New evidence shows higher oxygen concentrations may help prevent deaths of preterm babies
Photo by Hush Naidoo on Unsplash
Giving very premature babies high concentrations of oxygen soon after birth may reduce the risk of death by 50%, compared to lower levels of oxygen says new research led by University of Sydney researchers.
Premature babies sometimes need assisted breathing because their lungs haven’t finished developing, so doctors may give them supplemental oxygen via a breathing mask or breathing tube.
The study, published in JAMA Pediatrics, examined clinical trial data and outcomes of over one thousand premature babies who were given different oxygen concentrations. This included low concentrations of oxygen (~30%), intermediate (~50–65%) or high (~90%).
The study found for babies born prematurely, at less than 32 weeks starting resuscitation with high concentrations of oxygen (90% or greater), could increase chances of survival compared to low levels (21–30%).
When a doctor provides oxygen to babies that need help breathing, there is a device that regulates how oxygen is mixed together to reach the desired concentration. The researchers believe higher initial levels of oxygen may jump-start independent breathing, but more research is required to explore the underlying cause for this effect.
The researchers emphasise that additional large studies will be important to confirm this finding, and that even when starting with high oxygen, it needs to be adjusted to lower levels quickly to avoid hyperoxia (oxygen poisoning).
How the oxygen is delivered during the first 10 minutes of the infant’s life is critical. Doctors may give the baby high levels of oxygen at the start but then monitor vital signs and continually adjust the oxygen to avoid over or under exposure.
If confirmed in future studies, the findings challenge current international recommendations that suggest giving preterm babies the same amount of oxygen as babies born at term, 21%–30% oxygen (room air), rather than extra oxygen.
This study also demonstrates that there may not be a one-size-fits-all approach, and babies born prematurely may have different needs than babies born at term.
“Ensuring very premature infants get the right treatment from the beginning sets them up to lead healthy lives. There is no better time to intervene than immediately after birth,” said lead author Dr James Sotiropoulos from the University of Sydney’s NHMRC Clinical Trials Centre.
“The goal is to find the right balance – how do we give enough oxygen to prevent death and disability, but not damage vital organs.”
“Whilst promising and potentially practice-changing, these findings will need to be confirmed in future larger studies.”
Historically, oxygen with a 100% concentration was used to resuscitate all newborn infants. But due to studies that found high concentrations of oxygen over time can lead to hyperoxia and subsequent organ damage, in 2010 it prompted changes in international treatment recommendations for the use of blended oxygen (starting with low oxygen) for preterm infants.
Hyperoxia still a danger
However, researchers say the change was mainly based on evidence for full-term infants, who have fully developed lungs and who are often not as sick as premature infants. To date, there is little conclusive evidence to guide best practice for premature infants. The researchers emphasise the findings should not minimise the dangers of hyperoxia.
“The debate around exactly how much oxygen is best for extremely premature babies is still ongoing but, ultimately, everyone has the same shared goal of determining the best treatment for newborns,” said Dr Anna Lene Seidler from the NHMRC Clinical Trials Centre.
“Our findings, together with all the other research that is currently happening, may help the most vulnerable preterm infants have the best chance of survival.”
“We are very lucky to work with a highly collaborative international group on this question, some of whom have been studying it for decades. The group’s diverse expertise and experience is a major strength of this work,” said Dr Sotiropoulos.
Nutritionists generally advise everyone to eat more dietary fibre, but a new study suggests that its effects on health can vary, suggesting that recommendations should be tailored to each individual’s gut microbiome. The study, published in Gut Microbes, focused on resistant starch, a category of dietary fibre found in such foods as bread, cereals, green bananas, whole-grain pasta, brown rice and potatoes.
The researchers identified the gut microbe species that change in response to two different types of resistant starch. They found evidence that each individual may have a unique response to eating a resistant starch, with some people benefiting and others experiencing little or no effect. The reason for the variation appears tied to the level of diversity and composition of a person’s gut microbiome.
“Precision nutrition definitely has a use in determining what dietary fibre we should tell people to eat,” said Angela Poole, assistant professor of molecular nutrition and senior author of the study.
