Category: Medical Research & Technology

Fraud Trial of Theranos Boss Begins

Photo by Tingey Injury Law Firm on Unsplash

On Wednesday, the trial of Elizabeth Holmes, founder of medical technology company Theranos, began. Prosecutors alleged she “lied and cheated” for money and fame.

Ms Holmes faces 12 fraud charges over her role at the failed company which was once worth $9bn, facing up to 20 years in prison if found guilty.

She is accused of deceiving patients and investors about the company’s testing technology, which was claimed to diagnose basic illnesses from a few drops of blood. Her defence team argues that she was naive and her company simply failed.

“Failure is not a crime. Trying your hardest and coming up short is not a crime,” said defence lawyer Lance Wade in his opening statement on Wednesday.

Former Theranos executive Ramesh “Sunny” Balwani faces the same charges next year. He was romantically involved with Ms Holmes.

Ms Holmes, who founded Theranos in 2003 aged 19, was dubbed the world’s youngest self-made female billionaire and hailed as the “next Steve Jobs”.

In 2015 and 2016, investigations by the Wall Street Journal revealed Theranos’ blood-testing devices did not work and the company was doing most of its testing on commercially available machines made by other manufacturers. She initially denied these reports.

Prosecutor Robert Leach alleges that, after running out of funds, Ms Holmes and Mr Balwani turned to fraud in 2009, lying about the tests and exaggerating the firm’s performance. Mr Leach said this included falsely claiming the tests were vetted by Pfizer and being used by the US military.

The case will probably take months and Ms Holmes will likely take the stand — a necessary gamble in the face of overwhelming evidence that the technology did not work.

Ms Holmes “dazzled” Walgreens into using the company’s services, and the company brought her fame.

“She had become, as she sought, one of the most celebrated CEOs in Silicon Valley and the world. But under the facade of Theranos’ success there were significant problems brewing.”

 The defence’s Mr Wade said Ms Holmes “naively underestimated” the business challenges but did not attempt to defraud investors. Ms Holmes has also alleged years of emotional and psychological abuse by Mr Balwani, who has denied the allegations. She is likely to testify as to how this affected her.

Source: BBC News

New Medical Emoji Urged for Patient Communication

Photo by visuals on Unsplash

Emoji, those colourful symbols we use in WhatsApp and other communication applications, could be a valuable medical tool which lets patients better communicate symptoms, concerns, and other clinically relevant information, researchers argue.

In a commentary in the Journal of the American Medical Association, senior author Shuhan He, MD, an emergency department attending, advises that each medical discipline start to come up with its own unique set of iconography for official adoption and incorporation into everyday practice.

“The need to listen to patients is at the core of our mission as physicians, and the use of emoji is a great opportunity to take communication to another level,” said Dr He. “Emoji could be particularly important in treating children with still-developing language skills, people with disabilities that impair their ability to communicate, and the many patients who speak a different language.”

While around 3500 emoji are currently within the domain of the Unicode Consortium – the nonprofit organisation that maintains text standards across computers – only about 45 emoji can be considered relevant to medicine. The first, introduced in 2015, were the syringe and the pill. Apple added emoji in 2017 to represent people with disabilities, followed by symbols of the stethoscope, bone, tooth and microbe in 2019. He was co-creator of the anatomical heart and the lung emoji introduced globally in 2020 and is now working with colleagues, as well as with a wide range of medical societies and organisations to advocate for an additional 15 medically related emoji.

“It’s tempting to dismiss emoji as a millennial fad, but they possess the power of standardisation, universality and familiarity, and in the hands of physicians and other health care providers could represent a new and highly effective way to communicate pictorially with patients,” said Dr He. In emergency medical settings where time is critical, emoji could lead to a point-and-tap form of communication that could facilitate important clinical decisions, he adds. The tiny graphic symbols which now span all digital platforms – from mobile to tablet to desktop – could also have utility as annotations to hospital discharge instructions, which are often confusing if not incomprehensible to some patients.

The recent surge of telemedicine presents a great opportunity for medical emojis. It is well suited for patients visually conveying to healthcare providers the intensity of pain they have experienced over time, and for those providers to incorporate it into digital health records.

