An international study identified 15 novel biomarkers that are linked to late-onset dementias. These protein biomarkers predict cognitive decline and subsequent increased risk of dementia 20 years before the disease onset.
The proteins identified by the study are involved with immune system dysfunction, blood-brain-barrier dysfunction, vascular pathologies, and central insulin resistance. Six of these proteins can be modified with currently available medications.
“These findings provide novel avenues for further studies to examine whether drugs targeting these proteins could prevent or delay the development of dementia,” explained lead author Joni Lindbohm MD, PhD from the University College London and University of Helsinki.
The study findings have been published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Pathophysiological research on dementia aetiology has focused on amyloid beta and tau proteins, but thus far prevention and treatment trials targeting these biomarkers have been unsuccessful. This has spurred the search for other potential mechanisms that could predispose to dementia. Recent development of scalable platforms has made it possible to analyse a wide range of circulating proteins, which may reveal novel dementia-linked biological processes.
In this study, the researchers analysed proteins with a novel large-scale protein panel from stored blood samples of the British Whitehall II and US Atherosclerosis Risk in Communities (ARIC) study collected 20 years ago. Using a panel of 5000 proteins, the researchers identified proteins in plasma that predicted cognitive decline in 5-yearly screenings and subsequent onset of clinical dementia. The 15 proteins that were identified were predictive of dementia in both the British and US cohorts.
“This new study is the first step in our 5-year Wellcome Trust funded research programme. We will next examine whether the identified proteins have a causal association with dementia, and whether they are likely to be modifiable, and druggable”, said study author Professor Mika Kivimäki, Director of the Whitehall II study at University College London.
The research programme ultimately aims to identify novel drug targets for dementia prevention.
A new study investigated genetic changes that occur in a serious condition affecting scuba divers — ‘the bends’ — and found that inflammatory genes and white blood cell activity are upregulated. The findings could lead to biomarkers that will help doctors to diagnose the condition more precisely.
The bends, more formally known as decompression sickness, is a potentially lethal condition that can affect divers. Symptoms include joint pain, a skin rash, and visual disturbances. In some patients, the condition can be severe, potentially leading to paralysis and death. The bends can also affect people working in submarines, flying in unpressurised aircraft or in spacewalks.
It has been studied for a long time: a 1908 paper correctly hypothesised that it involves bubbles of gas forming in the blood and tissue due to pressure decrease. Yet even after a century the precise mechanisms underlying the condition are not well understood. Animal studies have suggested that inflammatory processes may have a role in decompression sickness, but no-one had studied this in humans.
Nowadays, getting ‘the bends’ is rare as divers have well-established methods to mitigate risk, such as controlled ascents from the depths. Nevertheless, doctors have no means to test for the condition, if they do encounter it, and instead rely on observing symptoms and seeing whether patients respond to hyperbaric oxygen therapy.
To investigate decompression sickness, the researchers sampled the blood of divers who had been diagnosed with decompression sickness and also divers who had completed a dive without it. The blood samples were drawn at two times: within 8 hours of the divers emerging from the water, and 48 hours afterwards, when those divers with decompression sickness had undergone hyperbaric oxygen treatment. RNA sequencing analysis was done to measure gene expression changes in white blood cells.
“We showed that decompression sickness activates genes involved in white blood cell activity, inflammation and the generation of inflammatory proteins called cytokines,” explained Dr Nikolai Pace of the University of Malta, a researcher involved in the study. “Basically, decompression sickness activates some of the most primitive body defense mechanisms that are carried out by certain white blood cells.”
These genetic changes had diminished in samples from 48 hours after the dive, after the patients had been treated with hyperbaric oxygen therapy — an interesting finding. The results provide a first step towards a diagnostic test for decompression sickness, and may also reveal new treatment targets.
“We hope that our findings can aid the development of a blood-based biomarker test for human decompression sickness that can facilitate diagnosis or monitoring of treatment response,” said Prof Ingrid Eftedal of the Norwegian University of Science and Technology, who was also involved in the project. “This will require further evaluation and replication in larger groups of patients.”
