Researchers have developed a new ultrasound method that for the first time can measure the level of tension in human tissue – a key indicator of disease. The breakthrough, published in the journal Science Advances, could be used to build new ultrasound machines that are able to better discriminate between abnormal tissue, scarring, and cancer.
Images produced by the current techniques ultrasound used in healthcare aren’t usually enough to diagnose whether tissues are abnormal. To improve diagnosis, the researchers developed a way to measure forces such as tension by using an ultrasound machine. Tension is generated in all living tissue, so measuring it can indicate whether tissue is functioning properly or if it’s affected by disease.
The researchers harnessed a technique from a rail project at the University of Sheffield, which uses sound waves to measure tension along railway lines. The technique, used both for rail and medical ultrasound, relies on a simple principle: the greater the tension, the faster sound waves propagate. Using this principle, the researchers developed a method that sends two sound waves in different directions. The tension is then related to the speed of the waves by using mathematical theories developed by the researchers.
Previous ultrasound methods have struggled to show the difference between stiff tissue or tissue under tension. The developed technique is the first capable of measuring tension for any type of soft tissue, and without knowing anything about it. In this new paper, the researchers describe the new method and demonstrate how they used it to measure tension inside a muscle.
Study leader Dr Artur Gower, Lecturer in Dynamics at the University of Sheffield, said: “When you go to the hospital, a doctor might use an ultrasound device to create an image of an organ, such as your liver, or another part of your body, such as the gut, to help them explore what the cause of a problem might be. One of the limitations of ultrasounds used in healthcare now is that the image alone is not enough to diagnose whether any of your tissues are abnormal.
“What we’ve done in our research is develop a new way of using ultrasound to measure the level of tension in tissue. This level of detail can tell us whether tissues are abnormal or if they are affected by scarring or disease. This technique is the first time that ultrasound can be used to measure forces inside tissue, and it could now be used to build new ultrasound machines capable of diagnosing abnormal tissue and disease earlier.”
A new biosensor engineered by Penn State researchers offers scientists the first dynamic glimpses of the elusive – and vital – manganese ion. The researchers engineered the sensor from a natural protein called lanmodulin, which binds rare earth elements with high selectivity and was discovered five years ago by some of this study’s researchers. Their findings are published in the Proceedings of the National Academy of Sciences.
The researchers genetically reprogrammed the protein to favour manganese over other common transition metals like iron and copper, unlike most transition metal-binding molecules. The sensor could have broad applications in biotechnology to advance understanding of photosynthesis, host-pathogen interactions and neurobiology.
Like iron, copper and zinc, manganese is an essential metal for plants and animals. Its function is to activate enzymes. In humans, manganese is linked to neural development. Accumulation of excess manganese in the brain induces Parkinsonian-like motor disease, whereas reduced manganese levels have been observed in association with Huntington’s disease, the researchers explained.
“We believe that this is the first sensor that is selective enough for manganese for detailed studies of this metal in biological systems,” said Jennifer Park, a graduate student at Penn State and lead author on the paper. “We’ve used it – and seen the dynamics of how manganese comes and goes in a living system, which hasn’t been possible before.”
She explained that the team was able to monitor the behaviour of manganese within bacteria and are now working to engineer even tighter binding sensors to potentially study how the metal works in mammalian systems.
Scientific understanding of manganese has lagged behind that of other essential metals, in part because of a lack of techniques to visualise its concentration, localisation and movement within cells. The new sensor opens the door for all kinds of new research, explained Joseph Cotruvo, associate professor of chemistry at Penn State and senior author on the paper.
“There are so many potential applications for this sensor,” said Cotruvo. “Personally, I am particularly interested in seeing how manganese interacts with pathogens.”
He explained that the body works hard to restrict the iron that most bacterial pathogens need for survival, and so those pathogens instead turn to manganese.
“We know there is this tug-of-war for vital metals between the immune system and these invading pathogens, but we haven’t been able to fully understand these dynamics, because we couldn’t see them in real time,” he said, adding that with new capabilities to visualise the process, researchers have tools to potentially develop new drug targets for a range of infections for which resistance has emerged to common antibiotics, like staph (MRSA).
Designing proteins to bind to particular metals is an intrinsically difficult problem, Cotruvo explained, because there are so many similarities between the transition metals present in cells. As a result, there has been a lack of chemical biology tools with which to study manganese physiology in live cells.
“The question for us was, can we engineer a protein to only bind to one thing, a manganese ion, even in the presence of a huge excess of other very similar-looking things, like calcium, magnesium, iron, and zinc ions?” Cotruvo said. “What we had to do was create a binding site arranged in just the right way, so that this protein bond was more stable in manganese than any other metal.”
Having successfully demonstrated lanmodulin is capable of such a task, the team is now planning to use it as a scaffold from which to evolve other types of biological tools for sensing and recovering many different metal ions that have biological and technological importance.
“If you can figure out ways of discriminating between very similar metals, that’s really powerful,” said Cotruvo. “If we can take lanmodulin and turn it into a manganese-binding protein, then what else can we do?”
