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Could sound replace pacemakers and insulin pumps?

<p>Imagine a future in which crippling epileptic seizures, faltering hearts and diabetes could all be treated not with scalpels, stitches and syringes, but with sound. Though it may seem the stuff of science fiction, a <a href="https://dx.doi.org/10.1038/s41467-022-28205-y" target="_blank" rel="noreferrer noopener">new study</a> shows that this has solid real-world potential.</p><p><a href="https://sonogenetics.salk.edu/" target="_blank" rel="noreferrer noopener">Sonogenetics</a> – the use of ultrasound to non-invasively manipulate neurons and other cells – is a nascent field of study that remains obscure amongst non-specialists, but if it proves successful it could herald a new era in medicine.</p><p>In the new study published in <em>Nature Communications</em>, researchers from the Salk Institute for Biological Studies in California, US, describe a significant leap forward for the field, documenting their success in engineering mammalian cells to be activated using ultrasound.</p><p>The team say their method, which they used to activate human cells in a dish and brain cells inside living mice, paves the way toward non-invasive versions of deep brain stimulation, pacemakers and insulin pumps.</p><p>“Going wireless is the future for just about everything,” says senior author Dr Sreekanth Chalasani, an associate professor in Salk’s Molecular Neurobiology Laboratory. “We already know that ultrasound is safe, and that it can go through bone, muscle and other tissues, making it the ultimate tool for manipulating cells deep in the body.”</p><p>Chalasani is the mastermind who first established the field of sonogenetics a decade ago.</p><p>He discovered that ultrasound — sound waves beyond the range of human hearing — can be harnessed to control cells. Since sound is a form of mechanical energy, he surmised that if brain cells could be made mechanically sensitive, then they could be modified with ultrasound.</p><p>In 2015 his research group provided the first successful demonstration of the theory, adding a protein to cells of a roundworm, <em>Caenorhabditis elegans</em>, that made them sensitive to low-frequency ultrasound and thus enabled them to be activated at the behest of researchers.</p><p>This was a milestone achievement for the credibility of the field, but Chalasani’s team soon hit a stumbling block. The same protein that was so successful in sensitising roundworm cells produced no discernible effect at all in mammalian cells. While sonically controlling roundworms is undoubtedly cool, without making the leap to mammalian cells, the potential medical revolution would be dead in its tracks.</p><p>Undeterred, Chalasani and his colleagues set out to search for a new protein that would work in mammals.</p><p>Although a few proteins were already known to be ultrasound sensitive, no existing candidates were sensitive at the clinically safe frequency of 7MHz – so this was where the team set their sights.  </p><p>“Our approach was different than previous screens because we set out to look for ultrasound-sensitive channels in a comprehensive way,” says Yusuf Tufail, a former project scientist at Salk and a co-first author of the new paper.</p><p>The screening process took over a year and encompassed nearly 300 candidate proteins which they tested on dishes of a common human research cell line, but at last the team struck gold. TRPA1, a channel protein that lets cells respond to the presence of noxious compounds and activates a wide range of cells in the body, was the winner, responding to the 7MHz ultrasound frequency.</p><p>“We were really surprised,” says co-first author of the paper Marc Duque, a Salk exchange student. “TRPA1 has been well-studied in the literature but hasn’t been described as a classical mechanosensitive protein that you’d expect to respond to ultrasound.”</p><p>To test whether TRPA1 could activate cell types of clinical interest in response to ultrasound, the team used a gene therapy approach to add the genes for human TRPA1 to a specific group of neurons in the brains of living mice. When they then administered ultrasound to the mice, only the neurons with the TRPA1 genes were activated.</p><p>This leap from theory to physical demonstration is a huge step forward for the burgeoning field. Though it is early days, Chalasani believes the next steps are within reach.</p><p>Clinicians treating conditions including Parkinson’s disease and epilepsy currently use deep brain stimulation, which involves surgically implanting electrodes in the brain, to activate certain subsets of neurons. Chalasani says that sonogenetics could one day replace this approach—the next step would be developing a gene therapy delivery method that can cross the blood-brain barrier, something that is already being studied.</p><p>Perhaps sooner, he says, sonogenetics could be used to activate cells in the heart, as a kind of pacemaker that requires no implantation.</p><p>“Gene delivery techniques already exist for getting a new gene – such as TRPA1 – into the human heart. If we can then use an external ultrasound device to activate those cells, that could really revolutionise pacemakers.”</p><p>Though sonogenetics could one day circumvent medications and invasive surgeries, for now the team is sticking with nailing down the fundamentals. Their current focus is on determining exactly how TRPA1 senses ultrasound, which could allow this sensitivity to be tweaked and enhanced.</p><p><img id="cosmos-post-tracker" style="height: 1px!important;width: 1px!important;border: 0!important" src="https://syndication.cosmosmagazine.com/?id=181725&amp;title=Could+sound+replace+pacemakers+and+insulin+pumps%3F" width="1" height="1" data-spai-target="src" data-spai-orig="" data-spai-exclude="nocdn" /></p><div id="contributors"><p><em><a href="https://cosmosmagazine.com/health/sonogenetics-replace-invasive-medical-treatments/" target="_blank" rel="noopener">This article</a> was originally published on <a href="https://cosmosmagazine.com" target="_blank" rel="noopener">Cosmos Magazine</a> and was written by <a href="https://cosmosmagazine.com/contributor/jamie-priest" target="_blank" rel="noopener">Jamie Priest</a>. Jamie Priest is a science journalist at Cosmos. She has a Bachelor of Science in Marine Biology from the University of Adelaide.</em></p><p><em>Image: Getty Images</em></p></div>