“This is critical because we’ve had public messaging advising people to eat more dietary fibre for decades,” Poole said. “At the same time, less than 10% of people eat the recommended intake. Since there are many different types of dietary fibre and carbohydrates, a better strategy would be to collect data on each person and tell them which dietary fibre they can eat to get the most bang for their buck.”
Resistant starch comes in five types, and resists degradation by human digestive enzymes until it reaches the gut. There, it acts as a substrate for certain gut microbes to produce short chain fatty acids, which are important in signaling pathways that regulate glucose and lipid metabolism. Multiple microbe species may work together to create the fatty acids.
In the study, Poole and colleagues tested three dietary treatments on 59 participants over seven weeks.
The team had three different types of crackers manufactured. Two crackers had the same ingredients, except one contained resistant starch type 2, which occurs naturally, and the other contained resistant starch type 4, which is human-made. A third control cracker was digestible by human enzymes, similar to white bread, and the researchers expected none of the bacteria to act on the control.
Subjects were then divided into two groups. The first group ate the resistant starch type 2 cracker first, followed by the control, and then resistant starch type 4. Each cracker type was eaten for 10 days, with five days of no cracker consumption between treatments. The second group reversed the order, also with the control in the middle.
They then sequenced the microbiomes of each participant before and after each treatment. For resistant starch type 2, more than 30 bacteria changed in abundance, including Ruminococcus bromii, which is considered a keystone resistant starch degrader in the human gut. For type 4, more than 20 bacteria changed. And for the control, nothing changed.
“For the resistant starch crackers, we could detect that 20 or 30 of them were changing, but how much they changed and whether they changed at all, for each of those bacteria, depended on the person,” Poole said.
Similarly, each resistant starch type changed different short chain fatty acids, with variable levels of fatty acid increases and decreases based on the individual. For resistant starch type 2, the researchers identified a subset of 13 bacteria that predicted change in amounts of propionate, a type of short chain fatty acid. Also for resistant starch 2, by knowing the diversity of an individual’s gut microbiome, the researchers could roughly predict if two types of short chain fatty acids (acetate and butyrate) were going to increase.
The most surprising result was that the control digestible cracker led to the greatest gains of short chain fatty acids. More work is needed to understand why, but Poole suspects that the order of cracker consumption was key to the result. Since many microbes are involved in making short chain fatty acids, she hypothesises that eating a resistant starch first primed the gut to produce the fatty acids when that person ate the digestible starch.
“That’s one of the major takeaways, maybe I can get away with eating a French baguette some of the time, and it may be better than just eating whole grain all the time,” Poole said. “But I have to test that, and it probably varies between people.”
Dr Tim Forgan at the surgeon’s console of the da Vinci robotic system. (Photo: Biénne Huisman/Spotlight)
By Biénne Huisman
Within South Africa’s beleaguered public health sector – unsettled by budget cuts, understaffing, and divisive NHI legislation – cutting edge surgical robots that have been used to perform more than 600 surgeries at two Cape Town public hospitals are beacons of excellence that offer a glimmer of hope. Spotlight’s Biénne Huisman visited Dr Tim Forgan at Tygerberg Hospital to learn more.
Cutting edge robotic surgery might not immediately come to mind when one thinks of public hospitals, but in a first for public healthcare in South Africa, such systems are being used at two hospitals in the Western Cape.
The da Vinci Xi systems enable surgeons to control operations from a console – steering three arms with steel “hands” equipped with tiny surgical instruments; plus a fourth arm bearing a video camera (the laparoscope). The system translates a surgeon’s hand movements in real time, with enhanced precision, range and visuals, compared to manual surgery.
“It really is next level, it feels like you’re inside the patient,” says colorectal specialist Dr Tim Forgan, Tygerberg Hospital’s da Vinci robotics coordinator. “With this technology we can operate so much finer. You can see ten times better with this robot than with the naked eye; you can see tiny, tiny nerves you wouldn’t normally see. And you can manoeuvre surgical instruments so much better. Because of that, people have way better function after the procedure.”
He explains that the technology allows major surgery to be completed through small incisions – instead of larger cuts made by a doctor’s hand – leading to less bleeding and a faster recovery time.
Over 600 surgeries in two years
Lorraine Gys from Phillipstown in the Northern Cape can attest. On 22 February 2022, the 65-year-old pensioner became the first patient to undergo da Vinci robotic surgery in South Africa’s public sector. Forgan was behind the console, at Tygerberg Hospital.
