The new approach, reported in ACS' journal Analytical Chemistry, could be useful for medical applications in regions of the world that lack electricity and other resources. Before doctors can perform many types of blood tests, they must separate blood cells from plasma, the yellowish fluid that contains proteins, bacteria, viruses, metabolites and other substances that can be used to diagnose disease. This is most often accomplished by centrifugation, which uses high-speed rotation to sediment blood cells. However, centrifuges are expensive and require electricity that might not be available in resource-limited regions. Chien-Fu Chen, Chien-Cheng Chang and colleagues wondered if a commercially available fidget-spinner could generate enough force to separate blood plasma with the flick of a finger. To find out, the researchers placed human blood samples in tiny tubes, sealed the ends and taped a tube to each of the three prongs of a fidget-spinner. They found that by flicking the spinner with a finger three to five times, they could separate about 30 percent of the plasma with 99 percent purity in only four to seven minutes. To verify that the plasma was suitable for diagnostic tests, the researchers spiked blood with a human immunodeficiency virus-1 (HIV-1) protein, separated the plasma with the spinner and performed a paper-based detection test. The inexpensive, simple method detected clinically relevant concentrations of the viral protein in only a drop of blood.
The study's findings appeared in EBioMedicine, a publication of The Lancet. "This test solves a long-standing problem in lung transplants: detection of hidden signs of rejection," said Hannah Valantine, M.D., co-leader of the study and lead investigator of the Laboratory of Organ Transplant Genomics in the Cardiovascular Branch at NHLBI. "We're very excited about its potential to save lives, especially in the wake of a critical shortage of donor organs." The test relies on DNA sequencing, Valantine explained, and as such, represents a great example of personalized medicine, as it will allow doctors to tailor transplant treatments to those individuals who are at highest risk for rejection. Lung transplant recipients have the shortest survival rates among patients who get solid organ transplantation of any kind - only about half live past five years. Lung transplant recipients face a high incidence of chronic rejection, which occurs when the body's immune system attacks the transplanted organ. Existing tools for detecting signs of rejection, such as biopsy, either require the removal of small amounts of lung tissue or are not sensitive enough to discern the severity of the rejection. The new test appears to overcome those challenges. Called the donor-derived cell-free DNA test, the experimental test begins with obtaining a few blood droplets taken from the arm of the transplant recipient. A special set of machines then sorts the DNA fragments in the blood sample, and in combination with computer analysis, determines whether the fragments are from the recipient or the donor and how many of each type are present. Because injured or dying cells from the donor release lots of donor DNA fragments into the bloodstream compared to normal donor cells, higher amounts of donor DNA indicate a higher risk for transplant rejection in the recipient. In the study, 106 lung transplant recipients were enrolled and monitored. Blood samples collected in the first three months after transplantation underwent the testing procedure. The results showed that those with higher levels of the donor-derived DNA fragments in the first three months of transplantation were six times more likely to subsequently develop transplant organ failure or die during the study follow-up period than those with lower donor-derived DNA levels. Importantly, researchers found that more than half of the high-risk subjects showed no outward signs of clinical complications during this period.