Journal information: “Acute effects on the human peripheral blood transcriptome of decompression sickness secondary to scuba diving” Frontiers in Physiology, DOI: 10.3389/fphys.2021.660402
After looking for just one-twentieth of a second, experts in camouflage breaking can accurately detect not only that something is hidden in a scene, but precisely identify the camouflaged target, with great potential in medical diagnostic settings as well for the military.
Medical College of Georgia neuroscientist Dr Jay Hegdé and his colleagues developed a relatively rapid method for training civilian novices to become expert camouflage breakers, a skill that even allowed them to sense that something was amiss even when there was no specific target to identify.
Experienced radiologists also have this intuitive sense, detecting subtle changes in mammograms, sometimes years before there is a detectable lesion. One of the main goals of radiology education is training novices to develop advanced or ‘expert’ search methods to improve their recognition of abnormalities, While artificial intelligence may significantly improve diagnosis, there is also the potential to improve the skills of humans.
The researchers behind the camouflage breaking technique wanted to know if trainees could detect the actual camouflaged target or just sense that something is out of place, an issue that is highly significant in real world circumstances.
They already knew that they could train most nonmilitary individuals with good vision to break camouflage in as little as an hour daily for two weeks, which could benefit the military.
“The potential for rapid training of novices in the camouflage-breaking paradigm is very promising as it highlights the potential for application to a wide variety of detection and localisation tasks,” said Dr Frederick Gregory, programme manager, US Army Combat Capabilities Development Command Army Research Laboratory. “Results in experts highlight an opportunity to extend the training to real world visual search and visualisation problems that would be of prime importance for the Army to solve.“
This sort of enhanced ability to spot something amiss could have great applications in medical diagnosis and in search and rescue situations, to name a few.
For this study, six adult volunteers with normal or corrected-to-normal vision were trained to break camouflage using Hegdé’s deep-learning method, but received no specific training on how to pinpoint the target. Participants viewed digitally synthesised camouflage scenes such as foliage or fruit and each scene had a 50-50 chance of containing no target versus a camouflaged target like a human head or a novel, 3D digital image. Similar to how computer scientists ‘trained’ self-driving cars, the idea is to get viewers to get to know the lay of the land that is their focus. “If it turns out there is something that doesn’t belong there, you can tell,” he said.
Trainees could then either look at the image for 50 milliseconds or as long as they wanted, then proceed to the next step where they quickly viewed a random field of pixels, that work like a visual palate cleanser, before acknowledging whether the camouflage image contained a target then using a mouse to show where the target was. “You have to work from memory to say where it was,” he notes.
When the participants could look at the image for as long as they wanted, the reported target location was not much different from when they only had 50 milliseconds — which is not a lot of time for their eyes to move around, Dr Hegdé said.
Again, participants had no subsequent training on identifying precisely where the target was. Yet even without that specific training, they could do both equally well. “This was not a given,” Dr Hegdé noted.
In a second experiment with seven different individuals they used a much-abbreviated training process, which basically ensured participants knew which buttons to push when, using a clearly more pronounced ‘pop-out’ target with scenarios like a black O-shaped target among a crowd of black C shapes. Both the longer and shorter viewing times yielded similar results to the more extensively trained camouflage-breakers both in accuracy and reaction time.
Camouflage is used extensively by the military, from deserts to jungles, with the visual texture changing to blend with the natural environment. “You often are recognised by your outline, and you use these patterns to break up your outline, so the person trying to break your camouflage doesn’t know where you leave off and the background begins,” he said. Animals have also used camouflage for millions of years to evade predators, or to sneak up on prey.
Context is another important factor for recognition, he pointed out, giving the example of not recognising a person whose face you have seen several times when you see them in a different setting. His current Army-funded studies aim to further explore the importance of context, and the ramifications of ‘camouflage breaking’ in identifying medical problems.
He noted that even with his training, some people are inherently better at breaking camouflage than others (he is really bad at it, he admitted) and the reason why is a goal for future research.
In the UK, a “game-changer” method to sample cells for the detection of oesophageal cancer is being trialled in a mobile unit.
The cytosponge, a pill containing a sampling sponge, was developed at the and collects cells which are tested at a laboratory. Details on its development were published in The Lancet. In a previous trial with more than 13 000 participants receiving either the cytosponge or usual care from a GP, the odds of detecting oesophageal cancer were ten times higher than with usual care.
