that our algorithms could identify irregular heartbeats during tests with cardiac patients.”
While many people are familiar with the concept of a heart rate, doctors are more interested in the assessment of heart rhythm. Heart rate is the average of heartbeats over time, whereas a heart rhythm describes the pattern of heartbeats.

advertisement

For example, if a person has a heart rate of 60 beats per minute, they could have a regular heart rhythm — one beat every second — or an irregular heart rhythm — beats are randomly scattered across that minute but they still average out to 60 beats per minute.
“Heart rhythm disorders are actually more common than some other well-known heart conditions. Cardiac arrhythmias can cause major morbidities such as strokes, but can be highly unpredictable in occurrence, and thus difficult to diagnose,” said co-senior author Dr. Arun Sridhar, assistant professor of cardiology at the UW School of Medicine. “Availability of a low-cost test that can be performed frequently and at the convenience of home can be a game-changer for certain patients in terms of early diagnosis and management.”
The key to assessing heart rhythm lies in identifying the individual heartbeats. For this system, the search for heartbeats begins when a person sits within 1 to 2 feet in front of the smart speaker. Then the system plays an inaudible continuous sound, which bounces off the person and then returns to the speaker. Based on how the returned sound has changed, the system can isolate movements on the person — including the rise and fall of their chest as they breathe.
“The motion from someone’s breathing is orders of magnitude larger on the chest wall than the motion from heartbeats, so that poses a pretty big challenge,” said lead author Anran Wang, a doctoral student in the Allen School. “And the breathing signal is not regular so it’s hard to simply filter it out. Using the fact that smart speakers have multiple microphones, we designed a new beam-forming algorithm to help the speakers find heartbeats.”
The team designed what’s called a self-supervised machine learning algorithm, which learns on the fly instead of from a training set. This algorithm combines signals from all of the smart speaker’s multiple microphones to identify the elusive heartbeat signal.

advertisement

“This is similar to how Alexa can always find my voice even if I’m playing a video or if there are multiple people talking in the room,” Gollakota said. “When I say, ‘Hey, Alexa,’ the microphones are working together to find me in the room and listen to what I say next. That’s basically what’s happening here but with the heartbeat.”
The heartbeat signals that the smart speaker detects don’t look like the typical peaks that are commonly associated with traditional heartbeat monitors. The researchers used a second algorithm to segment the signal into individual heartbeats so that the system could extract what is known as the inter-beat interval, or the amount of time between two heartbeats.
“With this method, we are not getting the electric signal of the heart contracting. Instead we’re seeing the vibrations on the skin when the heart beats,” Wang said.
The researchers tested a prototype smart speaker running this system on two groups: 26 healthy participants and 24 hospitalized patients with a diversity of cardiac conditions, including atrial fibrillation and heart failure. The team compared the smart speaker’s inter-beat interval with one from a standard heartbeat monitor. Of the nearly 12,300 heartbeats measured for the healthy participants, the smart speaker’s median inter-beat interval was within 28 milliseconds of the standard monitor. The smart speaker performed almost as well with cardiac patients: of the more than 5,600 heartbeats measured, the median inter-beat interval was within 30 milliseconds of the standard.
Currently this system is set up for spot checks: If a person is concerned about their heart rhythm, they can sit in front of a smart speaker to get a reading. But the research team hopes that future versions could continuously monitor heartbeats while people are asleep, something that could help doctors diagnose conditions such as sleep apnea.
“If you have a device like this, you can monitor a patient on an extended basis and define patterns that are individualized for the patient. For example, we can figure out when arrhythmias are happening for each specific patient and then develop corresponding care plans that are tailored for when the patients actually need them,” Sridhar said. “This is the future of cardiology. And the beauty of using these kinds of devices is that they are already in people’s homes.”
This research was funded by the National Science Foundation.