Vaccinations against polio, diphtheria, whooping cough and tetanus have been on the list of standard infant vaccinations for decades now. Many vaccines are inactivated vaccines - that is to say, the pathogens they contain have been killed so that they can no longer harm the patient. Despite this, the vaccine provokes an immune response: The body detects a foreign intruder and begins to produce antibodies to ward off infection. To produce these vaccines, pathogens are cultivated in large quantities and then killed using toxic chemicals. The most common of these is formaldehyde - heavily diluted so it doesn’t harm the patient when the vaccination is administered. Nevertheless, there are downsides to even this minimal concentration: The toxin must remain in contact with the pathogen for days or even weeks to take effect, which has a negative impact both on the structure of the pathogen and the reproducibility of the vaccine. And in cases that call for speed – flu vaccines for instance – drug manufacturers are obliged to use higher dosages of formaldehyde. The product must then undergo a time-consuming process of filtration to avoid traces of the toxic chemical being left behind in the vaccine. Electron beams kill harmful pathogens Now, pharmaceutical companies will be able to produce inactivated vaccines without the slightest trace of toxic chemicals – quickly and reproducibly. The scientists who developed this process see its greatest potential in the production of vaccines that until now were not amenable to the method of chemical inactivation. The technique was developed jointly by researchers at the Fraunhofer Institutes for Cell Therapy and Immunology IZI, Manufacturing Engineering and Automation IPA, Organic Electronics, Electron Beam and Plasma Technology FEP and Interfacial Engineering and Biotechnology IGB. “Instead of using chemicals to inactivate the pathogens, we employ low-energy electron beams,” explains Fraunhofer IPA team leader Martin Thoma. The accelerated electrons break down the DNA of the pathogens either via direct collisions or through the generation of secondary electrons, which subsequently result in single or double strand breaks. In a nutshell, the electrons fragment the pathogens’ DNA while maintaining their external structure. This is important to trigger an effective immune response. The challenge arises from the fact that the electrons cannot penetrate very deeply into the suspension containing the pathogens - in fact, for an even dose distribution, liquid levels should not exceed 200 micrometers. Because there were no existing technologies capable of meeting these requirements, Fraunhofer IPA developed two new methods from scratch. In the first method, a cylinder is continuously wetted with the pathogen suspension, irradiated, and the inactivated liquid transferred into a sterile vessel. In other words, there are two reservoirs of liquid: one containing the active and one containing the inactive pathogens - connected to one another via a constantly turning cylindrical vessel or tumbler. “It’s a continuous process that can easily be scaled up for the mass production of vaccines,” says Thoma. The second method is more suited to lab-scale applications, in which small quantities of vaccine are produced for research or drug development purposes. In this instance, the solution containing the pathogens is placed in bags, which are then passed through the electron beam using a patented process. A collaborative undertaking This kind of project calls for a range of expertise that is perfectly covered by the four Fraunhofer Institutes involved in the initiative. Researchers at Fraunhofer IZI took responsibility for cultivating the various pathogens – including one for avian flu and one for equine influenza. “Following the irradiation, we also worked with our colleagues at Fraunhofer IGB to determine whether the pathogens had been fully inactivated, thus providing effective vaccine protection,” says Dr. Sebastian Ulbert, head of department at Fraunhofer IZI and the initiator of the project. The expertise in electron beam technology came from researchers at Fraunhofer FEP, who developed a system capable of delivering the low-energy electron beams at precise doses – this is necessary because, while the aim is to reliably inactivate the pathogen, care must also be taken to preserve the pathogen structure so that patients’ immune systems can produce the corresponding antibodies. The new technology has already been implemented, and not only on the laboratory scale: “In the fall of 2018, a research and pilot facility entered into service here at Fraunhofer IZI. Using our continuous module – the wetted tumbler – we are currently able to produce four liters of vaccine per hour,” says Ulbert. That is not far off industrial scale, given that, for certain vaccines, 15 liters of pathogen suspension can yield a million doses of vaccine. Discussions are already underway with partners in industry. However, it will be another two to four years before vaccines produced using electron beams can be tested in clinical trials.