Gys tells Spotlight: “The next day the sisters offered to wash me, I said to them ‘no, I’m not helpless.’ My recovery was very quick. I was up and about in no time, while the other patients had to be assisted. I was discharged on day four, and back at home I could even continue doing my own chores.”
Two years later, Gys is cancer free. The mother of three, who now lives in Eerste River, recalls how she made news headlines: “Before the operation, Dr Forgan explained everything to me. They asked my permission, saying that media will be there and the [provincial health] minister.”
Indeed, on the day Forgan operated on Gys, removing a cancerous rectal tumour, he was joined in theatre by several onlookers including former Western Cape MEC of Health and Wellness Nomafrench Mbombo.
“Yes it was a circus,” says Forgan, laughing. “A whole bunch of people watching me operate, quite bloody nerve-wracking. Fortunately I’m experienced at having lots of students around watching; plus performing surgery is just so immersive, everything else fades out.”
On that day, also in the operating room was colorectal surgeon Dr Roger Gerjy, keeping an eye. “He’s a very well-known robotic surgeon; a Swedish surgeon who works in Dubai,” says Forgan. “And if there was a problem, Roger would’ve taken over. He was also there to impart tips and tricks: move the instrument like this, shape it like a hockey stick; because with the robot it’s like having your whole arm inside [the body]. He’d give me advice on what to do with my extra floating arm – where to place it and how to manipulate it – because remember you’re controlling three arms at a time.”
Since 2022, the da Vinci robots installed at Cape Town’s two tertiary hospitals: Groote Schuur and Tygerberg, have enabled over 600 minimally invasive surgeries – including colorectal operations, prostatectomies, cystectomies (bladder removal surgery), and gynaecological procedures to treat endometriosis.
Groote Schuur Hospital has the other da Vinci Xi system run by Western Cape public healthcare
A spokesperson for the Western Cape Ministry of Health and Wellness, under former MEC Mbombo, Luke Albert explains: “We can see the immense impact it has for patients and the health system. For example, a traditional open cystectomy patient would require three days of ICU stay, as well as two weeks of hospital stay to recuperate. During this time, on average, 42% of patients require blood transfusions and almost 20% need total parenteral nutrition (when a patient is fed intravenously). A patient undergoing robotic surgery for a cystectomy requires no ICU stay and goes straight to a general ward for no more than six days on average, with no blood transfusions needed.”
Where the money came from
Asked how the department was able to afford R40 million per system for these machines in the context of severe budget cuts, Albert says: “The purchase was applicable to 2021/22 and not the current financial year; with all provincial health departments currently managing the effects of budget cuts.”
Asked the same question, Forgan explains the investment derived from surplus budget discovered within the throes of the COVID-19 pandemic: “There was a surplus because certain services just couldn’t be done. I mean, for us, we couldn’t do elective surgery. And how state funding works; if you don’t spend your [provincial] budget within the financial year, it goes back to central government.”
What it looks like
On a Friday afternoon at Tygerberg Hospital, Forgan is guiding Spotlight along corridors and up grey linoleum stairs, to the theatre where the da Vinci system is used. Dressed in black surgical scrubs bearing his name and a cap; on his feet Forgan is wearing bright pink crocs. In passing, he waves hello to fellow healthcare staff.
Inside the small blindingly white room, Forgan points out the three core components of the da Vinci system. There is a console with two control levers similar to refined joysticks – he demonstrates how to delicately hold them between forefingers and thumbs – a patient-side cart with four interactive metal arms (they are disposable; each arm can be used on twelve patients), and another trolley with a television screen. All connected by blue fibre optic cables.
As we speak, nurses arrive in the theatre, preparing it for upcoming gynaecology procedures scheduled for Monday. Forgan greets them, then continues to expand on his passion for colorectal surgery.
“With colorectal surgery, there’s a high rate of complications, but I really enjoy it, I really enjoy my job. When you have a successful outcome, saving a person from their cancer and prolonging their life through your intervention, that is the reward. Colorectal cancer is a very unpleasant disease, and operating like this can make one hell of a difference in a patient’s life.”