Patients-turned-social-media-influencers routinely offer prescription drug advice to their followers and often have close ties with pharmaceutical companies, according to new research the Journal of Medical Internet Research – though they often have good intentions.
In recent weeks, social media has pushed the diabetes drug Ozempic as a weight loss drug, while patients who need the medication to manage their disease have faced global shortages. Those taking it “off-label” to slim down have experienced surprising side-effects, including violent diarrhoea and extreme facial thinning.
The study by University of Colorado Boulder provides some of the first insights into the burgeoning, loosely regulated world of so-called “patient influencers”.
“The bottom line here is that patient influencers act as a form of interactive direct-to-consumer (DTC) advertising, sharing their knowledge and experiences on pharmaceutical drugs with communities of followers in which they wield great influence,” said author Erin Willis, an associate professor of advertising, public relations and media design. “This raises ethical questions that need more investigation.”
A new kind of advertising
Controversial from its start in the 1980s, and still only available in the United States and New Zealand, DTC advertising enables drug companies to target consumers directly, rather than exclusively through physicians. About half of the people who ask their doctor about a drug after seeing a TV ad get it.
With trust in pharmaceutical companies and traditional media declining, drug makers are now turning to real patients as messengers, with companies like Health Union connecting them for partnerships.
Willis conducted interviews with 26 influencers with a range of conditions, including lupus, HIV and chronic migraines. Eighteen of the 26 collaborated with a pharmaceutical company in some way.
Most had between 1000 and 40 000 followers. Such “micro influencers” tend to be less expensive for advertisers to work with than celebrities, and research has shown they have the most influence on purchasing behaviours, said Willis.
Some interviewees posted company press releases directly. Others read studies about drugs and translated results for followers. Some were paid to post content for drug companies.
“Health literacy and digital literacy are both concerningly low in this country,” said Willis, noting that consumers often fail to recognise the difference between a sponsored ad and an altruistic personal post. “The fact that patients with no medical training are broadly sharing drug information should alarm us.”
Good intentions
On the positive side, Willis was heartened by the reasons participants become influencers. Almost all said they were drawn to their roles by a sense that the answers they sought as patients, didn’t exist in other channels.
“I spent a lot of time looking for diabetes information that related to me – an African American woman from the South,” reported one study participant. “I didn’t see what I needed, so I created it.”
Others were motivated by a wish to destigmatise disability in certain communities.
“There’s still not a lot of talk about Latinos and HIV,” said another participant. “When there was information, it wasn’t culturally appropriate.”
Five said they never share information about drugs, stating that they believed it was “borderline unethical.”
Others said they would only post about drugs they personally had been prescribed and taken and always encouraged followers to consult with their doctor. They all said they generally strived to behave ethically.
“It’s comforting that the people we interviewed generally want to stay abreast of the science and be a credible source,” said Willis. “But I also know that doctors go to medical school for a reason.”
Concerns abound
Several influencers reported that followers frequently private message them to get detailed information about dosage and side effects.
“In an online community, there are other people there to say, ‘That’s not true or that’s not what I experienced.'” Willis said. “But with social media, a lot of the conversation happens privately.”
Willis also worries that influencers may stress the upsides of medications without fully disclosing the side-effects. For instance, she references a famously controversial 2015 post by celebrity influencer Kim Kardashian, singing the praises of a “#morningsickness” drug called Diclegis to her tens of millions of followers on Instagram.
The Food and Drug Administration swiftly flagged the post for omitting the drug’s long list of risks, required Kardashian to remove the post and dinged the drug maker with a warning letter. The Federal Trade Commission (FTC) now requires influencers to disclose whether they are paid via hashtags, such as #ad or #sponcon, and the Food and Drug Administration has rules on what can be said on social posts. But those rules are open to interpretation, and videos, disappearing content and direct messaging can be tough to track.
Willis acknowledged that her sample was a small one and that because many of her interviewees were referred to her by Health Union, they likely skew to the responsible side. In future studies, she intends to include broader sample sizes, explore how influencers impact treatment decisions and investigate compensation for and regulations around patient influencers.
Analysts predict the influencer marketing industry as a whole will be valued at $21.1 billion in 2023.
As patient influencers increasingly find their place in it, Willis contends that regulators should work harder to keep up with all the new platforms.
“This is happening, with or without regulation, and people should be aware of it,” Willis said.
A surprising fact is that bitter taste receptors are found not just in the mouth, but elsewhere including the airways. Activating those receptors dilates up lung passageways, making them a potential target for treating asthma or chronic obstructive pulmonary disease (COPD). Now, researchers report in the Journal of Medicinal Chemistry that they have designed a potent and selective compound that could lead the way to such therapies.
Among the 25 different types of bitter taste receptors, the TAS2R14 subtype is one of the most widely distributed in tissues outside the mouth. Scientists are uncertain about the structure of the receptor, and they haven’t identified the particular compound or “ligand” in the body that activates it. However, a few synthetic compounds, such as the nonsteroidal anti-inflammatory drug (NSAID) flufenamic acid, are known to bind to and activate TAS2R14s. But these compounds aren’t very potent, and they don’t have similar structural features. These difficulties make it challenging to create a better ligand. Nevertheless, Masha Niv, Peter Gmeiner and colleagues used flufenamic acid as a starting point to design and synthesise analogues with improved properties. Next, the team wanted to extend that work to develop a set of even better TAS2R14 ligands.