Head injury in the United States is common, with over 23 million adults age 40 or older reporting a history of head injury with loss of consciousness. Many head injuries can be caused by a host of different situations — from car and motorcycle accidents to sports injuries. What’s more, it has become increasingly recognized that the effects from head injuries are long-lasting. New research led by the Perelman School of Medicine at the University of Pennsylvania shows that a single head injury could lead to dementia later in life. This risk further increases as the number of head injuries sustained by an individual increases. The findings also suggest stronger associations of head injury with risk of dementia among women compared to among men and among white as compared to among Black populations.
The researchers, whose findings were published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, conducted the investigation using data from the Atherosclerosis Risk in Communities (ARIC) Study, which aimed to uncover associations between head injury and dementia over the span of 25 years in a diverse population in the United States. Previously, data on traumatic brain injury has been limited to select populations, such as military and medical claims databases. These are among the first findings to specifically investigate head injury and dementia risk in both Black and white populations, as well as among both males and females, in a community-based setting.
“Head injury is a significant risk factor for dementia, but it’s one that can be prevented. Our findings show that the number of head injuries matter — more head injuries are associated with greater risk for dementia,” said lead investigator, Andrea L.C. Schneider, MD, PhD, an assistant professor of Neurology at Penn. “The dose-dependence of this association suggests that prevention of head injury could mitigate some risk of dementia later in life. While head injury is not the only risk factor for dementia, it is one risk factor for dementia that is modifiable by behavior changes such as wearing helmets and seat belts.”
The findings show that compared to participants who never experienced a head injury, a history of a single prior head injury was associated with a 1.25 times increased risk of dementia, and a history of two or more prior head injuries was associated with over 2 times increased risk of dementia compared to individuals without a history of head injury. Overall, 9.5 percent of all dementia cases in the study population could be attributed to at least one prior head injury.
To illustrate the relationship between dementia and head injuries, the authors gathered data from a diverse cohort with a mean baseline age of 54 years, comprised of 56 percent female and 27 percent Black participants from four different communities across the United States. Participants were followed for a median of 25 years through up to six in-person visits and semi-annual telephone follow-ups. Data on head injuries of participants was drawn from hospital records, as well as self-reporting from some participants.
Previous research on dementia and traumatic brain injuries suggests that women are at higher risk for dementia compared to men. Additionally, Black populations overall are at higher risk for dementia compared to people who are white. However, few prior studies have evaluated for possible differences in associations of head injury with dementia risk by sex and race.
This data from the ARIC study found evidence that females were more likely to experience dementia as a result of head injury than males. Further, the study showed that although there is increased dementia risk associated with head injury among both White and Black participants, White participants were at higher risk for dementia after head injury compared to Black participants. The authors conclude that more research is needed to better understand reasons for these observed sex and race differences in the association of head injury with dementia risk.
“Given the strong association of head injury with dementia, there is an important need for future research focused on prevention and intervention strategies aimed at reducing dementia after head injury,” Schneider said. “The results of this study have already led to several ongoing research projects, including efforts to uncover the causes of head injury-related dementia as well as investigations into reasons underlying the observed sex and race differences in the risk of dementia associated with head injury.”

Story Source:
Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.

Modern hospitals and antibiotic treatment alone did not create all the antibiotic resistant strains of bacteria we see today. Instead, selection pressures from before widespread use of antibiotics influenced some of them to develop, new research has discovered.
By using analytical and sequencing technology that has only been developed in recent years, scientists from Wellcome Sanger Institute, University of Oslo and University of Cambridge have created an evolutionary timeline of the bacterium, Enterococcus faecalis, which is a common bacterium that can cause antibiotic resistant infections in hospitals.
The results, published today (9th March 2021) in Nature Communications show that this bacterium has the ability to adapt very quickly to selection pressures, such as the use of chemicals in farming as well as the development of new medications, which have caused different strains of the same bacterium to be found in many places worldwide, from the majority of people’s guts to many wild birds. As it is so widespread, the researchers suggest people should be screened for this type of bacteria when entering the hospital, in the same way they are for other superbugs, to help reduce the possibility of developing and spreading infection within healthcare.
Enterococcus faecalis is a common bacterium that, in most people, is found in the intestinal tract and doesn’t cause harm to the host. However, if someone is immunocompromised and this bacterium gets into the bloodstream, it can cause a serious infection.
In hospitals, it is more common to find antibiotic resistant strains of E. faecalis and it was initially thought that the wide use of antibiotics and other antibacterial control measures in modern hospitals caused these strains to develop.
In a new study, scientists from Wellcome Sanger Institute, University of Oslo and University of Cambridge analysed around 2000 samples of E. faecalis from 1936 to present day using blood stream isolates from patients and stool samples from animals and healthy humans.
By sequencing the genome (including chromosomes and plasmids) using technology from Oxford Nanopore, the team mapped the evolutionary journey of the bacterium and created a timeline of when and where different strains developed, including those nowadays found to be resistant to antibiotics. They found that antibiotic resistant strains developed earlier than previously thought, before the widespread use of antibiotics, and therefore it was not antibiotic use alone that caused these to emerge.
Researchers found that agricultural and early medical practices, such as the use of arsenic and mercury, influenced the evolution of some of the strains we see now. In addition to this, strains similar to the antibiotic resistant variants we see in hospitals now were found in wild birds. This shows how adaptable and flexible this species of bacterium is at evolving into new strains in the face of different adversity.
Professor Jukka Corander, co-lead author and Associate Faculty member at the Wellcome Sanger Institute, said: “This is the first time we have been able to map out the full evolution of E. faecalis from samples up to 85 years old, which enables us to see the detailed effect of human lifestyles, agriculture and medicines on the development of different bacterial strains. Having the full timeline of evolutionary changes would not have been possible without analytical and sequencing techniques that can be found at the Sanger Institute.”
Dr Anna Pöntinen, co-lead author and post-doctoral fellow at University of Oslo, said: “Currently, when patients are admitted to hospital, they are swabbed for some antibiotic resistant bacteria and fungi and are isolated to ensure that infection rates are kept as low as possible. Thanks to this study, it is possible to scrutinize the diversity of E. faecalis and identify those that are more prone to spread within hospitals and thus could cause harm in immunocompromised people. We believe that it could be beneficial to also screen for E. faecalis on admission to hospitals.”
Professor Julian Parkhill, co-author and Professor in the Department of Veterinary Medicine at University of Cambridge, said: “This research has discovered that these hospital-associated strains of antibiotic resistant bacteria are much older than we previously thought, and has highlighted their incredible metabolic flexibility combined with numerous mechanisms enhancing their survival under harsh conditions that has allowed them to spread widely across the globe.”