Colorectal cancer on the increase
Forgan adds that colorectal cancer is on the increase: “There aren’t many colorectal surgeons in South Africa, with a dire need for people to operate in this subspecialty. I mean, there are so few of us, we’re all on a WhatsApp group.”
Colorectal or colon cancer is the second most common cancer in South African men (following prostate cancer), and the third most common cancer in women (following breast and cervical cancer), according to the Cancer Association of South Africa.
Originally from Johannesburg, Forgan attended medical school at the University of the Witwatersrand. He qualified as a general surgeon at Stellenbosch University, sub-specialising in colorectal surgery at the University of Cape Town, before studying minimally invasive colorectal surgery at the Academic Medical Centre in Amsterdam.
He is also president of the South African Colorectal Society and runs a part-time private practise with his Tygerberg colleague, Dr Imraan Mia, at Cape Town’s Christiaan Barnard Hospital, where he has 32 all five-star Google reviews.
‘Early adopter’
Forgan considers himself an early adopter. But learning to use the da Vinci system did not happen overnight.
“We trained for ages,” he says. “On the surgical console there’s a simulator, so you spend hours and days and days doing procedures, over and over and over again. You have to get over 95% for each one of the procedures, before you can move on to the next skill.
“Then it’s how to use the machine, how to put it together, what to do if there’s an emergency; what if there’s a power failure and the machine stops working? How to safely remove it from the person. Then we went to the University of Lyon [in France] for two days of hands-on robotics training. And then a proctor – an international expert – comes to your theatre and does the procedures with you. So that was Dr Roger Gerjy, and that’s when we did Lorraine…”
First introduced by American biotechnology company Intuitive Surgical in 1999, the da Vinci Xi systems have sparked some liability lawsuits. An article from the Tampa Bay Times in February cites a lawsuit filed at the United States District Court in West Palm Beach, with a man claiming that a stray electrical arc from a surgical robot burned his wife’s small intestine during a colon cancer procedure, causing her death. The article quotes Intuitive Surgical’s 2023 financial report, which notes 8 606 da Vinci systems in use worldwide, having performed 2 286 000 procedures in 2023. The financial report mentions an undisclosed number of pending lawsuits, which the company disputes.
Nevertheless, Forgan remains an advocate.
Exiting via Tygerberg’s maze of corridors, he continues to reflect on his job. After our meeting, he is set to deliver a talk at the Cape Town International Convention Centre. His manner is earnest. Shrugging, he describes himself as a “glorified plumber”.
Research by West Virginia University has demonstrated that American Heart Association and American Stroke Association guidelines are effective at speeding up hospitals’ response times for stroke treatment and can be mastered even by members of ‘ad hoc‘ medical teams that assemble rapidly on the fly.
When a stroke patient arrives at an emergency room, specialists from across hospital departments – emergency medical services, neurologists, pharmacists, physicians, nurses, radiologists and technicians – rush to coordinate a team response. AHA and ASA guidelines put specific limits on how much time can optimally elapse between the onset of ischaemic stroke, in which blood flow to the brain is blocked, and subsequent events like arrival at the hospital and delivery of an infusion.
But experts have questioned whether the communication of those best practices helps medical teams that assemble temporarily and whose members don’t typically collaborate. In a Journal of Operations Management article, WVU associate professor Bernardo Quiroga and coauthors answer that question using data about more than 8000 patients who received stroke care at a large hospital between 2009 and 2017.
“‘Time is brain’ for stroke victims,” Quiroga explained. “Blocked blood flow to the brain kills almost two million neurons a minute, so your life or ability to walk or talk hinges on how quickly multiple professionals coordinate to restore blood flow. If you’re lucky, you’re treated within the first hour of symptom onset. Better yet, you receive a shot of Tissue Plasminogen Activator, which dissolves clots. TPA works better the earlier it’s given and usually isn’t effective after 4.5 hours.”
In 2010, the AHA and ASA launched Target: Stroke, a program that identifies stroke care best practices and standardises each step in the process. Participating hospitals reduced median treatment times from 79 minutes in 2009 to 51 minutes in 2017, but it wasn’t clear if that improvement was driven by adherence to best practices or by clinicians learning through repetition as they handled more stroke cases.
