In Lab Tests, Researchers Halt Arrhythmias With Gentle Beams—Not Harsh Electric Shocks
Using high-tech human heart models and mouse experiments, scientists at Johns Hopkins and Germany’s University of Bonn have shown that beams of light could replace electric shocks in patients reeling from a deadly heart rhythm disorder.
The findings, published online Sept. 12 in the October 2016 edition of The Journal of Clinical Investigation, could pave the way for a new type of implantable defibrillators.
Current devices deliver pulses of electricity that are extremely painful and can damage heart tissue. Light-based treatment, the Johns Hopkins and Bonn researchers say, should provide a safer and gentler remedy for patients at high risk of arrhythmia, an irregular heartbeat that can cause sudden cardiac death within minutes.
This idea springs from advances in the field of optogenetics, in which light-sensitive proteins are embedded in living tissue, enabling the use of light sources to modify electrical activity in cells.
“We are working towards optical defibrillation of the heart, where light will be given to a patient who is experiencing cardiac arrest, and we will be able to restore the normal functioning of the heart in a gentle and painless manner,” said Natalia Trayanova, who supervised the research at Johns Hopkins.
To move the new heart treatment closer to reality, the scientists at the University of Bonn and Johns Hopkins focused on two different types of research.
The Bonn team conducted tests on beating mouse hearts whose cells had been genetically engineered to express proteins that react to light and alter electrical activity within the organ.
When the Bonn researchers triggered ventricular fibrillation in the mouse heart, a light pulse of one second applied to the heart was enough to restore normal rhythm. “This is a very important result,” said Tobias Bruegmann, one of the lead authors of the journal article. “It shows for the first time experimentally that light can be used for defibrillation of cardiac arrhythmia.”
To find out if this technique could help human patients, Trayanova’s team at Johns Hopkins performed an analogous experiment within a detailed computer model of a human heart, one derived from MRI scans taken of a patient who had experienced a heart attack and was now at risk of arrhythmia.
“Our simulations show that a light pulse to the heart could stop the cardiac arrhythmia in this patient,” said Patrick M. Boyle, a Johns Hopkins biomedical engineering research professor who was also a lead author of the journal article.
To do so, however, the method from the University of Bonn had to be tweaked for the human heart by using red light to stimulate the heart cells, instead of the blue light used in mice. Boyle, who is a member of Trayanova’s lab team, explained that the blue light used in the much smaller mouse hearts was not powerful enough to fully penetrate human heart tissue. The red light, which has a longer wavelength, was more effective in the virtual human tests.
“In addition to demonstrating the feasibility of optogenetic defibrillation in a virtual heart of a patient, the simulations revealed the precise ways in which light alters the collective electrical behavior of the cells in the heart to achieve the desired arrhythmia termination,” Trayanova said.
Boyle added that this aspect of the study highlighted the important role that computational modeling can play in guiding and accelerating the development of therapeutic applications for cardiac optogenetics, a technology that is still in its infancy.
Junior Professor Philipp Sasse of the Institute of Physiology I at the University of Bonn, who is corresponding author of the study and supervised the project in Germany, agreed that the promising light treatment will require much more time and research before it can become a commonplace medical procedure.
“The new method is still in the stage of basic research,” Sasse said. “Until implantable optical defibrillators can be developed for the treatment of patients, it will still take at least five to ten years.”
Discovery shows existing drugs can treat virus
A team of researchers from Florida State University, Johns Hopkins University and the National Institutes of Health has found existing drug compounds that can both stop Zika from replicating in the body and from damaging the crucial fetal brain cells that lead to birth defects in newborns.
One of the drugs is already on the market as a treatment for tapeworm.
“We focused on compounds that have the shortest path to clinical use,” said FSU Professor of Biological Science Hengli Tang. “This is a first step toward a therapeutic that can stop transmission of this disease.”
Tang, along with Johns Hopkins Professors Guo-Li Ming and Hongjun Song and National Institutes of Health scientist Wei Zheng identified two different groups of compounds that could potentially be used to treat Zika — one that stops the virus from replicating and the other that stops the virus from killing fetal brain cells, also called neuroprogenitor cells.
One of the identified compounds is the basis for a drug called Nicolsamide, a U.S. Food and Drug Administration approved drug that showed no danger to pregnant women in animal studies. It is commonly used to treat tapeworm.
This could be prescribed by a doctor today, though tests are still needed to determine a specific treatment regimen for the infection.
Their work is outlined in an article published Monday by Nature Medicine.