His research is on emoji to help patients and doctors communicate common symptoms – such as mobility, mood, and duration and quality of pain – that are associated with various diseases and conditions. “It’s clear that emoji have become part of the global, mainstream conversation, and that medical societies and physician committees and organisations need to take them seriously,” said Dr He. “Which means they should be determining now which emoji would best serve the interests of their patients, building consensus around the medical accuracy of these emoji, then working to get them approved through the global standard-setting body and working through the long adaptation and implementation process.”

Source: EurekAlert!

Thrombin’s Involvement with Coagulation Reconsidered

Source: NIH

After 20 years of research, an established truth of how thrombin interacts with coagulation has been overturned.

“It has been said that an established truth in medicine lasts for about 10 years. It is probably the case that many truths last longer, but on the other hand, the time that different truths stand is constantly shrinking. This is because our perception of reality is changing rapidly, in step with new research,” said Tom Eirik Mollnes, Professor at the University of Oslo and Oslo University Hospital.

Based on more than 20 years of work to develop a whole blood model, Mollnes and colleagues have recently disproved an established truth about the immune system.

“There was an established truth in the literature for many years that a protein in the coagulation system called thrombin could activate a protein called C5 in the complement system,” Prof Mollnes said.

However, Prof Mollnes and his colleagues doubted whether the methods used in the studies were reliable.

“The notion that the protein thrombin could activate the protein C5 was only shown in so-called purified systems. That is, the proteins were taken out of their natural context,” he explained.

The researchers thought that the results would possibly be different if you looked at how the proteins work in their natural environment in the blood.

“The modified model made it possible to study the connection between the various proteins and defence systems as close to reality as possible,” Prof Mollnes explained. “Using the new model, we clearly showed that the previous findings were incorrect. We showed that the proteins changed structure and function during the purification, and that this was the reason for the former findings.”

When the proteins were in their natural environment in the blood, thrombin did not activate the protein in the complement system. Thus, the researchers had disproved the established truth.

“Many findings have been published in purified systems that are not representative of reality,” he said. “You can say that Gro Harlem Brundtland’s statement that “everything is connected to everything” is a very good description of how biology and the human body work. Therefore, it is important to use methods that make it possible to look at how different systems in the body interact and cooperate.”

The whole blood model makes such methods possible, and the model can be used widely. The whole blood model can, by and large, be used to study all the substances and biological systems in the blood.

Professor Mollnes therefore considers the model to have great potential.

“With the whole blood model, we have contributed to something that we will not only benefit from in our own laboratory, but that can be an asset to research groups in a number of fields,” he said.

It takes time to develop new models, and it was a long uphill battle for Prof Mollnes and his research group. Even so, the researchers have now received recognition for their work from the research community. The article got a recommendation by the editors of The Journal of Immunology, [PDF] in which it was published, as a ‘Top Reads Selection’.

“Changing so-called established truths is not easy, and we had to go through many rounds, with a number of experiments, to gain acceptance for our findings. That is why our work was especially recognised,” he concluded.

Source: University of Oslo

MRI and Massage Stones Help Unlock Mystery of Sensory Associations

Photo by engin akyurt on Unsplash

By using hot and cold massage stones, scientists have found that the brain’s prefrontal cortex conjures up sensations based on other sensory information, such as feeling warmth when viewing a beach.

Publishing their findings in The Journal of Neuroscience, the researchers investigated patterns of neural activity in the prefrontal cortex as well as the other regions of the brain known to be responsible for processing stimulation from all the senses and discovered significant similarities.

“Whether an individual was directly exposed to warmth, for example, or simply looking at a picture of a sunny scene, we saw the same pattern of neural activity in the prefrontal cortex,” said Dirk Bernhardt-Walther, an associate professor in the department of psychology in the Faculty of Arts & Science, and coauthor of a study published last week in the Journal of Neuroscience describing the findings. “The results suggest that the prefrontal cortex generalizes perceptual experiences that originate from different senses.”

To understand how the human brain processes the torrent of information from the environment, researchers often study the senses in isolation, with much prior work focused on the visual system. Bernhardt-Walther says that while such work is illuminating and important, it is equally important to find out how the brain integrates information from the different senses, and how it uses the information in a task-directed manner. “Understanding the basics of these capabilities provides the foundation for research of disorders of perception,” he said.

