Day: July 1, 2024

Kaiser Permanente and UCSF researchers find new type of blood thinner improves treatment for venous thromboembolism Patients with blood clots who are on blood thinners for more than 6 months have a lower risk of developing a new blood clot if they are treated with direct oral anticoagulants rather than with the drug warfarin, according to a new study led by Kaiser Permanente and UCSF researchers. Alan Go, MD The retrospective study, published in JAMA Network Open, included 18,495 adults diagnosed with a blood clot in their vein — venous thromboembolism — between 2010 and 2018 who were treated with blood thinners for at least six months. The study found that the patients on direct oral anticoagulants, such as dabigatran (Pradaxa) and factor Xa inhibitors (xabans), had a lower risk of developing a new blood clot than patients on the drug warfarin. Risk of hospitalization for hemorrhage or death was the same for patients taking direct oral anticoagulants or warfarin. Blood clots affect between 300,000 to 600,000 people in the U.S. each year. They are typically treated with blood thinners for a period of 3 to 6 months. Current guidelines suggest extending this treatment window for some patients. The direct oral anticoagulants are recommended for the initial treatment phase but less is known about which anticoagulants are preferred for extended treatment. “These findings highlight the value of observational studies among large, diverse, real-world populations to complement evidence from randomized controlled trials of venous thromboembolism prevention strategies in more selected individuals,” said senior author Alan S. Go, MD, a research scientist at the Kaiser Permanente Northern California Division of Research. Read the UCSF press release.

Neural recording across the vessel wall A micro-endovascular probe (yellow) designed for insertion into straight (versus branched) blood vessels is preloaded into a flexible microcatheter (cyan) and selectively injected into the straight vessel by saline flow. (Courtesy: Anqi Zhang, Stanford University) Brain–machine interfaces (BMIs) provide direct electrical communication between the brain and external electronic systems. As such, BMIs offer potential to restore impaired functionality in patients with paralysis or neurological disorders, by using brain activity alone to directly control prostheses or computer programs, for example, or to modulate nerve or muscle function. Improvements in function and performance are needed, however. Today, most conventional BMIs measure neural activity at the brain’s surface, which provides limited spatial resolution. The ability to record single neuron activity from deep-brain regions could dramatically improve future BMI technology. Measurement of single neurons in deep-brain regions is currently achieved by surgically implanting probes into the brain. This is far from ideal, as surgery can damage brain tissue, as well as cause inflammation and scarring, which rapidly degrade device performance. Clearly, there’s a need for a less invasive and longer-lasting approach. Researchers at Stanford University and Harvard University have developed such a device: an ultrasmall and ultra-flexible micro-endovascular (MEV) neural probe that can be that can be implanted into sub-100-µm-scale blood vessels in the brains of rodents without requiring open-skull surgery. Instead, the device uses the brain’s vascular system as a probe delivery route, inserting the MEV probes via flexible microcatheters. First author Anqi Zhang of Stanford University. (Courtesy: Anqi Zhang) After inserting the microcatheter into the targeted vessel, the probes are injected into deeper vasculature by saline flow. The probes advance smoothly within the microcatheter into the vessels and remain extended without buckling. The researchers explain that the device’s mesh-like structure relaxes and unfolds after injection, allowing the electrodes to adhere against the inner vessel walls in a similar manner to the deployment of a vascular stent. Once in place, the probe can record neuronal signals across the blood vessel wall without damaging the brain or vasculature. Anqi Zhang of Stanford University and Charles Lieber, formerly at Harvard University, explain that “the metabolically active central nervous system requires a dense vascular network, so the average neuron is less than 20 µm from the nearest blood vessel. This vasculature thus offers recording probes access to any brain region without damaging the recorded neural circuits.” Measuring individual neurons For their study, reported in Science, the researchers created probes containing sixteen 80 µm-long platinum electrodes, distributed over a length of 1 cm to examine multiple brain regions. They initially tested the ability of the MEV probes to record activity in the brains of anaesthetized rats, reporting well-defined signals across the 16 channels. In vivo recording recording Micro-endovascular probe in the middle cerebral artery of a rat brain. (Courtesy: Anqi Zhang, Stanford University) The team then induced local seizures in the animals by intracortical injection of penicillin to create epilepsy models. The probes accurately recorded bilateral spikes and spike-wave complexes associated with seizure activity following the injection. Simultaneous recording from all 16 channels demonstrated the ability of the MEV probes to locate and track the seizure foci. To study any short-term effects of the MEV probes, the researchers used laser Doppler flowmetry to monitor cerebral blood flow before and immediately after probe injection. They found that probe implantation did not substantially impact cerebral blood flow. Investigation of chronic effects showed that none of