It is hoped the test will be much more efficient and quicker than the current detection method, requiring an endoscopy in hospital.
Prof Rebecca Fitzgerald from the University of Cambridge, which developed the test, said it was “really simple and straightforward”.
Early signs of cancer of the oesophagus are often mistaken for heartburn. It is the sixth most common cause of death from cancer worldwide.
A mobile unit will perform the test at GP surgeries at different locations around the UK.
Prof Fitzgerald, who specialises in cancer prevention, said the cytosponge “can diagnose cancer of the oesophagus really early”.
“Usually you would have to go to the hospital and get an endoscopy, with all that entails, and our idea was could you make something that was so simple you could go to a mobile unit or GP surgery,” Prof Fitzgerald said.
“The simplicity is the absolute key of this – we know the power of diagnosis is in the cells you collect.”
She added that due to COVID, “some endoscopy has been completely on hold so you might have to wait months” for the procedure, where a long, thin tube with a camera is sent down the patient’s mouth and throat.
Prof Fitzgerald explained: “You swallow the capsule on a string with water and it will go down to the top of the stomach.
“The capsule will dissolve in five to seven minutes, and as it dissolves out pops a sponge which has been compressed in that capsule. The nurse simply pulls the sponge out with the string and it will collect about a million cells on its way out.
“We put that sponge into a preservative, send it to the laboratory where it is tested to see whether there are Barrett cells or not and whether the cells look like they are turning to pre-cancer. Then we can let the patient know and if there is anything to worry about they can have an endoscopy and treatment.”
The procedure takes about 10 minutes to perform in total.
Some sunscreen products have been found to contain benzene, a known carcinogen. Photo by RF._.studio from Pexels
An online pharmacy company that also conducts independent testing of consumer products has detected benzene in several sunscreen products.
The company, Valisure LLC, has issued a petition to the Food and Drug Administration in the US to enact stricter rules regarding the presence of benzene in sunscreen products.
Benzene is a colourless or light-yellow liquid chemical at room temperature. A widely used chemical, it has been used primarily as a solvent in the chemical and pharmaceutical industries and is a known carcinogen. Trace levels of benzene may be found in cigarette smoke, gasoline, glues, cleaning products, and paint strippers.
The FDA has forbidden the intentional introduction of the chemical into commercial products due to its toxic properties. The agency does, however, allow benzene-containing products to be sold if the product provides a “substantial therapeutic advance”, on the condition that levels in the product are at or below 2% and that the introduction of benzene into the product is unavoidable. Currently the agency has no guidelines regarding benzene levels in sunscreen products.
Over the past several years, Valisure has become a respected name in product testing—they were behind efforts to have the carcinogen NDMA removed from heartburn medications in 2018, and more recently led the effort to recall hand sanitizers that contained benzene. In 2020, they detected NDMA in metformin, leading to widespread product recalls. In this new effort, the company tested 294 unique batches from 69 different companies. They found significant variability from batch to batch, even within a single company. Fourteen lots of sunscreen and after-sun care products from four different brands contained between 2.78 – 6.26 ppm of benzene; 26 lots from eight brands contained detectable benzene between 0.11 – 1.99 ppm; and 38 lots from 17 brands contained detectable benzene at < 0.1 ppm. There was no detection of benzene in an additional 217 batches of sunscreen from 66 different brands through initial analysis of at least one sample. The company also noted that some of the products they tested had levels that were higher than the 2% cap mandated by the FDA. They also noted that since most of the products they tested did not have any detectable amounts of benzene, it clearly is not an unavoidable byproduct of production. The FDA recently discovered that sunscreen chemicals can be readily absorbed through the skin, they added.
Their petition asks the FDA to ban any amount of benzene in sunscreen and after-tanning care products and issue a recall for those that have measurable levels of benzene that have already been sold. They have also published a table [PDF] that lists sunscreens brands with no detectable levels of benzene in them.
French authorities have announced the detection of a variant of SARS-CoV-2 in the northwestern region of Brittany that has escaped detection by standard polymerase chain reaction (PCR) tests.
