Day: 01/19/2024

New Research Reveals Neanderthals Hunted Giant Elephants

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Recent research reveals that Neanderthals commonly hunted the extinct straight-tusked elephant, challenging previous notions of their social organization and survival strategies

Finds in Eastern Germany indicate that Neanderthals accumulated large quantities of meat and fat, or gathered in bigger groups for the consumption of elephants.

New research conducted by a team consisting of members of Johannes Gutenberg University Mainz (JGU), the Leibniz-Zentrum für Archäologie (LEIZA), also based in Mainz, and Leiden University in the Netherlands has found that Neanderthals extensively hunted the now extinct straight-tusked elephant (Palaeoloxodon antiquus).

The study has recently been published in the journal PNAS. The researchers closely examined the bones of elephants that are approximately 125,000 years old and that were discovered in Gröbern in Saxony-Anhalt and Taubach in Thuringia, Germany, decades ago. They were able to identify cut marks made by stone tools used by the Neanderthals that indicate that the animals must have been hunted before they were extensively butchered.

Pelvic Bone of a Palaeoloxodon antiquus

The pelvic bone of a Palaeoloxodon antiquus found in Gröbern. 

The pelvic bone of a Palaeoloxodon antiquus found in Gröbern. Credit: Lutz Kindler, LEIZA

It was two years ago that the same team during the analysis of bones found at the Neumark-Nord site, in a former lignite mine in Saxony-Anhalt, discovered the very first evidence that Neanderthals actively hunted straight-tusked elephants, the largest terrestrial mammals of the Pleistocene. This study was published in Science Advances in early 2023.

“The results of the more recent examination of the bones from Gröbern and Taubach now show that the hunting of these elephants by Neanderthals was not an isolated phenomenon but must have been a more regular activity,” emphasized Sabine Gaudzinski-Windheuser, Professor of Prehistoric and Protohistoric Archaeology at JGU and Director of the Archaeological Research Center and Museum of Human Behavioral Evolution MONREPOS in Neuwied, an institute run under the aegis of LEIZA. Gaudzinski-Windheuser was extensively involved in the investigation of the bones from Gröbern and Taubach as well as the previous study of the bones from the Neumark-Nord site.

Palaeoloxodon antiquus Pelvic Bone Neanderthal Incisions

Incisions some 5 millimeters in length made by Neanderthals on the Palaeoloxodon antiquus pelvic bone from Gröbern.

Incisions some 5 millimeters in length made by Neanderthals on the Palaeoloxodon antiquus pelvic bone from Gröbern. Credit: Lutz Kindler, LEIZA

The yield of a straight-tusked elephant bull would have been sufficient to cover the daily calorie requirements of 2,500 Neanderthals

Palaeoloxodon antiquus roamed the landscapes of Europe and Western Asia 800,000 to 100,000 years ago. With shoulder heights of up to four meters and body masses of up to 13 tons, the European straight-tusked elephant was the largest land-living animal at the time, significantly larger than today’s African and Asian elephants and even bigger than the extinct woolly mammoth.

“We have estimated that the meat and fat supplied by the body of an adult Palaeoloxodon antiquus bull would have been sufficient to satisfy the daily calorie intake of at least 2,500 adult Neanderthals,” explained Gaudzinski-Windheuser. “This is a significant number because it furnishes us with new insights into the behavior of Neanderthals.”

Dr. Lutz Kindler documenting fragments of Palaeoloxodon antiquus teeth discovered in Taubach. Credit: Wil Roebroeks, Leiden University

So far, for instance, research has generally assumed that Neanderthals gathered in groups of no more than 20 individuals. However, the information now obtained in relation to the systematic exploitation of straight-tusked elephants indicates that Neanderthals must have gathered, at least temporarily, in larger groups or mastered techniques that allowed them to preserve and store large quantities of foodstuffs – or both.

In a follow-up project, the researchers hope to learn more about how Neanderthals hunted these massive elephants and how their hunting activities impacted these and other prey animals as well as their environments.

Bariatric surgery: shortcut to weight loss or last resort?

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Experts stress the need for surgery to improve obesity-related health issues and help patients improve their lives

More than two in five U.S. adults suffer from obesity, an epidemic that continues to trend upward. While bariatric surgery is an extremely effective treatment option, a new national survey by Orlando Health reveals common stigmas that may deter those who qualify for surgery from pursuing the treatment they need. 

“Treatment plans for obesity are tailored to each individual patient based on things like body mass index and existing medical conditions and may include medication, lifestyle changes, counseling and bariatric surgery,” said Andre Teixeira, MD, medical director and bariatric surgeon at Orlando Health Weight Loss and Bariatric Surgery Institute. “By taking this personalized approach, we are extremely successful in reversing health issues caused by obesity, from diabetes to heart disease. But if someone’s decision is affected by those who think they don’t need surgery or that make them feel like a failure if they have surgery, that greatly diminishes their chances of losing weight and maintaining a healthy lifestyle long term.”