Capturing brain activity with functional magnetic resonance imaging (fMRI), the researchers conducted two experiments with the same participants, based on knowing how regions of the brain respond differently depending on the intensity of stimulation.

In the first, the participants viewed images of various scenes, such as beaches, city streets, forests and train stations, and were asked to judge if the scenes were warm or cold and noisy or quiet.

For the second experiment, participants were first handed a series of massage stones that were either heated to 45C or cooled to 9C, and later exposed to a variety of sounds such as birds, people and waves at a beach.

“When we compared the patterns of activity in the prefrontal cortex, we could determine temperature both from the stone experiment and from the experiment with pictures as the neural activity patterns for temperature were so consistent between the two experiments,” said lead author of the study Yaelan Jung, who recently completed her PhD at U of T working with Bernhardt-Walther and is now a postdoctoral researcher at Emory University.

“We could successfully determine whether a participant was holding a warm or a cold stone from patterns of brain activity in the somatosensory cortex, which is the part of the brain that receives and processes sensory information from the entire body – while brain activity in the visual cortex told us if they were looking at an image of a warm or cold scene.”

“Overall, the neural activity patterns in the prefrontal cortex produced by participants viewing the images were the same as those triggered by actual experience of temperature and noise level,” said Dr Jung.

This opens up insights into how the brain processes and represents complex real-world attributes that span multiple senses, even without directly experiencing them.

“In understanding how the human brain integrates information from different senses into higher-level concepts, we may be able to pinpoint the causes of specific inabilities to recognise particular kinds of objects or concepts,” said Bernhardt-Walther.

“Our results might help people with limitations in one sensory modality to compensate with another and reach the same or very similar conceptual representations in their prefrontal cortex, which is essential for making decisions about their environment.”

Source: University of Toronto

New Prosthetic Arm Restores Normal Movements

A prosthetic arm being fitted. Source: This is Engineering on Unsplash

Researchers have developed a bionic arm for patients with upper-limb amputations that allows wearers to think, behave and function like a person without an amputation.

The arm combines three important functions – intuitive motor control, touch and grip kinaesthesia, the intuitive feeling of opening and closing the hand. The developers, led by Clevelend Clinic, published their findings in Science Robotics.

“We modified a standard-of-care prosthetic with this complex bionic system which enables wearers to move their prosthetic arm more intuitively and feel sensations of touch and movement at the same time,” said lead researcher Paul Marasco, PhD, associate professor  in Cleveland Clinic Lerner Research Institute’s Department of Biomedical Engineering. “These findings are an important step towards providing people with amputation with complete restoration of natural arm function.”

The system is the first to test all three sensory and motor functions in a neural-machine interface simultaneously in a prosthetic arm. The neural machine interface sends impulses from the brain to the arm and sensory information back to the brain.

“Perhaps what we were most excited to learn was that they made judgments, decisions and calculated and corrected for their mistakes like a person without an amputation,” said Dr Marasco. “With the new bionic limb, people behaved like they had a natural hand. Normally, these brain behaviors are very different between people with and without upper limb prosthetics.
The researchers tested their new bionic limb on two study participants with upper limb amputations who had previously undergone targeted sensory and motor reinnervation -procedures that establish a neural-machine interface by redirecting amputated nerves to remaining skin and muscles. 

In targeted sensory reinnervation, touching the skin with small robots activates sensory receptors that enable patients to perceive the sensation of touch. In targeted motor reinnervation, when patients think about moving their limbs, the reinnervated muscles communicate with a computerised prosthesis to move in the same way. Additionally, small, powerful robots vibrate kinesthetic sensory receptors in those same muscles which helps prosthesis wearers feel that their hand and arm are moving. The new prosthetic arm feels grip movement sensation, touch on the fingertips, and is controlled intuitively by thinking. Cameras lets the computer see the prosthetic’s position.

While wearing the advanced prosthetic, participants performed tasks reflective of basic, everyday behaviours that require hand and arm functionality, which were compared to people with traditional prosthetics and people without amputations.

According to Dr Marasco, because the limb lacks sensation, people with traditional prosthetics behave differently than people without an amputation when performing tasks. For example, traditional prosthesis wearers must constantly watch their prosthetic while using it, and have difficulty correcting for the correct amount of force needed.