Real-time PCR tests are considered to be the current gold standard for detection of SARS-CoV-2, and currently take 4-6h to yield a result. PCR tests make millions to billions of copies of a small sample of DNA to create a larger sample for analysis.
Eight carriers of the variant were identified using genomic sequencing among a cluster of 79 cases in the town of Lannion in the Côtes d’Armor on March 13th.
In a statement on Monday, the French health ministry said that according to initial analyses, the new variant did not appear more transmissible or cause more severe disease. However, on Tuesday, authorities said that this variant was able to escape detection in PCR tests is raising concern.
Belgian virologist and interfederal COVID spokesperson Steven Van Gucht clarified the situation, in that about eight individuals presented with standard coronavirus symptoms, “but the tests remained negative.”
The World Health Organization has labelled this new French COVID variant a ‘variant under investigation’ (VUI), of which there are many thousands currently being monitored, as opposed to more serious variants like the South African B.1.351 variant which is more transmissible and is a ‘variant of concern’ (VOC).
However, just because this variant escaped the PCR tests being used in that area does not mean that it necessarily can escape all of them, as laboratories vary in the tests that they perform.
According to Gucht, tests differ in the different parts of the virus they look for, and also test for at least two to three. “Usually, a good test does not depend on detecting one specific part. So, if there is a mutation in one part of the virus, that signal may be lost, but there is usually a second or third signal that will be found,” explained Gucht.
French authorities are setting up systems to monitor the spread of this variant, and are also putting measures in place to contain it.
In the future, images of the retina could warn of a person’s increased risk of stroke and dementia, making it possible to take preventive measures.
These findings come from preliminary research to be presented at the American Stroke Association’s International Stroke Conference 2021.
Retinopathy is damage to the retina from injury or disease, commonly associated with diabetes. People with severe retinopathy are more likely to have a diseased-looking brain on magnetic resonance imaging (MRI). Retinal tissue has the highest consumption of oxygen in the body, and is the most vulnerable to oxidative stress. Most causes of retinopathy involve damage to the retinal and choroidal circulatory systems.
Study Lead Author Michelle P Lin, MD., MPH, Neurologist at Mayo Clinic explained:”The retina is a window to the brain. A retinal photo that shows a magnified look at the back of the eye, including the retina and optic nerve, is cheaper and faster to perform than an MRI, so we’re wondering if it might be a good screening tool to see who could benefit from a referral to a neurologist for a brain MRI.”
In addition to the ophthalmologist’s office, retinal photos could be taken by a smartphone camera or via a smartphone adapter, Lin said.
Researchers explored the association of retinopathy with stroke, dementia, and the risk of death in 5543 adults who had participated in the annual US National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2008. Interviews were conducted with the participants on a number of aspects of their medical history and health behaviours. Additionally, they received a retinal scan photo to look for signs of retinopathy.
Compared with participants not diagnosed with retinopathy, those with retinopathy were more than twice as likely to have had a stroke. They were also nearly 70% more likely to have dementia; and more likely to die within the next 10 years, with increasing severity of retinopathy conferring a higher risk of death. The odds were calculated after adjusting for risk factors such as age, hypertension, diabetes and smoking.
“If you have retinopathy, work closely with your primary care doctor to alter your vascular risk factors and ask to be screened for cognitive impairment. You may be referred to a neurologist for evaluation and possibly a brain MRI,” said Dr Lin, who is also an assistant professor of neurology at the Mayo Clinic College of Medicine.
A skin swab test has been developed for Parkinson’s disease, based on biomarker analysis of sebum, the oils that protect the skin – and it has a surprising inspiration.
Joy Milne, a retired nurse, noticed a “musky” scent on her husband years before he was diagnosed with Parkinson’s disease. A series of tests showed that she could detect the presence of Parkinson’s disease in people with 100% based on smell alone, prompting research which isolated the compounds she was smelling: higher concentrations of hippuric acid, eicosane, and octadecanal.
In order to exploit these biomarkers, researchers developed a mass spectrometry test to pick up their levels in sebum obtained with skin swabs. This has proved to be around 80% accurate.