Because of the stigma around obesity and bariatric surgery, so many of my patients feel defeated if they can’t lose weight on their ownMuhammad Ghanem

The survey, conducted by Ipsos, found 79% of Americans believe weight loss surgery should only be pursued as a last resort, and 60% agree that bariatric surgery is a shortcut to shedding pounds, something Dr. Teixeira says couldn’t be further from the truth. “Bariatric surgery is by no means an easy way out. If you have the courage to ask for help and commit to doing the hard work of changing your diet and improving your life, you’re a champion in my book.” Dr. Teixeira said. “Surgery is simply a tool to jumpstart that change. After surgery, it is up to the patient to learn how to eat well, implement exercise into their routine and shift their mindset to maintain their health for the rest of their lives.”

Guidelines by the American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) were recently updated for the first time since 1991 to expand access to bariatric surgery, which is less invasive and safer than ever, thanks to advancements in laparoscopic and robotic surgery techniques. Yet only 1% of those who are clinically eligible undergo surgical treatment for obesity. 

The survey also found that 61% of respondents believe exercise and diet should be enough. “Because of the stigma around obesity and bariatric surgery, so many of my patients feel defeated if they can’t lose weight on their own,” said Muhammad Ghanem, MD, a bariatric surgeon at Orlando Health Weight Loss and Bariatric Surgery Institute. “But when I tell them obesity is a disease and that many of its causes are outside of their control, you can see their relief. They often even shed a tear because they’ve struggled with their weight all their lives and finally have some validation.”

That was the case for Maritza Cruz Rivera, 64, who lived with pain and fatigue for years and finally hit a breaking point during a routine visit to her primary care physician. “When they weighed me before my appointment, I looked at the scale and started to cry. There it was: 227,” Cruz Rivera said. “Something triggered in me in that moment to finally do something about my weight and get some help.” 

Upon learning that bariatric surgery was a good option for her, she spoke with friends and family. While many supported her decision to undergo surgery, she also heard a lot of misconceptions. She says it’s best to get the facts from your doctor and make a decision based on what is best for your health. 

Following surgery, Cruz Rivera changed her relationship with food and began prepping healthy salads and soups that she enjoys. A year later, she is at a healthy weight and is living the life she’s always strived to live, riding her bicycle with her grandchildren, going for long walks in her neighborhood and even doing one of her favorite things: dancing. “I haven’t been able to dance like this in 20 years. I didn’t go into this to look like Barbie, I just wanted to live a healthy life with my family, and now I can do that,” Cruz Rivera said. “For anyone struggling with obesity who feels depressed or stuck like I did, don’t bury yourself in that dark hole. Understand and know that there’s always a solution.”

Blood test to identify genetic diseases in unborn babies

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With the simplicity of a blood test, it will be possible in the future to screen pregnant women for serious genetic diseases in their unborn children.

A research team from Odense University Hospital and the University of Southern Denmark has developed an innovative screening test. With a blood sample from the expectant mother, they can scrutinize all the genes in the fetus. In the recently published results of the research project in the New England Journal of Medicine, the researchers analyzed blood samples from 36 pregnant women. The findings indicate that the new test, named desNIPT, has demonstrated effectiveness in identifying alterations in fetal genes – a leading factor in severe congenital diseases. 

When applying the new analytical method, we successfully identified all gene variants responsible for diseases that were previously detected through invasive fetal examinationsIeva Miceikaité

“With our novel approach, we can now screen for the majority of known serious genetic syndromes using a simple blood test from the pregnant woman. Typically, this would otherwise require resorting to chorionic villus sampling or amniocentesis,” states Ieva Miceikaité from the Department of Clinical Research, University of Southern Denmark. “This implies that we now possess enhanced opportunities to pinpoint the genetic cause of developmental issues in the fetus,” she adds. 

At present, the first-generation Non-Invasive Prenatal Test (NIPT) is employed to screen the fetus for prevalent chromosomal disorders, predominantly focusing on conditions such as Down syndrome and a few others resulting from notable chromosomal alterations. “Nevertheless, numerous congenital diseases arise from more subtle modifications in fetal DNA. To identify these, it is essential to examine all genes within the fetal genome,” explains Ieva Miceikaité. 

This screening, referred to as exome sequencing, is presently limited to pregnancies where indications of abnormalities are noted during ultrasound scans. This restriction stems from the fact that the analysis currently necessitates either chorionic villus sampling or amniocentesis, both procedures associated with discomfort and a slight risk of miscarriage. As a result, numerous severe genetic syndromes frequently go undetected until after birth. 

“Our objective was to enhance non-invasive screening options for pregnant women. The new desNIPT test integrates the benefits of NIPT and exome sequencing, delivering comprehensive insights through a more straightforward test,” elucidates Ieva Miceikaité. Alongside her fellow researchers, Ieva Miceikaité monitored 36 pregnant women, analyzing blood samples taken during the 1st or 2nd trimester. In each pregnancy, ultrasound scans had revealed signs indicative of a potential serious genetic disease in the fetus. Out of the 36 pregnancies, newly arising disease-causing alterations in the unborn child were identified in a total of 11 cases. Subsequently, the results from the desNIPT analysis were compared with those from conventional exome sequencing conducted through chorionic villus sampling or amniocentesis. 

“The novel approach to screening pregnant women has been remarkably successful,” states Ieva Miceikaité, further noting: “When applying the new analytical method, we successfully identified all gene variants responsible for diseases that were previously detected through invasive fetal examinations. In this regard, it has demonstrated comparable effectiveness to these invasive procedures.
Promising future for prenatal screening.” 