The researchers could see that the study participants’ brain and behavioural strategies changed to match those of a person without an amputation. They no longer needed to watch their prosthesis, they could locate things without looking, and they could more effectively correct mistakes.

“Over the last decade or two, advancements in prosthetics have helped wearers to achieve better functionality and manage daily living on their own,” said Dr. Marasco. “For the first time, people with upper limb amputations are now able to again ‘think’ like an able-bodied person, which stands to offer prosthesis wearers new levels of seamless reintegration back into daily life.”

Source: Cleveland Clinic

How Blood Vessels Change Permeability

Source: Wikimedia CC0

Researchers have made steps toward understanding how blood vessels change permeability, and how they might intervene to restore blood vessel integrity during sepsis, trauma or other conditions.

Sepsis occurs when a patient’s over-activated immune system harms their own tissues. As a result, blood vessels can become ‘leaky’ and can’t adequately supply major organs. The condition is notoriously difficult to treat, and there are no drugs that help stabilize the cell barrier that lines blood vessels.

A protein, HSP27, was previously found by researchers at University of California San Diego to be involved in regulating blood vessel leakage. To help break down or build up blood vessel barrier, cells add and remove chemical tags on HSP27.

The study, reported in Science Signaling, provides new potential targets for the development of drugs that shore up blood vessel barriers, preventing fluid loss.

“This new information will help us home in on the root cause of leaky blood vessels, rather than taking a broad strokes approach that may have many off-target effects,” said senior author JoAnn Trejo, Ph.D., professor of pharmacology and assistant vice chancellor of the Office of Health Sciences Faculty Affairs at UC San Diego School of Medicine.

Blood vessel barriers need to be permeable enough to allow immune cells to squeeze out to reach the site of an infection, for example, but not so much that the situation becomes life-threatening. HSP27 binds to proteins that help form the cell’s “skeleton.” Prof Trejo and colleagues suspect that’s how HSP27 affects blood vessel permeability: by reinforcing the skeleton of cells that maintain the barrier.

Prof Trejo has long studied G-protein-coupled receptors (GPCRs), proteins that are embedded in cell membranes and act as signal transducers for cells. About a third of all therapeutic drugs on the market work because they influence GPCR signals.

In their latest study, the team found that during inflammation, GPCRs tell enzymes called kinases to add chemical (phosphate) tags to HSP27. The tags perturb HSP27’s structure in a way that disrupts blood vessel barriers. When HSP27 reassembles, the barriers recover. The researchers validated their lab studies in mice, where they found that inhibiting HSP27 increases blood vessel leakage.

One problem in targeting GPCRs to treat a disease is that most act as master regulators, influencing many different cell functions. Inhibiting one GPCR may therefore have many unintended consequences. By aiming not at the master GPCR but at individual targets upon which it acts, such as HSP27, Trejo’s team is hoping to enable the development of blood vessel barrier-stabilising drugs that have greater precision and fewer side effects.

“It’s become apparent that you can develop different molecules that can bind to receptor and ‘bias’ them — make them signal in a very specific way to some pathways but not others,” Prof Trejo said. “It’s what we call biased agonism, and it’s a huge advantage for drug development. It means we can develop not just an on/off switch, but a drug that can switch a receptor ‘off’ or eight different types of ‘on.’ We want to be able to tweak which pathways are on and not touch others.”

The team plans to explore additional cell signaling pathways that helps blood vessels build resistance to injury and inflammation.

Source: UC San Diego

An Oxygen-delivering Hydrogel for Diabetic Foot Ulcers

Photo by Denes Kozma on Unsplash

A quarter of people with diabetes develop foot ulcers, which are slow to heal due to hypoxic conditions in the wound from impaired blood vessels and increased inflammation. These wounds can become chronic, leading to poor quality of life and possibly amputation.

Jianjun Guan, professor of mechanical engineering and materials science at the McKelvey School of Engineering at Washington University in St. Louis, has developed a hydrogel that delivers oxygen to a wound and decreases inflammation, helps to remodel tissue and speeds up healing. The results are published in Science Advances

Prof Guan’s new hydrogel uses microspheres to gradually release oxygen to interact with the cells by means of an enzyme coating that converts the microsphere’s contents into oxygen. In this way, the hydrogel delivers oxygen over two weeks, reducing inflammation and promoting healing.
“The oxygen has two roles: one, to improve skin cell survival under the low-oxygen condition of the diabetic wound; and two, oxygen can stimulate the skin cells to produce growth factors necessary for wound repair,” Prof Guan said.