Though the Zika virus was discovered in 1947, there was little known about how it worked and its potential health implications — especially among pregnant women — until an outbreak occurred in South America last year. In the United States, there have been 529 cases of pregnant women contracting Zika, though most of those are travel related. As of Aug. 24, there have been 42 of locally transmitted cases in Florida.
The virus, among other diseases, can cause microcephaly in fetuses leading them to be born with severe birth defects.
“It’s so dramatic and irreversible,” Tang said. “The probability of Zika-induced microcephaly occurring doesn’t appear to be that high, but when it does, the damage is horrible.”
Researchers around the world have been feverishly working to better understand the disease — which can be transmitted both by mosquito bite and through a sexual partner — and also to develop medical treatments.
Tang, Ming and Song first met in graduate school 20 years ago and got in contact in January because Tang, a virologist, had access to the virus and Ming and Song, neurologists, had cortical stem cells that scientists needed to test.
The group worked at a breakneck pace with researchers from Ming and Song’s lab, traveling back and forth between Baltimore and Tang’s lab in Tallahassee where they had infected the cells with the virus.
In early March, the group was the first team to show that Zika indeed caused cellular phenotypes consistent with microcephaly, a severe birth defect where babies are born with a much smaller head and brain than normal.
They immediately delved into follow-up work and teamed with NIH’s Zheng, an expert on drug compounds, to find potential treatments for the disease.
Researchers screened 6,000 compounds that were either already approved by the FDA or were in the process of a clinical trial because they could be made more quickly available to people infected by Zika.
“It takes years if not decades to develop a new drug,” Song said. “In this sort of global health emergency, we don’t have time. So instead of using new drugs, we chose to screen existing drugs. In this way, we hope to create a therapy much more quickly.”
All of the researchers are continuing the work on the compounds and hope to begin testing the drugs on animals infected with Zika in the near future.
Learn more: FSU research team makes Zika drug breakthrough
Whether or not they aced it in high school, human beings are physics masters when it comes to understanding and predicting how objects in the world will behave. A Johns Hopkins University cognitive scientist has found the source of that intuition, the brain’s “physics engine.”
This engine, which comes alive when people watch physical events unfold, is not in the brain’s vision center, but in a set of regions devoted to planning actions, suggesting the brain performs constant, real-time physics calculations so people are ready to catch, dodge, hoist — any necessary actions on the fly. The findings, which could help design more nimble robots, are set to be published in the journal Proceedings of the National Academy of Sciences.
“We run physics simulations all the time to prepare us for when we need to act in the world,” said lead author Jason Fischer, an assistant professor of psychological and brain sciences in the Krieger School of Arts and Sciences. “It is among the most important aspects of cognition for survival. But there has been almost no work done to identify and study the brain regions involved in this capability.”
Fischer, along with researchers at Massachusetts Institute of Technology, conducted a series of experiments to find the parts of the brain involved in physical inference. First they had 12 subjects look at videos of Jenga-style block towers. While monitoring their brain activity, the team asked the subjects to either guess where the blocks would land should the tower topple, or if the tower had more blue or yellow blocks. Predicting the direction of falling blocks involved physics intuition, while the color question was merely visual.
Next the team had other subjects watch a video of two dots bouncing around a screen. They asked subjects to predict the next direction the dots would head, based either on physics or social reasoning.
The team found that with both the blocks and dots, when subjects attempted to predict physical outcomes, the most responsive brain regions included the premotor cortex and the supplementary motor area – the brain’s action planning areas.
“Our findings suggest that physical intuition and action planning are intimately linked in the brain,” Fischer said. “We believe this might be because infants learn physics models of the world as they hone their motor skills, handling objects to learn how they behave. Also, to reach out and grab something in the right place with the right amount of force, we need real-time physical understanding.”
In the last part of the experiment, the team asked subjects to look at short movie clips — just look, no other instructions — while having their brain activity monitored. Some of the clips had a lot of physics content, others very little. The team found that the more physical content in a clip, the more the key brain regions activated.
“The brain activity reflected the amount of physical content in a movie, even if people weren’t consciously paying attention to it,” Fischer said. This suggests that we are making physical inferences all the time, even when we’re not even thinking about it.”
The findings offer insight into movement disorders such as apraxia, as it’s very possible that people with damage to the motor areas of the brain also have what Fischer calls “a hidden impairment” — trouble making physical judgments.
A better understanding of how the brain runs physics calculations could also enrich robot design. A robot built with a physics model, constantly running almost like a video game, could navigate the world more fluidly.