“The test opens the possibility of screening for many more genetic diseases in the future, including those that cannot be revealed by ultrasound scans,” explains Martin Larsen, leader of the project and associate professor at the Department of Clinical Research, University of Southern Denmark. He envisions significant potential in deploying the test as a screening tool in conjunction with ultrasound examinations – the prevailing standard for all pregnant women – to guarantee a more thorough screening of expectant mothers before childbirth. 

One notable challenge with numerous screening tests is their inconsistent precision, frequently resulting in unwarranted follow-up diagnostic examinations. “We are highly optimistic as the study indicates that the desNIPT test is remarkably accurate. In the examined pregnant women, we did not observe any false-positive results,” states Martin Larsen. 

Since this is a “proof-of-concept” study, the test needs validation in a larger study before it can be made available to pregnant women. “At the outset, our aim was to establish the feasibility of sequencing the fetus’s genes through a blood sample from the pregnant woman. Presently, our focus is on validating the test through a larger study, as well as refining and scaling the methodology,” states Martin Larsen. 

Leukaemia: AI provides support in diagnostics

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AI-based processing of bone-marrow smears to support leukaemia diagnosis. Using...

AI-based processing of bone-marrow smears to support leukaemia diagnosis. Using so-called unsupervised learning methods, single-cell images are extracted from extremely high-resolution image data. Then, using neural networks, these cell images are examined to check for any visual anomalies which might have a genetic origin. Areas which are important for the decision of the neural network are highlighted in colour by using so-called “explainable AI” strategies.

IT specialists and physicians develop new method for recognising genetic aberrations

Decisions on treatment for patients with acute myeloid leukemia (AML) – a highly aggressive form of leukemia – are based, among other things, on a series of certain genetic features of the disease; but at the time when a diagnosis is made, this information is not available. However, evidence of these genetic anomalies is crucial in providing targeted treatment for patients at an early stage. As genetic testing is expensive and time-consuming, there is a great need for inexpensive, fast and broadly accessible tests to predict such anomalies. A team of IT specialists and physicians at the University of Münster and the University Hospital Münster has now published a study showing how a method based on artificial intelligence (AI) can be used to predict various genetic features on the basis of high-resolution microscopic images of bone marrow smears. As a result, decisions on a more precise treatment can be made in future directly on the day of the diagnosis, without the need to wait for genetic analyses. The results have been published in the journal “Blood Advances”.

Interestingly, several patterns recognized by the algorithm can not be identified by human observers. This is for example because the patterns may be too faint or because extremely fine textures are involved which remain hidden to the human eyeBenjamin Risse

In this new method, the genetic aberrations were extracted directly from extremely high-resolution multi-gigabyte scans from whole bone marrow smears taken from more than 400 AML patients. The scans had a resolution of 270,000 times 135,000 pixels on average, with one image being several gigabytes in size. Proceeding from this enormous dataset, it was possible to extract more than two million single-cell images. “We developed a new type of Deep Learning method, fully automatic, which was trained for a complex task by means of machine learning technology,” explains Prof. Benjamin Risse, who headed the work on algorithmic developments on the IT side. “In our case, the basic algorithm can automatically recognise the genetic features and the very fine patterns in big cytological images. The method then filtered the single-cell images into categories of different cell types, and it also showed any genetic aberrations. Interestingly, several patterns recognized by the algorithm can not be identified by human observers. This is for example because the patterns may be too faint or because extremely fine textures are involved which remain hidden to the human eye, despite excellent imaging,” says Risse. 

One key advantage of the method presented is in the end-to-end AI pipeline which enables monitoring of the (interim) results and reduces to a minimum the manual preliminary work often necessary for machine learning. This is made possible by a combination of so-called unsupervised, self-supervised and supervised learning processes. The first two processes require no manual data selection at all but try to extract relevant content automatically from the image data instead. “Using a so-called incremental approach, we carried out intermediary steps with a human expert to examine the images. This is necessary for example in cell images categorised as problematic,” says Dr. Linus Angenendt, who heads the Personalised Cancer Therapy and Digital Medicine working group at Münster University Hospital. Problematic cell images can occur as a result of incorrect staining, for example. The model trained was subsequently evaluated on an independent dataset relating to a further 70 patients with over 440,000 single-cell images – as a test cohort. 

Although the new method cannot replace genetic analyses, it nevertheless helps at a very early stage in the diagnostic clarification process for a leukaemia patient, by providing an idea of which genetic aberrations might underlie the disease. This would be especially helpful in the case of aggressive diseases when there is no time to wait for the complete genetic analyses. 

The researchers are confident that in future digital methods and artificial intelligence will become increasingly important for large medical datasets when it is a question of making personalised recommendations for treatment for patients with malignant diseases. This study contributes an important basis for this, for example in the development of similar approaches for other bone marrow diseases.

New MRI-based method measures tumor malignancy

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The cycling of water across membrane transporters is an hallmark of the cell metabolism and is potentially of high diagnostic significance for the characterization of tumors and other diseases.

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In the journal Angewandte Chemie, an Italian research team has now introduced a new MRI-based method for assessing this water exchange. By this method, they were able to estimate the degree of malignancy and the success of treatments in mice tumor models. 