Source: Washington University in St. Louis

Drone-delivered Defibs Beat Ambulances to Cardiac Arrests

Photo by David Bartus from Pexels

In a unique pilot project in Sweden, drones were used to deliver defibrillators to real-life alerts of suspected cardiac arrest. The drones were dispatched in more than a fifth of the emergencies and arrived on target and ahead of the ambulance in most cases. 

”This is the first time in the world that a research group can report results from a study where drones flew defibrillators to location of real-life alerts of suspected cardiac arrest,” says lead researcher Andreas Claesson, associate professor at the Center for Resuscitation Science at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.

With sudden cardiac arrest, every minute counts. Currently, the odds of surviving an out-of-hospital cardiac arrest are 10 percent. However, with early CPR and a shock from an automated external defibrillator (AED), the chances of survival could reach 50-70 percent but response time needs to improve. In 2019 the median response time from alert to ambulance arrival for out-of-hospital cardiac arrest (OHCA) in Sweden was 11 minutes.  
To try and reach cardiac arrest victims sooner, researchers investigated using the rapid dispatch of drone-carried defibrillators in parallel with ambulances. Drones are already used in some countries to dispatch medicines and medical supplies to remote rural regions, The study, conducted in mid-2020 in western Sweden, describes an integrated method where emergency operators, drone pilots and air traffic control worked together to facilitate the dual response.

The drones took off in response to 12 out of 53 alerts of suspected cardiac arrest over a four-month period, successfully delivering an AED to the site in 11 of those cases. In seven of those cases, the drones arrived before the ambulance, with a median time benefit of 1 minute and 52 seconds. However, no drone-delivered defibrillators were attached to the patients before ambulances arrived.

“Even if none of the AEDs were used this time, our study shows that it is possible to use drones to transport defibrillators in a safe way and with target precision during real-life emergencies,” said first-author Sofia Schierbeck, PhD student at the Center for Resuscitation Science at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet. “A precondition for their future use is that the dispatcher takes initiative and instructs people on site to quickly collect and attach the AED in order to help the person with cardiac arrest.”

More work is needed to increase the dispatch rate and time benefits. For instance, in 2020 the drones were grounded if it was dark, rainy or the winds were too strong. The software system was also configured to avoid routes above densely populated areas, meaning that some alerts were too far out of range.

“Since this study was completed, we have identified several areas of improvement,” Andreas Claesson said. “In April this year, we began a follow-up study with a more optimised system. In that study, we want to test if we can use the drones in more alerts and reduce the response time further and thereby increase the time benefit as compared to the ambulance. Every minute without treatment in the early stages reduces the chance of survival by around 10 percent, and that is why we believe this new method of delivery has the potential to save lives.”

The results are published in the European Heart Journal.

Source: Karolinska Institute

Human Breast Milk Could Yield Antibiotic Secrets

Researchers believe that antibacterial properties of sugars in human breast milk could be harnessed for new antimicrobial therapies.

Group B Streptococcus (GBS) bacteria are a common cause of blood infections, meningitis and stillbirth in newborns, and are becoming resistant to antibiotics. Researchers have now discovered that human milk oligosaccharides (HMOs), short strings of sugar molecules abundant in breast milk, can help prevent GBS infections in human cells and tissues and in mice. This might yield new antibiotic treatments, the researchers believe. 

“Our lab has previously shown that mixtures of HMOs isolated from the milk of several different donor mothers have antimicrobial and antibiofilm activity against GBS,” says Rebecca Moore, who is presenting the work at a meeting of the American Chemical Society (ACS). “We wanted to jump from these in vitro studies to see whether HMOs could prevent infections in cells and tissues from a pregnant woman, and in pregnant mice.” Moore is a graduate student in the labs of Steven Townsend, PhD, at Vanderbilt University and Jennifer Gaddy, PhD, at Vanderbilt University Medical Center.