To figure that out, the researchers investigated whether repeated ‘learning by doing’ decreased the hospital’s stroke care time. Then, they evaluated whether deliberate, ‘induced’ learning and implementation of AHA/ASA best practices decreased the time further.
Learning through repetition worked. The more strokes the hospital treated, the faster it responded. For each doubling of cumulative stroke alerts, ‘door-to-needle time’ – the time to get patients from the hospital door to a TPA infusion – decreased by 10.2%.
Best practices also worked. Specifically, the researchers examined two best practices: the Helsinki Model protocol, which directs that EMS staff keep stroke patients on the stretcher for transport to the CT room rather than transferring them to ER beds; and the Rapid Administration of TPA protocol, which requires the pharmacist to be in the CT room with TPA before completion of the CT scan. Those protocols significantly reduced the hospital’s door-to-needle time beyond improvements from repetition-based learning.
According to Quiroga’s coauthor and former PhD student Brandon Lee, that matters because it demonstrates the efficacy of best practices and shows ad hoc teams learning guidelines and implementing them long-term.
However, Lee emphasised the importance of the presence of the hospital’s stroke advisory committee, which set targets, evaluated stroke teams’ performances and gave feedback.
Without similar “countermeasures to organisational forgetting,” Quiroga acknowledged that best practices aren’t always sustainable, especially on ad hoc teams.
“In the case of the best practice indicated by the Helsinki Model, compliance is difficult because the hospital needs to coordinate with multiple independent EMS systems. Some EMS providers may be reluctant to commit resources to extended time in the CT room, and EMS staff turnover may lead to forgetting,” Quiroga said.
Lee added, “Overall, because ad hoc teams are fluid, information sharing is harder. And when a group of people don’t know each other well, group learning slows. But although ad hoc teams learn more slowly, we determined they still learn.”
The research also assessed whether neurologists’ abilities to meet time goals were affected by their recent experiences treating prior stroke patients.
“As team leaders, neurologists can have an outsized influence on performance,” Quiroga said. “Because other members of the ad hoc team aren’t familiar with each other, they lean on their leader.”
But data showed stroke teams improving response times regardless of how many stroke cases the neurologist had treated individually or what the neurologist’s recent success rate was. Quiroga said that’s good news.
“The implication is that learning and sustaining best practices ensures an even quality of care for patients, regardless of individual neurologists’ experience levels.”
The current method for assessing medication-related liver injury does not accurately reflect some medications’ toxicity to the liver, according to a new study led by University of Pennsylvania researchers. Hepatotoxicity classification has historically been determined by counting individual reported cases of acute liver injury (ALI). Instead, the researchers used real-world health care data to measure rates of ALI within a population and uncovered that some medications’ levels of danger to the liver are being misclassified. Their paper was published in JAMA Internal Medicine.
“From a clinical standpoint, knowing the rate of severe ALI after starting a medication in real-world data will help determine which patients should be monitored more closely with liver-related laboratory tests during treatment,” said senior author Vincent Lo Re, MD, MSCE, an associate professor of Medicine and Epidemiology. “Incidence rates of severe ALI can be a valuable tool for determining a medication’s toxicity to the liver and when patients should be monitored, since incidence rates provide a truer, real-world look at this toxicity. Case reports did not accurately reflect observed rates of ALI because they do not consider the number of persons exposed to a medication, and cases of drug-induced liver injury are often underreported.”
Within the study, 17 different medications had rates that exceeded five severe ALI events per 10 000 person-years. The team determined that 11 of these medications were in lower categories of hepatoxicity by case counts that were likely not reflective of their true risk, since their incidence rates revealed higher levels of toxicity. One of the medications that fell into this group was metronidazole, an antimicrobial that can be used to treat infections in the reproductive or gastrointestinal systems, as well as some dermatological conditions.
Incidence rates, the number of new cases of a disease within a time period divided by the number of people at risk for the disease, are a key measure for examining health in a population because they give a more complete picture than simple counting. For instance, a medication with 60 reports of liver injury would be considered the most hepatotoxic through the traditional method, using the raw number of reported liver injury cases. However, if that medication had 60 observed severe ALI events and was used by five million people, the incidence rate would be very low and likely point to the medication not being dangerous to the liver. However, if 60 severe ALI events were observed within a population of 1,000 patients, it would reflect a higher, potentially more important, rate of injury.