Not all cancers are equal. Depending on the type of tumor, a given treatment may be spot on or fail completely. For targeted, effective, treatment that is as gentle as possible, it is important to precisely locate the tumor and determine its malignancy. Magnetic resonance imaging (MRI) provides excellent time- and spatially resolved images for the characterization of tumors. During this procedure, the patient lies in a “tube” in which there is a very strong magnetic field. The spins of protons (the nuclei of hydrogen atoms) align themselves in this magnetic field. Radio waves are beamed in and synchronize the precessions of the spins, temporarily flipping some of them. Depending on the composition of the tissue, this “magnetization” is lost at different times (relaxation). This can be used to compute 3D images. Gadolinium contrast agents reduce the relaxation times. These agents are more concentrated in tumors because their blood vessels are particularly permeable. This increases the contrast and makes it easier to define the tumor. 

Contrast agents only spread through the extracellular compartments of the tumor; they do not enter tumor cells. A team led by Giuseppe Ferrauto and Silvio Aime wanted to exploit this feature to determine the degree of water exchange through the cell membrane. Tumor cells are more metabolically active than healthy cells and have more transport proteins and channels in their cell membranes. These proteins also allow water to enter and exit the cell, and the degree of water exchange is a measure of the aggressiveness of a tumor. Yet, classic MRI cannot show this.

Imaging without ionising radiation: MRI uses magnetic fields to look inside the body. Keep up-to-date with the latest research news, medical applications, and background information on MR imaging.

The team from the University of Torino and IRCCS SDN SynLab in Naples decided to work with a new MRI method called CEST (Chemical Exchange Saturation Transfer). There is constant proton exchange between free water and hydrogen-containing groups in biomolecules, such as the amine groups in creatine. The radio frequencies at which a proton can be “magnetized” depends on the chemical environment of that proton, so frequencies are different for protons in free water and those bound to creatine, for example. With a matching pulse, the creatine-bound protons can be saturated. These protons are exchanged and bind to nearby free water. They keep their “saturated magnetization state” as they do this. If radio waves with the right frequency for free water protons are then pulsed, an increasing number of these protons are already magnetized and cannot absorb the energy (the CEST signal in MR images). Absorption decreases until the proton exchange reaches equilibrium. This makes it possible to draw conclusions about the concentration of creatine and other proton exchanging molecules in a cell, which can be used for cancer phenotyping. 

If a contrast agent is then administered and enters the extracellular compartment, the magnetization of the water protons there decreases significantly faster. Because water is exchanged through the membrane, the number of magnetized water protons within the cells also decreases more quickly. This in turn changes the CEST signals. The changes after addition of contrast agent reflect the permeability of the tumor cell membrane to water. 

The team tested this method in mouse models for breast cancer with different degrees of malignancy. As expected, the observable water exchange increase as the tumors grew more aggressive. Within the tumors, it was also possible to differentiate between areas of differing malignancy. The cytostatic drug Doxorubicin immediately reduced the water permeability. Hence, the developed method sheds light into tumor phenotype and provides a new tool to assess the outcome of chemotherapy. 

Placenta organoids help understand pre-eclampsia and pregnancy disorders

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Placental organoid (circle in the centre). Trophoblast cells are invading out...

Placental organoid (circle in the centre). Trophoblast cells are invading out of the organoid, mimicking placental cells invading the uterus in the early weeks of pregnancy.

Scientists have grown ‘mini-placentas’ in the lab and used them to shed light on how the placenta develops and interacts with the inner lining of the womb – findings that could help scientists better understand and, in future, potentially treat pre-eclampsia.

The study, published in Cell Stem Cell, shows that it is possible to experiment on a developing human placenta, rather than merely observe specimens, in order to study major disorders of pregnancy. 

Successful pregnancy depends on the development of the placenta in the first few weeks of gestation. During this period, the placenta implants itself into the endometrium – the mucosal lining of the mother’s uterus. Interactions between the cells of the endometrium and the cells of the placenta are critical to whether a pregnancy is successful. In particular, these interactions are essential to increase the maternal blood supply to the placenta, necessary for fetal growth and development. 

Women usually present with pre-eclampsia at the end of pregnancy, but really to understand it – to predict it and prevent it – we have to look at what’s happening in the first few weeksMargherita Turco

When these interactions do not work properly, they can lead to complications, such as pre-eclampsia, a condition that causes high blood pressure during pregnancy. Pre-eclampsia occurs in around six in 100 first pregnancies and can put at risk the health of both the mother and the baby. 

Professor Ashley Moffett from the Department of Pathology at the University of Cambridge said: “Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study – the period after implantation, when the placenta embeds itself into the endometrium, is often described as a ‘black box of human development’. Over the past few years, many scientists – including several at Cambridge – have developed embryo-like models to help us understand early pre-implantation development. But further development is impeded because we understand so little about the interactions between the placenta and the uterus.” 

Professor Moffett and colleagues at the Friedrich Miescher Institute, Switzerland, and the Wellcome Sanger Institute, Cambridge, have used ‘mini-placentas’ – a cellular model of the early stages of the placenta – to provide a window into early pregnancy and help improve our understanding of reproductive disorders. Known as ‘trophoblast organoids’, these are grown from placenta cells and model the early placenta so closely that they have previously been shown to record a positive response on an over-the-counter pregnancy test. 