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A wireless, dissolving pacemaker

<p>US researchers have developed a wireless, temporary pacemaker that dissolves harmlessly within the body when it’s no longer required.</p> <p>Having previously developed a <a rel="noreferrer noopener" href="https://cosmosmagazine.com/technology/self-powered-pacemaker-works-heartbeat/" target="_blank">self-powered pacemaker</a>that uses heartbeats as energy, the team has become interested in transient electronics, allowing cardiac patients to dodge riskier surgical procedures.</p> <p>“Sometimes patients only need pacemakers temporarily, perhaps after an open-heart surgery, heart attack or drug overdose,” says Rishi Arora, a cardiologist at Northwestern University, US, and co-author on a paper describing the research, <a rel="noreferrer noopener" href="https://dx.doi.org/10.1038/s41587-021-00948-x" target="_blank">published</a> in <em>Nature Biotechnology.</em></p> <p>“After the patient’s heart is stabilised, we can remove the pacemaker. The current standard of care involves inserting a wire, which stays in place for three to seven days. These have potential to become infected or dislodged.”</p> <p>Arora and colleagues addressed this by creating a biodegradable device, around 15 millimetres in length and width, and 0.25 millimetres thick, from a range of materials, including tungsten-coated magnesium, silicon nanomembranes and Candelilla wax. All the components are ‘bioresorbable’ – they can dissolve and be processed harmlessly by the body.</p> <p>The device is powered by an antenna that sits outside the body, using near-field communication protocols (the same technology used for contactless payments), eliminating the need for batteries or wires and making it easier to implant.</p> <p>“The circuitry is implanted directly on the surface of the heart, and we can activate it remotely,” says Arora.</p> <p>“Over a period of weeks, this new type of pacemaker ‘dissolves’ or degrades on its own, thereby avoiding the need for physical removal of the pacemaker electrodes. This is potentially a major victory for post-operative patients.”</p> <p>The thickness and length of the device can be modified to make it last for different periods of time, depending on the patients’ requirements.</p> <p>The researchers have successfully tested the device in mice, rabbits, rats and dogs, as well as human heart tissue.</p> <p>“The transient electronics platform opens an entirely new chapter in medicine and biomedical research,” says Igor Efimov, a researcher at George Washington University, US, and co-author on the paper.</p> <p>“The bioresorbable materials at the foundation of this technology make it possible to create a whole host of diagnostic and therapeutic transient devices for monitoring progression of diseases and therapies, delivering electrical, pharmacological, cell therapies, gene reprogramming and more.”</p> <div> <div id="vjs_video_3" class="video-js vjs-paused vjs-controls-enabled vjs-workinghover vjs-v7 vjs-user-active vjs-layout-medium bc-player-HJH3i8Guf_default bc-player-HJH3i8Guf_default-index-0 vjs-mouse vjs-plugins-ready vjs-player-info vjs-contextmenu vjs-contextmenu-ui vjs-errors not-hover" data-embed="default" data-usage="cms:WordPress:5.8.1:2.2.0:javascript" data-player="HJH3i8Guf" data-account="5483960636001" data-video-id="6261328609001" aria-label="Video Player"><em>Image credit: Shutterstock</em></div> <div class="video-js vjs-paused vjs-controls-enabled vjs-workinghover vjs-v7 vjs-user-active vjs-layout-medium bc-player-HJH3i8Guf_default bc-player-HJH3i8Guf_default-index-0 vjs-mouse vjs-plugins-ready vjs-player-info vjs-contextmenu vjs-contextmenu-ui vjs-errors not-hover" data-embed="default" data-usage="cms:WordPress:5.8.1:2.2.0:javascript" data-player="HJH3i8Guf" data-account="5483960636001" data-video-id="6261328609001" aria-label="Video Player"></div> <em>This article was originally published on <a rel="noopener" href="https://cosmosmagazine.com/health/a-wireless-dissolving-pacemaker/" target="_blank">cosmosmagazine.com</a> and was written by Ellen Phiddian.</em></div>