the rats experienced any neurologic deficits, the integrity of the blood–brain barrier was well preserved, there was no increase in vessel wall thickness, and no significant immune response. “These observations not only demonstrate the minimal invasiveness of the MEV probes, but also indicate major advantages in chronic electrophysiology recording, as the accumulation of glial scar tissue near the brain electrodes is known to cause electrode failure in clinically relevant chronic settings,” the team explains. The researchers point out that their probes can be selectively implanted into small vessel branches that are not accessible to any existing microcatheters, thus enabling neural recording across vessel walls at single-cell resolution. Zhang tells Physics World that the team plans to improve the probe design and materials to enable better navigation into different vessel branches. In the long term, the researchers hope to use the probes to study the brain and treat brain diseases, and achieve clinical translation for applications in neurology and interventional radiology. Fibre-based probe enables real-time deep-brain imaging Writing in an accompanying commentary in Science, Brian Timko of Tufts University School of Engineering says that this ability to achieve non-invasive, single-neuron recordings is important for studies of deep-brain regions such as the medial temporal lobe, where activity is not spatially clustered and therefore only identifiable at the single-neuron level. He suggests that future studies could answer long-standing questions about how memories are stored and retrieved. Timko notes that these endothelial probes represent a general platform that in the future could be broadened to incorporate localized stimulation devices. Such stimulation elements might also be used to electroporate the blood vessel wall, enabling localized drug delivery across the blood–brain barrier. He envisions that future development of endovascular probes might ultimately form the foundation for machine interfaces throughout the body.

New research shows that Vlad the Impaler may have cried tears of blood. This condition, known as hemolacria, adds another bloody footnote to the legend of the famously brutal monarch. Vlad the Impaler is believed by many to be the inspiration for the character of Count Dracula. Count Dracula is without question the most famous vampire character of all time. Considering his dark and bloody reputation, it’s not a surprise that when people were searching for the inspiration for the character, many landed on a source who was just about as bloody and brutal as it is possible to be—Vlad the Impaler. Vlad Drăculea, or Vlad the Impaler, was a famously ruthless and brutal 15th century monarch who was known for his unrelenting defense of Wallachia, which was located right next to Transylvania. He was especially well known for a favored method of execution: impaling. It’s estimated that he was responsible for something like 80,000 deaths, of which many were impaling. History didn’t give him his moniker for nothing. Related Story But even the most bloodthirsty or rulers had to, well, rule. And it’s from some of the more mundane aspects of this ruling that researchers were able to learn some surprising new things about the physical wellbeing of an alleged vampire-muse in his prime. More From Popular Mechanics play iconThe triangle icon that indicates to play An international team of researchers recently published a study detailing their analysis of three letters known to have been penned by Vlad the Impaler. While not particularly riveting on their own—they were mostly about run-of-the-mill, bureaucratic things like tax collection—they held within them a wealth of data about the famed ruler. If you touch a piece of glass, you’ll often see a fingerprint left behind. Well, the same goes for if you touch a piece of paper, even if you can’t usually see the print. As Vlad the Impaler was writing these letters, his hand was resting on the paper. And researchers were finally able to analyze that “print” without damaging the historical document on which they were preserved. To do this, the team applied a coat of a substance called ethylene-vinyl acetate. They then removed the substance and tested it using mass spectrometry. In that analysis, the researchers were able to identify about 100 human peptides that had been left behind on the paper. Human proteins were also discovered. Related Story The team could then use these peptides and proteins to see what diseases or conditions Vlad the Impaler would have lived with. And they found a surprising number. According to the paper, the medieval ruler likely dealt with some kind of inflammatory disorder of either the respiratory tract, the skin, or both. And strangely appropriately, given the legends surrounding the historical figure, he also may have had hemolacria—a condition that allows blood to mix with the fluid in ones tear ducts, and those tear ducts to thus produce tears of blood. While the researchers acknowledge that it is highly unlikely that Vlad the Impaler was the only person to have touched these documents, and thereby left peptides and proteins behind, they remain confident that as the writer, his biological mark would have been the most prominent—and as such, the conditions uncovered can reliably be assigned to him. Despite all we knew about the bloody nature of the life of Vlad the Impaler, it seems we still had one more secret to uncover. Associate News Editor Jackie is a writer and editor from Pennsylvania. She’s especially fond of writing about space and physics, and loves sharing the weird wonders of the universe with anyone who wants to listen. She is supervised in her home office by her two cats.