In previous work, Professor Moffett and colleagues identified genes that increase the risk of or protect against conditions such as pre-eclampsia. These highlighted the important role of immune cells uniquely found in the uterus, known as ‘uterine natural killer cells’, which cluster in the lining of the womb at the site where the placenta implants. These cells mediate the interactions between the endometrium and the cells of the placenta. 

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“iPlacenta” could transform healthcare in pregnancy

A placenta on a chip developed at the University of Dundee has the potential to transform research into life-threatening conditions in pregnancy.

In their new study, her team applied proteins secreted by the uterine natural killer cells to the trophoblast organoids so that they could mimic the conditions where the placenta implants itself. They identified particular proteins that were crucial to helping the organoids develop. These proteins will contribute to successful implantation, allowing the placenta to invade the uterus and transform the mother’s arteries. “This is the only time that we know of where a normal cell invades and transforms an artery, and these cells are coming from another individual, the baby,” said Professor Moffett, who is also a Fellow at King’s College, Cambridge. “If the cells aren’t able to invade properly, the arteries in the womb don’t open up and so the placenta – and therefore the baby – are starved of nutrients and oxygen. That’s why you get problems later on in pregnancy, when there just isn’t enough blood to feed the baby and it either dies or is very tiny.” 

The researchers also found several genes that regulate blood flow and help with this implantation, which Professor Moffett says provide pointers for future research to better understand pre-eclampsia and similar disorders. 

Dr Margherita Turco, from the Friedrich Miescher Institute in Switzerland and co-lead of this work, added: “Despite affecting millions of women a year worldwide, we still understand very little about pre-eclampsia. Women usually present with pre-eclampsia at the end of pregnancy, but really to understand it – to predict it and prevent it – we have to look at what’s happening in the first few weeks. Using ‘mini-placentas’, we can do just that, providing clues as to how and why pre-eclampsia occurs. This has helped us unpick some of the key processes that we should now focus on far more. It shows the power of basic science in helping us understand our fundamental biology, something that we hope will one day make a major difference to the health of mothers and their babies.” 

Researchers develop contact lenses to diagnose glaucoma

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Glaucoma effects around 70 million people worldwide and can cause irreversible loss of vision if not treated – but around half of those living with the condition are not aware of it.

Usually developing slowly over time, many cases of glaucoma are only picked up during routine eye tests, by which time lasting damage may already have been caused. But this could change in future as academics from the UK and Turkey have developed a contact lens which can detect changes in eye pressure which signal possible glaucoma. 

Glaucoma occurs when the optic nerve, which connects the eye to the brain, becomes damaged, usually by a build-up of fluid in the front part of the eye which increases pressure inside the eye – known as intra-ocular pressure (IOP). The new contact lenses contain micro-sensors which monitor changes in IOP over a period of several hours, sending the data collected wirelessly so it can be analysed by an ophthalmologist and a diagnosis given. 

The research has been carried out by Professor Hamdi Torun, of Northumbria University; and Professors Günhan Dündar and Arda D. Yalcinkaya, of Boğaziçi University, in Istanbul, and has been published in Contact Lens and Anterior Eye, the official Journal of the British Contact Lens Association. Their paper, entitled A first-in-human pilot study of a novel electrically-passive metamaterial-inspired resonator-based ocular sensor embedded contact lens monitoring intraocular pressure fluctuations, sets out the findings from their initial pilot study of six participants.

Having determined that the technology works successfully, they now plan to carry out a further study with a larger group of participants, which will take place over the next year. The lenses will then be made commercially available through their spin-off company GlakoLens. One of the benefits of using the GlakoLens contact lenses to diagnose glaucoma instead of carrying out a traditional examination is that measurements can be taken more easily over a longer period of time, giving a more accurate diagnosis. 

As Professor Torun explains: “Intra-ocular pressure, or IOP, can vary greatly over a 24-hour period, so it is important to monitor the patient either at intervals or ideally continuously for a whole day to get the best insight into the health of their eyes. Traditional methods for measuring IOP involve initially going to a clinic for a single measurement in a day, the result of which can be misleading due to the natural variation of IOP. 

“If a variation is detected, further investigation is then needed which requires hospitalisation for a whole day, during which repeated measurements are taken using a technique called Goldmann applanation tonometry, which involves numbing the eye with drops and then using a small cone to touch the cornea to measure the pressure. However, studies have shown that waking patients up at night to carry out measurements can make the results less accurate, in addition to obvious discomfort to the patients and the economic cost to the healthcare system. The benefit of the contact lenses we have developed is that once placed in the eye, the patient can then go about their day as normal while their IOP measurements are recorded and sent to a doctor for analysis once the 24-hour period of testing is complete.” 

The new system has been tested with six healthy volunteers, during which time they were asked to drink 1.5 litres of water and lie flat to intentionally increase their IOP levels.

While this is not the first time contact lenses have been developed to measure IOP, previous products have used an electrically active silicon chip, which results in a thicker, less comfortable lens. The chip also makes the lens less flexible and can restrict vision, making it more difficult to carry out daily activities. 

The GlakoLens contact lenses use an electrically passive sensor embedded in a disposable soft contact lens, and a wearable electronic readout system to collect, store and process the data – making the lens more comfortable and allowing the patient to go about their day as normal. As well as diagnosing glaucoma, there is also potential for the lenses to be used to detect other health conditions by measuring glucose, lactic acid and other molecules present in eye. As Professor Torun adds: “We believe this technology has huge potential and could not only save the sight of patients in the early stages of glaucoma but also provide early diagnosis of other diseases in future.”