Building on these earlier findings, the researchers made several new variations. They tested these compounds in a cell-based assay that measures receptor activation. This approach revealed that replacing a phenyl ring with a 2-aminopyrimidine and substituting a tetrazole for a carboxylic acid group was a promising strategy. One of the new ligands was six times more potent than flufenamic acid, meaning less of the compound was needed to produce a similar response as the NSAID. This ligand was also highly selective for TAS2R14 compared to non-bitter taste receptors, which could potentially minimise side effects. The researchers speculate that new compounds will help shed light on the structure, mechanism and physiological function of bitter taste receptors and guide development of drug candidates to target them.
Researchers at Northwestern Medicine suggest that pregnant persons should dim the lights in their home and turn off or at least dim their screens (computer monitors and smartphones) a few hours before bedtime to reduce the risk of gestational diabetes mellitus.
In their study published in the American Journal of Obstetrics and Gynecology Maternal Fetal Medicine, women who developed gestational diabetes mellitus in the multi-site study had greater light exposure in the three hours before sleep onset. They did not differ in their light exposure during daytime or sleep or in their activity levels compared to those who did not develop it.
“Our study suggests that light exposure before bedtime may be an under-recognised yet easily modifiable risk factor of gestational diabetes,” said lead study author Dr Minjee, Northwestern Medicine neurologist.
While exposure to light at night before bedtime may be linked to impaired glucose regulation in non-pregnant adults, little is known about the effect of evening light exposure during pregnancy on the risk of developing gestational diabetes.
This is believed to be one of the first multi-site studies to examine light exposure before sleep on the risk of developing gestational diabetes, a serious health complication for mother and child.
‘Alarming’ global rise in gestational diabetes
Gestational diabetes is on the rise in the U.S. and globally. About 4.5% of first-time pregnant women with a baby born between 2011 and 2013 developed gestational diabetes, which has been increasing on average 3.4% per three-year period until 2019. In 2020, the rate of gestational diabetes was 7.8% of all births in the US.
“It’s alarming,” Kim said. “Gestational diabetes is known to increase obstetric complications, and the mother’s risk of diabetes, heart disease and dementia. The offspring also are more likely to have obesity and hypertension as they grow up.”
Data show that women who have gestational diabetes are nearly 10 times more likely to develop type 2 diabetes mellitus compared to those do not have glucose issues during pregnancy, Kim said.
Bright light exposure prior to sleep can come from bright indoor lighting and from device screens.
“We don’t think about the potential harm of keeping the environment bright from the moment we wake up until we go to bed,” Kim said. “But it should be pretty dim for several hours before we go to bed. We probably don’t need that much light for whatever we do routinely in the evening.”
Scientists don’t know which source of bright light causes the problem, but it might all add up, Kim said.
“Try to reduce whatever light is in your environment in those three hours before you go to bed,” Kim said. “It’s best not to use your computer or phone during this period. But if you have to use them, keep the screens as dim as possible,” Kim said, suggesting people use the night light option and turn off the blue light.
If pregnant persons develop gestational diabetes with the first pregnancy, they are more likely to have it with the next pregnancy.
Pre-sleep light exposure increases heart rate, with knock-on effects
Pre-sleep light exposure may affect glucose metabolism through sympathetic overactivity, meaning the heart rate goes up before bed when it should go down. “It seems there is inappropriate activation of the fight or flight response when it is time to rest,” Kim said.
Data shows the sympathetic overactivity may lead to cardiometabolic disease, which is a cluster of conditions including abdominal obesity, insulin resistance, increased blood pressure and an imbalance of lipids, all leading to cardiovascular disease.
The study of 741 women in their second trimester was conducted at eight clinical U.S. sites between 2011 and 2013. The participants’ light exposure was measured by an actigraph worn on their wrists. The women were measured during the second trimester of pregnancy, the time when they receive routine screening for gestational diabetes.
After adjusting separately for age, BMI, race/ethnicity, education, commercial insurance, employment schedule, season, sleep duration, sleep midpoint, sleep regularity index, and daytime light exposure, pre-sleep light exposure remained significantly associated with gestational diabetes.
The growing rate of gestational diabetes has been partially attributed to increasing body mass index and the older age of pregnant persons.
“But even after adjusting for BMI and age, gestational diabetes is still rising,” Kim said. “We have a lot to prove, but my personal worry is that light may be silently contributing to this problem without most people realising the potential harm.”
Losing body weight and exercising also reduce the risk of developing gestational diabetes, which are important but take some effort.
Turning down lights is an easy fix
“Turning down the lights is an easy modification you can make,” Kim said.
“Now I’m the light police at home,” Kim said. “I see all this light I never thought about before. I try to dim the light as much as possible. Just for evening activities such as dinner and bathing the kids, you don’t need bright light.”
“This study highlights the importance of reducing light exposure in the hours before bedtime” said senior author Kathryn Reid, research professor of neurology at Feinberg.