Prof Perdita Barran said: “We believe that our results are an extremely encouraging step towards tests that could be used to help diagnose and monitor Parkinson’s.
“Not only is the test quick, simple and painless but it should also be extremely cost-effective because it uses existing technology that is already widely available.
“We are now looking to take our findings forwards to refine the test to improve accuracy even further and to take steps towards making this a test that can be used in the NHS and to develop more precise diagnostics and better treatment for this debilitating condition.”
This new test with its high reliability could help the diagnosis of Parkinson’s disease, which can be easily missed, especially in the early stages. Daxa Kalayci, 56, was misdiagnosed several times over four years before finally finding out she had Parkinson’s in 2019.
“I was misdiagnosed with anxiety, stress-related tremors and told that my problems stemmed from going through the menopause,” she said.
“Despite my diagnosis eventually being confirmed… a quick and simple diagnostic test for Parkinson’s would have given me the chance to start my treatment earlier and enjoy life a lot more.
“But instead, I lost so many years not being able to pursue a career as a paramedic or go back to nursing.
“This test could be a game-changer for people living with Parkinson’s and searching for answers, like I was.”
Siemens Healthineers announced on Wednesday that their antigen self-test kit, which uses samples from a nasal swab, has received limited special approval from the Federal Office for Drugs and Medical Devices (BfArM) for self-use by laypeople in Germany. The regular conformity assessment procedure for the standardised ‘CE‘ mark was also initiated for personal use by laypeople.
“With the provision of the COVID-19 antigen rapid test for possible use by laypeople in Germany, we are breaking new ground and are thus continuing to fulfill our social responsibility to support a return to normal social life,” said Bernd Ohnesorge, Head of Europe, Middle East, and Africa Regions, Siemens Healthineers
The practicability of the kit was confirmed by a study in which 50 participants without medical training personally carried out the test by following the instructions for use. The test already has a CE mark for use by specialist groups for taking samples in the nose.
“The CLINITEST COVID-19 Antigen Self-Test offers users a high degree of flexibility in performing the test with very good quality results,” said Christoph Pedain, Head of Point of Care Diagnostics at Siemens Healthineers.
Siemens’ COVID-19 Antigen Self-Test takes 15 minutes to give a result, using samples taken from both nostrils using a swab. The swab is then washed out in a reagent, which detaches a specific protein from the surface of the virus. The resulting liquid is dripped into a recess in the test cassette.
The test liquid migrates into the field of view of the cassette within 15 minutes, becoming visible as a line. The position and number of lines indicate as to whether there is a positive or negative test result, or whether there was a problem, necessitating a repeat of the test.
In the instructions, the tester is shown the steps to achieve a test result, including instructions on how to proceed according to the test result. A negative test result does not exempt the user from any local COVID regulations. Currently, the test kit is also available in the UK.
The UK variant of the SARS-CoV-2 virus, known as B.1.1.7 could affect the accuracy of certain molecular COVID tests, causing increased false negative results, the US Food and Drug Administration (FDA) has warned.
A false negative from the UK variant could happen if the variant’s mutation happened to be in a part of the virus’ genome that was assessed by that test. However, genetic tests that target multiple parts of the virus genome are less likely to be affected by the new variants, the FDA advises.
Although the possibility of false negative results are to be expected from almost all tests, the effect of the COVID variants could impact the ability to properly monitor the disease, as well as complicating diagnosis.
The FDA issued an alerton Friday, saying that they monitor tests which have received an Emergency Use Authorisation (EUA). They highlight three tests as being affected, with potentially less sensitivity to the mutations:
Accula SARS-Cov-2 Test, from Mesa Biotech
TaqPath COVID-19 Combo Kit, from Thermo Fisher Scientific)
Linea COVID-19 Assay Kit, from Applied DNA Sciences
However, the warning for Accula test was a result of “an abundance of caution”, and the latter two assess multiple genetic targets, so they are not likely to be impacted. The FDA issued recommendations for the users of these devices.The FDA’s warning was prompted by computer simulations showing reduced efficacy in certain tests for the virus variant.
In their press release, the FDA did not specifically mention whether any tests may be affected by mutations in the South African virus variant.