Does the ‘obesity paradox’ exist? New research debunks myth.

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New research has debunked the idea that there is an “obesity paradox”, whereby patients with heart failure who are overweight or obese are thought to be less likely to end up in hospital or die than people of normal weight.

The study, which is published in the European Heart Journal1, shows that if doctors measure the ratio of waist to height of their patients, rather than looking at their body mass index (BMI), the supposed survival advantage for people with a BMI of 25kg/m2 or more disappears. 

The “obesity paradox” relates to counter-intuitive findings suggesting that, although people are at greater risk of developing heart problems if they are overweight or obese, once a person has developed a heart condition, those with higher BMIs appeared to do better and were less likely to die than those of normal weight. Various explanations have been suggested, including the fact that once someone has developed heart problems, some extra fat is somehow protective against further health problems and death, especially as people who develop a severe and chronic illness often lose weight.

John McMurray, Professor of Medical Cardiology at the University of Glasgow (UK), who led the latest research, said: “It has been suggested that living with obesity is a good thing for patients with heart failure and reduced ejection fraction – which is when the main chamber of the heart is unable to squeeze out the normal amounts of blood. We knew this could not be correct and that obesity must be bad rather than good. We reckoned that part of the problem was that BMI was a weak indicator of how much fatty tissue a patient has.” 

As Professor Stephan von Haehling, Consultant Cardiologist, and Dr Ryosuke Sato, a research fellow, both at the University of Göttingen Medical Center (Germany), write in an accompanying editorial2, BMI fails to take account of the body’s composition of fat, muscle and bone, or where the fat is distributed. “Would it be feasible to assume that an American professional wrestler (more muscle) and a Japanese sumo wrestler (more fat) with the same BMI would have a similar risk of cardiovascular disease? The same is true for persons such as Arnold Schwarzenegger in his younger years when he starred as the ‘Terminator’ with a BMI of ~30 kg/m2.” 

The new study is the first to look at different ways of measuring the size and proportions of patients, including BMI, but also anthropometric measurements such as waist-to-height ratio, waist circumference and waist-to-hip ratio, and adjusting the patient outcomes to take account of other factors that play a role in, or predict, these outcomes, such as levels of natriuretic peptides – hormones that are secreted in the blood when the heart is under pressure, as with heart failure. “Natriuretic peptides are the single most important prognostic variable in patients with heart failure. Normally, levels of natriuretic peptides rise in people with heart failure, but patients living with obesity have lower levels than those who are normal weight,” said Prof. McMurray.

The underdiagnosis of heart failure in people living with obesity is a major issue in primary care. Patients’ symptoms of breathlessness are often dismissed as due solely to obesityJohn McMurray

Prof. McMurray and colleagues analysed data from 1832 women and 6567 men with heart failure and reduced ejection fraction who were enrolled in the PARADIGM-HF international randomised controlled trial taking place in 47 countries on six continents.3 When the patients were randomised, doctors collected data on BMI, blood pressure, anthropometric measurements, results from blood tests, medical histories and treatments. The researchers were interested in which patients were hospitalised with heart failure or who died from it. An “obesity-survival paradox” showed lower death rates for people with BMIs of 25 kg/m2 or more4, but this was eliminated when the researchers adjusted the results to take account of all the factors that can affect outcomes, including levels of natriuretic peptides. 

First author of the study, Dr Jawad Butt, a research fellow from Copenhagen University Hospital—Rigshospitalet, Copenhagen (Denmark), who carried out the analyses, said: ”The paradox was far less evident when we looked at waist-to-height ratios, and it disappeared after adjustment for prognostic variables. After adjustment, both BMI and waist-to-height ratio showed that more body fat was associated with a greater risk of death or hospitalisation for heart failure, but this was more evident for waist-to-height ratio. When looking at waist-to-height ratio, we found the top 20% of people with the most fat had a 39% increased risk of being hospitalised for heart failure compared to people in the bottom 20% who had the least fat.” 

Prof. McMurray said: “Our study shows there is no ‘obesity survival paradox’ when we use better ways of measuring body fat. BMI does not take into account the location of fat in the body or its amount relative to muscle or the weight of the skeleton, which may differ according to sex, age and race. In heart failure specifically, retained fluid also contributes to body weight. It is indices that do not include weight, such as waist-to-height ratio, that have clarified the true relationship between body fat and patient outcomes in our study, showing that greater adiposity is actually associated with worse not better outcomes, including high rates of hospitalisation and worse health-related quality of life. 

“Obesity is not good and is bad in patients with heart failure and reduced ejection fraction. These observations raise the question as to whether weight loss might improve outcomes, and we need trials to test this. In the UK, the National Institute for Health and Care Excellence, NICE, now recommends that waist-to-height ratio instead of BMI is used for the general population, and we should support this for patients with heart failure too. It is important because the underdiagnosis of heart failure in people living with obesity is a major issue in primary care. Patients’ symptoms of breathlessness are often dismissed as due solely to obesity. Obesity is a risk factor and driver of heart failure. Whereas in the past weight loss may have been a concern for patients with heart failure and reduced ejection fraction, today it is obesity.” 