Fischer’s co-authors are John G. Mikhael, now a student in the Harvard/MIT MD-PhD program; and Joshua B. Tenenbaum and Nancy Kanwisher, both professors at the McGovern Institute for Brain Research and the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology.
As an important step towards graphene integration in silicon photonics, researchers from the Graphene Flagship have published a paper which shows how graphene can provide a simple solution for silicon photodetection in the telecommunication wavelengths.
Published in Nano Letters, this exciting research is a collaboration between the University of Cambridge (UK), The Hebrew University (Israel) and Johns Hopkins University (USA).
The mission of the Graphene Flagship is to translate graphene out of the academic laboratory, through industry and into society. This broad and ambitious aim has been at the forefront of the choices made to direct the Flagship; it focuses on real problem areas where it can make a real difference such as in Optical Communications.
Optical Communications are increasingly important because they have the potential to solve one of the biggest problems of our information age: energy consumption. Almost everything we do in everyday life consumes information and all of this information is powered by energy. If we want more and more information, we need more and more energy. In the near future, the major consumers of data traffic will be machine-to-machine communication and the Internet of Things (IoT).
To enable the IoT and the level of information it requires, current silicon photonics has a problem: it needs ten times more energy than we can provide. So, if we want this new, improved internet age, new technological, power-efficient solutions need to be found. This is why the drive to graphene-based optical communication is so important.
Over the last few years, optical communications have increased their viability over standard metal-based electronic interconnects. The current silicon-based photodetector used in optical communications has a major issue when it comes to detecting data in the near infrared range, which is the range used for telecommunications. The telecom industry has overcome this problem by integrating germanium absorbers with the standard silicon photonic devices. They have been able to make fully functioning devices on chips using this process. However, this process is complex.
In the new paper, graphene is interfaced with silicon on chip to make high responsivity Schottky barrier photodetectors. These graphene-based photodetectors achieve 0.37A/W responsivity at 1.55μm using avalanche multiplication. This high responsivity is comparable to that of the Silicon Germanium detectors currently used in silicon photonics.
Prof. Andrea Ferrari from the Cambridge Graphene Centre, who is also the Science and Technology Officer and the Chair of the Management Panel for the Graphene Flagship stated; “This is a significant result which proves that graphene can compete with the current state of the art by producing devices that can be made more simply, cheaply and work at different wavelengths. Thus paving the way for graphene integrated silicon photonics.”
Research could help more than 200,000 people annually who suffer from nerve injuries or disease
A national team of researchers has developed a first-of-its-kind, 3D-printed guide that helps regrow both the sensory and motor functions of complex nerves after injury. The groundbreaking research has the potential to help more than 200,000 people annually who experience nerve injuries or disease.
Nerve regeneration is a complex process. Because of this complexity, regrowth of nerves after injury or disease is very rare, according to the Mayo Clinic. Nerve damage is often permanent. Advanced 3D printing methods may now be the solution.
In a new study, published today in the journal Advanced Functional Materials, researchers used a combination of 3D imaging and 3D printing techniques to create a custom silicone guide implanted with biochemical cues to help nerve regeneration. The guide’s effectiveness was tested in the lab using rats.
To achieve their results, researchers used a 3D scanner to reverse engineer the structure of a rat’s sciatic nerve. They then used a specialized, custom-built 3D printer to print a guide for regeneration. Incorporated into the guide were 3D-printed chemical cues to promote both motor and sensory nerve regeneration. The guide was then implanted into the rat by surgically grafting it to the cut ends of the nerve. Within about 10 to 12 weeks, the rat’s ability to walk again was improved.
“This represents an important proof of concept of the 3D printing of custom nerve guides for the regeneration of complex nerve injuries,” said University of Minnesota mechanical engineering professor Michael McAlpine, the study’s lead researcher. “Someday we hope that we could have a 3D scanner and printer right at the hospital to create custom nerve guides right on site to restore nerve function.”
Scanning and printing takes about an hour, but the body needs several weeks to regrow the nerves. McAlpine said previous studies have shown regrowth of linear nerves, but this is the first time a study has shown the creation of a custom guide for regrowth of a complex nerve like the Y-shaped sciatic nerve that has both sensory and motor branches.
“The exciting next step would be to implant these guides in humans rather than rats,” McAlpine said. In cases where a nerve is unavailable for scanning, McAlpine said there could someday be a “library” of scanned nerves from other people or cadavers that hospitals could use to create closely matched 3D-printed guides for patients.