According to the US Centers for Disease Control and Prevention, about 2000 babies in the U.S. get GBS each year, with 4-6% of them dying from it. The bacteria are often transferred from mother to baby during labour and delivery. An expectant mother who tests positive for GBS is usually given intravenous antibiotics during labor to help prevent early-onset infections, which occur during the first week of life. Notably, late-onset infections (which happen from one week to three months after birth) are more common in formula-fed than breastfed infants, suggesting breast milk has factors which could help protect against GBS. If so, the sugars could be a replacement for current antibiotics which are steadily becoming less effective.

The researchers studied the effects of combined HMOs from several mothers on GBS infection of placental macrophages and of the gestational membrane. “We found that HMOs were able to completely inhibit bacterial growth in both the macrophages and the membranes, so we very quickly turned to looking at a mouse model,” Moore says. They examined whether HMOs could prevent a GBS infection from spreading through the reproductive tract of pregnant mice. “In five different parts of the reproductive tract, we saw significantly decreased GBS infection with HMO treatment,” Moore notes.

To determine which HMOs and other oligosaccharides have these antimicrobial effects and why, the researchers made an artificial two-species microbiome with GBS and the beneficial Streptococcus salivarius species growing in a tissue culture plate, separated by a semi-permeable membrane. Then, the researchers added oligosaccharides that are commonly added to infant formula, called galacto-oligosaccharides (GOS), which are derived from plants. In the absence of the sugar, GBS suppressed the growth of the “good” bacteria, but GOS helped this beneficial species grow. “We concluded that GBS is producing lactic acid that inhibits growth, and then when we add the oligosaccharide, the beneficial species can use it as a food source to overcome this suppression,” Moore explained.
The first HMOs tested did not have this effect, but Townsend says it’s likely that one or more of the over 200 unique sugars in human milk will show activity in the artificial microbiome assay. There are likely two reasons why HMOs can treat and prevent GBS infection: they prevent pathogens from sticking to tissue surfaces and forming a biofilm, and they could also act as a prebiotic by promoting good bacteria growth.

“HMOs have been around as long as humans have, and bacteria have not figured them out. Presumably, that’s because there are so many in milk, and they’re constantly changing during a baby’s development,” Townsend said. “But if we could learn more about how they work, it’s possible that we could treat different types of infections with mixtures of HMOs, and maybe one day this could be a substitute for antibiotics in adults, as well as babies.”

Source: American Chemical Society

A Leak-proof, Biocompatible Intestinal Patch

Researchers at Empa have developed a patch that stably seals two sutured pieces of intestine and thus prevents dangerous leaks.

A burst appendix or a life-threatening intestinal volvulus are emergencies that need to be treated by surgeons immediately. However, operations carry risks: highly acidic digestive juices and intestinal bacteria can leak out, causing peritonitis and sepsis.

Sealing sutured tissue with a plaster has already been tried, but the first were not well tolerated or were even toxic. Currently, these plasters are made of biodegradable proteins, which have variable clinical results. These is because they are mainly intended to support the healing process, and dissolve too quickly when in contact with digestive juices and don’t always hold tight. “Leaks after abdominal surgery are still one of the most feared complications today,” explained Empa researcher Inge Herrmann, who is also professor for nanoparticulate systems at ETH Zurich.

Searching for a material that could reliably seal intestinal injuries and surgical wounds, Hermann’s team found a synthetic composite material made up of four acrylic substances that, together, form a chemically stable hydrogel. Additionally, the patch actively cross-links with the intestinal tissue until it is fluid-tight. The quadriga of acrylic acid, methyl acylate, acrylamide and bis-acrylamide works in perfect synergy, as each component conveys a specific feature to the final product: a stable bond to the mucosa, the formation of networks, resistance to digestive juices and hydrophobicity. This new technology is detailed in Advanced Functional Materials.

In lab experiments, the researchers found the polymer system met their expectations. “Adhesion is up to ten times higher than with conventional adhesive materials,” said researcher Alexandre Anthis from Empa’s Particles-Biology Interactions lab in St. Gallen. “Further analysis also showed that our hydrogel can withstand five times the maximum pressure load in the intestine.” The material’s design uses its tailored effect: The rubbery composite selectively reacts with digestive juices that might leak through intestinal wounds, expands and closes all the more tightly. The inexpensive, biocompatible super glue, could thus shorten hospital stays and save healthcare costs, and Anthis is making plans to bring it to market.

Source: Empa