“Can we tell obese heart failure patients just to stay as they are?”

Prof. von Haehling and Dr Sato write in their editorial: “The present findings raise the alarm over the term ‘obesity paradox’, which has been claimed to be based on BMI. Can we tell obese HF [heart failure] patients just to stay as they are? To adequately address this question, not only should the obesity paradox be revisited even in patients with HF with preserved ejection fraction (HFpEF) and in lean HF patients by WHtR [waist-to-height ratio], which better reflects pathophysiological processes of obesity, but also further tests are warranted to validate the effect of weight loss in ‘truly’ obese HF patients with a high WHtR.” 

Limitations of the study are that it can be more difficult to accurately measure body shapes, such as waist circumference, especially when the measurements are carried out by different people; there may be further unknown factors that could affect the results; the analysis was carried out on measurements and other data taken at the time participants joined the study and did not take account of any changes in weight or waist circumference during the follow-up period; there were no data on the cardiorespiratory fitness of the participants, which could have an effect on the link between anthropometric measurements and outcomes; and, finally, only 153 patients were underweight, with a BMI of less than 18.5 kg/m2 , and 171 patients with a waist-to-height ratio of less than 0.4 (0.5 is considered a healthy ratio), so the study’s findings cannot be extrapolated to patients with low BMIs or waist-to-hip ratio.

Intervention after heart attack: don’t wait, revasculate

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Thanks to immediate treatment of all coronary arteries, the risk of later heart...

Thanks to immediate treatment of all coronary arteries, the risk of later heart attacks and also the need for repeat surgery can be reduced.

After a heart attack it might be worth it to already treat constrictions in blood vessels not involved in the heart attack right away during the first intervention to treat the heart attack.

 In a large international study, cardiologists at the University Hospital Zurich (USZ) were able to show that this treatment strategy has advantages over a delayed procedure. The result is highly relevant to clinical practice. The team published their findings in the New Englang Journal of Medicine and also presented the study at the recent ESC cardiology congress. 

A heart attack is caused by the acute blockage of a coronary artery. The affected blood vessels are reopened with an immediate minimally invasive intervention is used to supply blood to the cardiac muscles again. Half of these patients also have additional blood vessels not involved in the heart attack that are constricted by plaques. These patients have a higher risk of future cardiovascular events. Studies have also shown that further heart attacks and re-intervention can be prevented by treating constrictions in the vessels not involved in the heart attack instead of generally treating the blood vessel that caused the heart attack. The ideal time to treat these constrictions in the vessels not involved in the heart attack had been unclear previously.

For the first time, we were able to show that the immediate treatment of all coronary arteries lowers the risk of later heart attacks and also the need for re-interventionBarbara Stähli

In their study, the researchers led by Barbara Stähli, Senior Attending Physician at the USZ Clinic for Cardiology, investigated whether the treatment of constrictions in blood vessels not involved in heart attacks immediately after the re-opening of the vessel causing the heart attack is not inferior to an elective treatment in a secondary procedure. A total of 840 patients with heart attacks and multi-vessel coronary artery disease were studied in the trial at 37 hospitals throughout Europe. The patients were randomly assigned to two groups: In one group, the treatment of the constrictions in blood vessels not involved in heart attacks were treated immediately, and in the other group in a planned second procedure 19 to 45 days later. The study analyzed whether one of the following events occurred after one year: death, another heart attack, stroke, another unplanned ischemia-related intervention or hospitalization due to heart failure. 

The study showed that this was the case in 35 patients (8.5%) in the group that was immediately treated, and in 68 patients (16.3%) in the group in which a delayed treatment was performed. Two results were especially notable: Only eight patients (2%) from the first group suffered another heart attack, whereas 22 (5.3%) did in the second group. Another unplanned ischemia-related intervention was necessary in 17 patients (4.1%) from the first group, and in 39 (9.3%) from the second group. No difference was observed between the two groups in terms of the number of deaths or the number of strokes and hospitalizations due to heart failure. For Barbara Stähli, this was an impressive result: “For the first time, we were able to show that the immediate treatment of all coronary arteries lowers the risk of later heart attacks and also the need for re-intervention.” 

These study results are highly relevant for clinical practice because they show that an immediate intervention does not have any disadvantages for the patients. On the contrary: A strategy of immediate treatment leads to a lower rate of repeat heart attacks and new, unplanned interventions, and at the same time the patient is spared a second planned procedure and re-hospitalization. The study is ultimately of financial interest as well. 

Breast cancer: In-bra ultrasound scanner to improve early detection.

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upper body photo of woman wearing wearable device for breast cancer detection

In hopes of improving the survival rate for breast cancer patients, MIT researchers designed a wearable ultrasound device that could allow women to detect tumors when they are still in early stages.

The new device could allow more frequent monitoring of patients at high risk for breast cancer.

When breast cancer is diagnosed in the earliest stages, the survival rate is nearly 100%. However, for tumors detected in later stages, that rate drops to around 25%. In hopes of improving the overall survival rate for breast cancer patients, Researchers at the Massachusetts Institute of Technology (MIT) have designed a wearable ultrasound device that could allow people to detect tumors when they are still in early stages. In particular, it could be valuable for patients at high risk of developing breast cancer in between routine mammograms. 