To determine incidence rates, Lo Re and his team, including lead author Jessie Torgersen, MD, MHS, MSCE, an assistant professor of Medicine, examined electronic medical record data on almost 8 million people provided by the United States Veterans Health Administration that had been compiled from 2000 through 2021. Each person did not have pre-existing liver or biliary disease when they began taking any of the 194 medications that were studied. Each of those medications were analysed due to suspicion that they could cause harm to the liver, since each had more than four published reports of liver toxicity associated with their use.
On the other side of the hepatotoxicity coin, the researchers found eight medications that were classified as the most hepatotoxic based on the number of published case reports, but should actually be in the least liver-toxic group, with incidence rates of less than one severe ALI event per 10 000 person-years. For example, rates of severe ALI for statin medications, often used for high cholesterol, were in the group that had fewer than one event per 10 000 person-years.
“The systematic approach that we developed enables successful measurement of the rates of liver toxicity after starting a medication,” Lo Re said. “It wasn’t surprising that the case report counts did not accurately reflect observed rates of severe acute liver injury given the inherent limitations with case reports.”
With these findings, the researchers hope that there might soon be mechanisms established within electronic medical records to alert clinicians to closely monitor the liver-related laboratory tests of patients who start a medication with a high observed rate of severe ALI.
“Importantly, our approach offers a method to allow regulatory agencies and the pharmaceutical industry to systematically investigate reports of drug-induced ALI in large populations,” Lo Re said.
Researchers have developed a simpler and more effective screening method for cervical cancer than the method used today. A comprehensive study published in Nature Medicine shows that the test detects significantly more cancers and precancerous stages.
Most countries have a very extensive cervical cancer screening program that starts with testing for different variants of the human papillomavirus (HPV) that causes cervical cancer. In the case of an HPV-positive test, this is followed by cytological analysis, the examination of gynaecological cell samples by microscopy, which is dependent on human interpretation.
The new molecular test WID-qCIN, which could replace the cytological analysis, can automatically analyse epigenetic changes in cells. These changes, where genes are switched on or off, are influenced by factors such as environment, lifestyle, and aging, and can increase the risk of cancer and other diseases.
Fewer invasive procedures
The current study by researchers at Karolinska Institutet and the University of Innsbruck included more than 28 000 women over the age of 30 who underwent screening in Stockholm between January and March 2017. The researchers analysed a total of 2377 HPV-positive samples with the WID-qCIN test combined with a test for two high-risk HPV types (HPV 16 and 18). In this way, they were able to detect 100% of all invasive cervical cancer and 93% of all serious precancerous lesions that occurred within a year of sampling.
In addition, the new test, in combination with the HPV 16/18 test, was able to predict 69% of all cancers and precancerous lesions up to six years after the sample was taken. This can be compared with only 18% with today’s screening method.
“By integrating the WID-qCIN test into our screening programs, we would be able to identify more cancer cases while reducing the need for invasive procedures,” says Joakim Dillner, Professor of Infectious Disease Epidemiology at Karolinska Institutet and co-author of the study.
A significant improvement
When cell changes are detected in today’s screening program, the woman undergoes a vaginal examination, a so-called colposcopy, where the gynaecologist looks at the cervix with the help of a microscope and, if necessary, takes a biopsy. The biopsy involves a surgical procedure that, among other things, can lead to negative pregnancy outcomes like premature delivery. The results of the current study suggest that implementation of the WID-qCIN test could reduce the number of colposcopy examinations by 40%.
“This would mean a significant improvement compared to today’s screening methods, which were introduced in the 1960s,” says the study’s last author Martin Widschwendter, Professor at the University of Innsbruck (Austria) and visiting Professor at Karolinska Institutet. “With its simplicity and objective assessment, the WID-qCIN test can improve the effectiveness of these programs and support the global strategy to eliminate cervical cancer.”
Researchers from the Mātai Institute and the Auckland Bioengineering Institute have developed a new metric from measured blood circulation in the brain. The new metric opens up new research avenues for brain conditions, including Alzheimer’s disease and other forms of dementia. The research has been published in the leading research journal Scientific Reports Nature.