A statue of Vlad the Impaler shown next a letter written by him in 1457. Scientists think traces of proteins found on the letter point to the ruler having had a condition that could mean he shed tears of blood. David Greedy/Getty Images; Pittalà MGG. et al, Analytical Chemistry, 2023, DOI: 10.1021/acs.analchem.3c01461/Insider. p” class=”inline-offer pre-churn-offer”> Redeem now Scientists have analyzed letters written by Vlad the Impaler in the 15th century. Traces of protein on the letters suggest he suffered from hemolacria, which causes blood to be present in tears. The condition would likely have added to the ruler’s fearsome reputation. Vlad the Impaler, the fearsome Romanian ruler that inspired the story of Dracula, may have cried actual tears of blood, a new study suggests. Traces of proteins found on letters he wrote in 1457 and 1475 suggest he suffered from respiratory and skin diseases and could have had a condition known as hemolacria, which is when blood gets mixed in with tears. The findings add one more facet to the ruler’s spine-chilling reputation. Vlad III, also known as Vlad Drăculea “the Son of the Dragon,” has been linked to the deaths of more than 80,000 people, many by impaling. He’s widely thought to be the source of bloody European legends that were later connected to the folklore of “vampirism” to create the myth of the blood-sucking ghouls. It’s possible that the condition would have added to the ruler’s fearsome reputation. A picture of the 1475 letter shows where the traces of protein were collected on the manuscript. Pittalá et al. Analytical Chemistry, 2023, DOI: 10.1021/acs.analchem.3c01461 The analysis — published in a peer-reviewed study by chemists Maria Gaetana Giovanna Pittalà and Vincenzo Cunsolo of the University of Catania, Italy, and colleagues — was able to uncover fragments of 16 proteins that were old enough to have been left behind by the Impaler. These suggested he could have suffered from respiratory and skin diseases, as well as a condition called “hemolacria,” which is when blood gets mixed in with tears. A portrait of Vlad the Impaler. Alexandreea Alexandru/Press Association Images “Although proteomics data cannot be considered exhaustive alone, altogether, these identifications might indicate that Dracula ‘cried tears of blood,’ i.e., he suffered from the condition of hemolacria, as reported by some stories,” the authors said in the study. There is no evidence to suggest he was ever thought to be a “vampire” by his contemporaries. The myth of “Dracula” as a vampire was only introduced in 1897 by Irish writer Bram Stoker in his gothic horror book “Dracula.” But European folklore around the 15th to 17th century did have a concept of “vampirism,” which was often associated with death and disease. Stoker was the first to popularise this concept by making the Impaler a blood-sucking monster. It’s not clear what could have caused the hemolacria. There are a wide variety of disorders that can cause blood tears, ranging from blood clotting issues to unusual menstruation. Analysis of the proteins found traces of a bacteria that causes plague, but this disease is not linked to blood tears. The scientists noted that it’s possible the proteins could have been left behind by others who have touched the paper around that time, though they believe this is unlikely. Still, the analysis provides unprecedented insight into this mysterious figure, more than 500 years after his death, the authors said. “To our reckoning, this is the first time such research has been carried out and has helped to bring to the limelight the health status of Vlad Dracula the Impaler,” the authors said in the study. .content-lock-lock .hidden { display: none; }