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What happened when my mother received a pacemaker

<p><em><strong>Robyn Lee is in her 70s and lives with two lovable but naughty cats. She has published a book on seniors behaving badly, entitled Old Age and Villainy, and considers herself an expert on the subject.</strong></em></p> <p>Several years ago, my 97-year-old mother (aka The Matriarch or TM for short) was diagnosed with heart problems. As time progressed, her symptoms worsened to the point where she started having blackouts. These were eventually attributed to postural hypotension, a condition where her heart rate dropped so low, regardless of whether she was sitting or standing, she would lose consciousness. Unfortunately, it also meant being confined to the house just in case she had a blackout and injured herself, which did not sit well with TM at all. </p> <p>"Bloody hell," she grizzled. "We’re (including her third husband… she’s outlived the first two) used to going out for lunch, we visit friends and go to our singing group. I also play bowls twice a week and now I'm stuck at home."</p> <p>TM went on to relate how they were having their customary glass of wine or three one evening and the next thing she knew, she came to, realising The Third was holding her up as she had lost consciousness and started to topple off her chair.</p> <p>"I spilt my wine all down the front of me," she declared much to the horror of my brothers, cousins, and me. </p> <p>"Oh, no! What a waste of wine!" was our first reaction, (we’re a warped lot).</p> <p>Fortunately, according to TM’s cardiologist, these blackouts were easily righted by either stenting or inserting a pacemaker.</p> <p>"Easy peasy," declared one of TM's friends when she was told about TM’s condition.  "I've had a pacemaker and I'm a new woman!"</p> <p>TM duly had the pacemaker inserted, and three days later I rang to see how she was, only to hear her grumbling about feeling so weak and shaky and that she wanted to get out into the garden, go out to lunch, return to playing bowls, etc. Talk about impatient...</p> <p>However, I rang her again about a week later and it was a different story.  As her balance was not good, which was to be expected at her age, she was provided with a wheelie walker so she felt more secure while walking. I asked TM how she liked the wheelie walker, thinking she might be a bit put out having to use one, but...</p> <p>"It's wonderful," she enthused. "I'm charging round all over the place!  I can get out into the garden and go here and there.  Nothing stops me."</p> <p>Lady Lunchalot was back in circulation.  Though I could understand her glee as she had been stuck home for quite a few months because of her little "turns". </p> <p>TM then described what happened before she had the pacemaker inserted, as I hadn't liked to keep her talking for too long during my earlier call.  Apparently, a nurse explained what to expect in theatre and ended by saying TM would have to take her knickers off.  After thinking about this, TM wondered why, when they would be operating on her chest, she’d have to take her knickers off.</p> <p>Once she was wheeled into theatre, the surgeon introduced himself and the other four doctors there and asked TM if she had any questions.  She queried as to why she’d have to take her knickers off.</p> <p> As TM related it, “Five jaws dropped and five pairs of eyes popped before they roared with laughter.  I could feel myself going red...the first time in my life I've blushed!”.</p> <p>The surgeon explained that the nurse was thinking of earlier days but with the procedures they now had in place deal with germs, it's not like it used to be.  He then told her she could keep her knickers on!</p> <p> A few days later, TM was signing the hospital discharge sheet and noticed the cardiologist’s comments that her heart had been almost totally blocked and beating at only 30 beats per minute.  TM only had one question;</p> <p>"Why am I still here?"</p> <p>Her health had been of concern to us all but with the pacemaker inserted, she was back to her old, not quite so vigorous, self but certainly not sitting at home bemoaning her fate.  In fact, about 10 days after the operation she was at her great niece's wedding. </p> <p>One of my brothers was remarrying a few months after that, (after 30 plus years of being on his own) and badly wanted TM to be at his wedding...this was before the pacemaker insertion. </p> <p>The Matriarch originally didn't want to go because she tired very easily and as she said to me,</p> <p>"I don't want to suddenly drop dead during the wedding and spoil everyone's fun." </p> <p>Which was very thoughtful of her, I suppose, that particular scenario hadn’t occurred to us.  Since the pacemaker, however, TM felt so much better and announced she'd be at the wedding with bells on!  She bought a new outfit for the occasion and looked forward to catching up with other family members. </p> <p>Everything went off very well and she had a wonderful time... without spoiling the wedding with her sudden demise.</p> <p><em>Robyn is writing a series on her 97-year-old mother (aka The Matriarch). <a href="http://www.oversixty.com.au/lifestyle/family-pets/2017/04/robyn-lee-on-her-97-year-old-mother/" target="_blank"><strong><span style="text-decoration: underline;">Read part one here.</span></strong></a> </em></p>

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