Each time the heart beats, it pumps blood through the brain vessels, causing them to expand slightly and then relax. This pulsation in the brain helps distribute blood evenly across different areas of the brain, ensuring that all parts receive the oxygen and nutrients they need to function properly.
In healthy vessels, the pulse wave is dampened before it reaches the smallest vessels, where high pulsatility could be harmful. The new metric provides a comprehensive measure of the small vessel pulsatility risk.
The new metric is based on 4D flow MRI technology, and is particularly crucial because increased vascular pulsatility is linked to several brain conditions, including Alzheimer’s disease and other forms of dementia.
By accurately measuring how pulsatility is transmitted in the brain, researchers can better understand the underlying mechanisms of these diseases and potentially guide the development of new treatments.
Current MRI methods face limitations due to anatomical variations and measurement constraints. The new technique removes this issue by integrating thousands of measurements across all brain vessels, rather than the traditional method of looking at one spot. This provides a richer metric representative of the entire brain.
“The ability to measure how pulsatility is transmitted through the brain’s arteries could revolutionise our approach to neurological diseases, and support research in vascular damage hypotheses,” says first author Sergio Dempsey.
“Our method allows for a detailed assessment of the brain’s vascular health, which is often compromised in neurodegenerative disorders.”
The study also highlighted the potential to enhance clinical assessments and research on brain health. By integrating this new metric into routine diagnostic procedures, healthcare providers can offer more precise and personalised care plans for individuals at risk of or suffering from cognitive impairments.
To make the most of the new metric’s implications for patient care, the researchers have made their tools publicly available, integrating them into pre-existing open-source software. This enables scientists and clinicians worldwide to adopt the advanced methodology, fostering further research and collaboration in the field of neurology.
Results from the initial study of the metric also identified important sex differences in vascular dynamics which has initiated a new study focusing on sex-related dynamics.
The research team is planning further studies to explore the applications of this technique in larger and more diverse populations.
In 2018, Arthur Ashkin won the Nobel Prize in Physics for inventing optical tweezers: laser beams that can be used to manipulate microscopic particles. While useful for many biological applications, optical tweezers require extremely controlled, static conditions to work properly.
“Optical tweezers work by creating a light ‘hotspot’ to trap particles, like a ball falling into a hole. But if there are other objects in the vicinity, this hole is difficult to create and move around,” says Romain Fleury, head of the Laboratory of Wave Engineering in EPFL’s School of Engineering.
Fleury and postdoctoral researchers Bakhtiyar Orazbayev and Matthieu Malléjac have spent the last four years trying to move objects in uncontrolled, dynamic environments using soundwaves. In fact, the team’s method – wave momentum shaping – is entirely indifferent to an object’s environment or even its physical properties. All the information that’s required is the object’s position, and the soundwaves do the rest.
“In our experiments, instead of trapping objects, we gently pushed them around, as you might guide a puck with a hockey stick,” Fleury explains.
The unconventional method, funded by the Swiss National Science Foundation (SNSF) Spark program, has been published in Nature Physics in collaboration with researchers from the University of Bordeaux in France, Nazarbayev University in Kazakhstan, and the Vienna University of Technology in Austria.
Very simple, very promising
If soundwaves are the hockey stick in Fleury’s analogy, then a floating object like a ping-pong ball is the puck. In the lab’s experiments, the ball was floating on the surface of a large tank of water, and its position was captured by an overhead camera. Audible soundwaves emitted from a speaker array at either end of the tank directed the ball along a pre-determined path, while a second array of microphones ‘listened’ to the feedback, called a scattering matrix, as it bounced off of the moving ball. This scattering matrix, combined with the camera’s positional data, allowed the researchers to calculate in real time the optimal momentum of the soundwaves as they nudged the ball along its path.
“The method is rooted in momentum conservation, which makes it extremely simple and general, and that’s why it’s so promising,” Fleury says.
He adds that wave momentum shaping is inspired by the optical technique of wavefront shaping, which is used to focus scattered light, but this is the first application of the concept to moving an object. What’s more, the team’s method is not limited to moving spherical objects along a path: they also used it to control rotations, and to move more complex floaters like an origami lotus.