The device is a flexible patch that can be attached to a bra, allowing the wearer to move an ultrasound tracker along the patch and image the breast tissue from different angles. In the new study, the researchers showed that they could obtain ultrasound images with resolution comparable to that of the ultrasound probes used in medical imaging centers. “We changed the form factor of the ultrasound technology so that it can be used in your home. It’s portable and easy to use, and provides real-time, user-friendly monitoring of breast tissue,” says Canan Dagdeviren, an associate professor in MIT’s Media Lab and the senior author of the study. 

MIT graduate student Wenya Du, Research Scientist Lin Zhang, Emma Suh, and Dabin Lin, a professor at Xi’an Technological University, are the lead authors of the paper, which appears in Science Advances.

A close-up of the tracker shows that it is Y-shaped and has 3 metallic discs. The tracker is at the end of a yellow strip-cable.

Image credit: Canan Dagdeviren/MIT

For this project, Dagdeviren drew inspiration from her late aunt, Fatma Caliskanoglu, who was diagnosed with late-stage breast cancer at age 49, despite having regular cancer screens, and passed away six months later. At her aunt’s bedside, Dagdeviren, then a postdoc at MIT, drew up a rough schematic of a diagnostic device that could be incorporated into a bra and would allow for more frequent screening of women at high risk for breast cancer. 

My goal is to target the people who are most likely to develop interval cancer. With more frequent screening, our goal to increase the survival rate to up to 98%Canan Dagdeviren

Breast tumors that develop in between regularly scheduled mammograms — known as interval cancers — account for 20-30% of all breast cancer cases, and these tumors tend to be more aggressive than those found during routine scans. “My goal is to target the people who are most likely to develop interval cancer,” says Dagdeviren, whose research group specializes in developing wearable electronic devices that conform to the body. “With more frequent screening, our goal to increase the survival rate to up to 98%.”

To make her vision of a diagnostic bra a reality, Dagdeviren designed a miniaturized ultrasound scanner that could allow the user to perform imaging at any time. This scanner is based on the same kind of ultrasound technology used in medical imaging centers, but incorporates a novel piezoelectric material that allowed the researchers to miniaturize the ultrasound scanner. 

To make the device wearable, the researchers designed a flexible, 3D-printed patch, which has honeycomb-like openings. Using magnets, this patch can be attached to a bra that has openings that allow the ultrasound scanner to contact the skin. The ultrasound scanner fits inside a small tracker that can be moved to six different positions, allowing the entire breast to be imaged. The scanner can also be rotated to take images from different angles, and does not require any special expertise to operate. 

“This technology provides a fundamental capability in the detection and early diagnosis of breast cancer, which is key to a positive outcome,” says Anantha Chandrakasan, dean of MIT’s School of Engineering, the Vannevar Bush Professor of Electrical Engineering and Computer Science, and one of the authors of the study. “This work will significantly advance ultrasound research and medical device designs, leveraging advances in materials, low-power circuits, AI algorithms, and biomedical systems.”

On the left, a yellow strip-cable has a green circuit board on one end, and a...

On the left, a yellow strip-cable has a green circuit board on one end, and a small ultrasound tracker on the other. On the right, the white device is teardrop shaped and has a hexagonal grid of holes where the tracker can be placed.

Image credit: Canan Dagdeviren/MIT 

Working with the MIT Center for Clinical and Translational Research, the researchers tested their device on one human subject, a 71-year-old woman with a history of breast cysts. Using the new device, the researchers were able to detect the cysts, which were as small as 0.3 centimeters in diameter — the size of early-stage tumors. They also showed that the device achieved resolution comparable to that of traditional ultrasound, and tissue can be imaged at a depth up to 8 centimeters. “Access to quality and affordable health care is essential for early detection and diagnosis. As a nurse I have witnessed the negative outcomes of a delayed diagnosis. This technology holds the promise of breaking down the many barriers for early breast cancer detection by providing a more reliable, comfortable, and less intimidating diagnostic,” says Catherine Ricciardi, nurse director at MIT’s Center for Clinical and Translational Research and an author of the study.

This conformable ultrasound patch is a highly promising technology as it eliminates the need for women to travel to an imaging centerTolga Ozmen

To see the ultrasound images, the researchers currently have to connect their scanner to the same kind of ultrasound machine used in imaging centers. However, they are now working on a miniaturized version of the imaging system that would be about the size of a smartphone. 

The wearable ultrasound patch can be used over and over, and the researchers envision that it could be used at home by people who are at high risk for breast cancer and could benefit from frequent screening. It could also help diagnose cancer in people who don’t have regular access to screening. “Breast cancer is the most common cancer among women, and it is treatable when detected early,” says Tolga Ozmen, a breast cancer surgeon at Massachusetts General Hospital who is also an author of the study. “One of the main obstacles in imaging and early detection is the commute that the women have to make to an imaging center. This conformable ultrasound patch is a highly promising technology as it eliminates the need for women to travel to an imaging center.” 

The researchers hope to develop a workflow so that once data are gathered from a subject, artificial intelligence can be used to analyze how the images change over time, which could offer more accurate diagnostics than relying on the assessment of a radiologist comparing images taken years apart. They also plan to explore adapting the ultrasound technology to scan other parts of the body.