Mimicking conditions inside the body
Once the scientists succeeded in guiding a ping-pong ball, they performed additional experiments with both stationary and moving obstacles designed to add inhomogeneity to the system. Successfully navigating the ball around these scattering objects demonstrated that wave momentum shaping could perform well even in dynamic, uncontrolled environments like a human body. Fleury adds that sound is a particularly promising tool for biomedical applications, as it is harmless and noninvasive.
“Some drug delivery methods already use soundwaves to release encapsulated drugs, so this technique is especially attractive for pushing a drug directly toward tumour cells, for example.”
In a new article published in Nature Reviews Endocrinology, researchers at the University of Illinois Chicago debunk four common myths about the safety of intermittent fasting.
Intermittent fasting as a weight loss method has grown increasingly popular, with a large body of research demonstrating its safety. Despite this, several myths about fasting have spread among clinicians, journalists and the general public: that fasting can lead to a poor diet or loss of lean muscle mass, cause eating disorders, or decrease sex hormones.
In a new commentary, UIC researchers debunk each of these. They base their conclusions on clinical studies, some of which they conducted and some done by others.
“I’ve been studying intermittent fasting for 20 years, and I’m constantly asked if the diets are safe,” said lead author Krista Varady, professor of kinesiology and nutrition at UIC. “There is a lot of misinformation out there. However, those ideas are not based on science; they’re just based on personal opinion.”
There are two main types of intermittent fasting. With alternate-day eating, people alternate between days of eating a very small number of calories and days of eating what they want. With time-restricted eating, people eat what they want during a four- to 10-hour window each day, then don’t eat during the rest of the day. The researchers conclude both types are safe despite the popular myths.
Their conclusions:
Intermittent fasting does not lead to a poor diet: The researchers point to studies showing the intake of sugar, saturated fat, cholesterol, fibre, sodium and caffeine do not change during fasting compared with before a fast. And the percentage of energy consumed in carbohydrates, protein and fat doesn’t change, either.
Intermittent fasting does not cause eating disorders: None of the studies show that fasting caused participants to develop an eating disorder. However, all the studies screened out participants who had a history of eating disorders, and the researchers say that those with a history of eating disorders should not try intermittent fasting. They also urge paediatricians to be cautious when monitoring obese adolescents if they start fasting, because this group has a high risk of developing eating disorders.
Intermittent fasting does not cause excessive loss of lean muscle mass: The studies show that people lose the same amount of lean muscle mass whether they’re losing weight by fasting or with a different diet. In both cases, resistance training and increased protein intake can counteract the loss of lean muscle.
Intermittent fasting does not affect sex hormones: Despite concerns about fertility and libido, neither oestrogen, testosterone nor other related hormones are affected by fasting, the researchers said.
A University of Otago-led clinical trial has tested an oral form of ketamine therapy for treatment-resistant depression that has fewer side effects whilst also reducing the risk of abusing the powerful, tightly-regulated anaesthetic.
Working in collaboration with New Zealand’s Douglas Pharmaceuticals, researchers have conducted a trial of ketamine in an extended-release tablet form. The study, published in Nature Medicine, involved 168 adults for whom regular anti-depressant therapy repeatedly failed. They either took a range of oral doses of ketamine or a placebo for 12 weeks.
Professor Paul Glue, Otago’s Hazel Buckland Chair in Psychological Medicine, says the highest dose of ketamine – 180mg – showed significant improvement in depressive symptoms, compared with patients who received placebo.
“Ketamine can be given by injection or nasal spray, but these methods can leave people feeling spaced out, sedated, and increases their blood pressure. This study shows the extended-release ketamine tablets are safe and effective, and overall, tolerability was good, with participants reporting minimal side effects,” he says.
Douglas Pharmaceuticals is now seeking the interest of partners to complete registrational clinical trials and prepare for commercialisation of the tablets.
“We have found there are many people, here in New Zealand and around the world, who have treatment-resistant depression, and who have no or very little chance of accessing ketamine. Because most doses of this tablet formulation can be taken at home, this is potentially a much cheaper and convenient option for these patients compared with weekly clinic visits for ketamine injections or nasal sprays.”
Ketamine has been used legally by doctors in New Zealand since the 1970s for sedation and pain relief, but it has been classified as an illegal drug for recreational use since the 1980s.
Professor Glue says having the drug in a tablet form reduces the risk of abuse as the manufacturing process makes them difficult to manipulate.