This technique has proven to be successful, although the specific reasons for its success were not fully understood. A team of researchers led by Konstantin Bergmeister and Oskar Aszmann from the Division of Plastic and Reconstructive Surgery and the Christian Doppler Laboratory for Recovery of Limb Function at MedUni Vienna, demonstrated, in an animal model, that the key to success lies in the muscle undergoing a change of identity triggered by the donor nerve. Bionic prostheses are mentally controlled, in that they register the activation of residual muscles in the limb stump. Theoretically it should be possible for the latest generation prostheses to execute the same number of movements as a healthy human hand. However, the link between man and prosthesis is not yet capable of controlling all mechanically possible functions, because the interface between man and prostheses is limited in terms of signal transmission. "If we could solve this problem, the latest prostheses could actually become an intuitively operated replacement that functions just like a human hand," underscore the researchers. To enable the prosthesis to move at all, nerves have to be surgically transferred during the amputation procedure to increase the total number of muscle control signals. This involves connecting amputated peripheral nerves to residual muscles in the amputation stump. This method is very successful, because these muscles regenerate after a few months to provide better control of the prosthesis. However, until now, it was not clear what specific changes this nerve transfer technique produces in muscles and nerves. As part of an experimental study conducted over several years, a research team led by Konstantin Bergmeister and Oskar Aszmann from MedUni Vienna’s Division of Plastic and Reconstructive Surgery (Head: Christine Radtke) and Christian Doppler Laboratory for Recovery of Limb Function have now shown that this nerve transfer technique has previously unidentified neurophysiological effects. These result in more accurate muscle contractility and much more finely controlled muscle signals than previously thought. It was also found that muscles take on the identity of the donor nerves, that is to say the function of the muscle from which the nerve was originally harvested. This means that muscles can be modified very specifically to achieve the desired control of the lost extremity. This information will now be used in follow-up studies to refine the surgical technique of nerve transfer and adapt it more accurately to fine control systems. The vision of an intuitively controlled prosthesis that can perform all the natural manual functions could become a reality within the next few years.
It navigates through rooms and around obstacles to find people on its own, provides video instructions on how to do simple tasks and can even lead its owner to objects like their medication or a snack in the kitchen. "RAS combines the convenience of a mobile robot with the activity detection technology of a WSU smart home to provide assistance in the moment, as the need for help is detected," said Bryan Minor, a postdoctoral researcher in the WSU School of Electrical Engineering and Computer Science. Minor works in the lab of Diane Cook, professor of electrical engineering and computer science and director of the WSU Center for Advanced Studies in Adaptive Systems. For the last decade, Cook and Maureen Schmitter-Edgecombe, a WSU professor of psychology, have led CASAS researchers in the development of smart home technologies that could enable elderly adults with memory problems and other impairments to live independently. Currently, an estimated 50 percent of adults over the age of 85 need assistance with every day activities such as preparing meals and taking medication and the annual cost for this assistance in the US is nearly $2 trillion. With the number of adults over 85 expected to triple by 2050, Cook and Schmitter-Edgecombe hope that technologies like RAS and the WSU smart home will alleviate some of the financial strain on the healthcare system by making it easier for older adults to live alone. "Upwards of 90 percent of older adults prefer to age in place as opposed to moving into a nursing home," Cook said. "We want to make it so that instead of bringing in a caregiver or sending these people to a nursing home, we can use technology to help them live independently on their own." RAS is the first robot CASAS researchers have tried to incorporate into their smart home environment. They recently published a study in the journal Cognitive Systems Research that demonstrates how RAS could make life easier for older adults struggling to live independently. CASAS researchers recruited 26 undergraduate and graduate students to complete three activities in a smart home with RAS as an assistant. The activities were getting ready to walk the dog, taking medication with food and water and watering household plants. When the smart home sensors detected a human failed to initiate or was struggling with one of the tasks, RAS received a message to help. The robot then used its mapping and navigation camera, sensors and software to find the person and offer assistance. The person could then indicate through a tablet interface that they wanted to see a video of the next step in the activity they were performing, a video of the entire activity or they could ask the robot to lead them to objects needed to complete the activity like the dog's leash or a granola bar from the kitchen. Afterwards the study participants were asked to rate the robot's performance. Most of the participants rated RAS' performance favorably and found the robot's tablet interface to be easy to use. They also reported the next step video as being the most useful of the prompts. "While we are still in an early stage of development, our initial results with RAS have been promising," Minor said. "The next step in the research will be to test RAS' performance with a group of older adults to get a better idea of what prompts, video reminders and other preferences they have regarding the robot."
The implants, described in a study published in the January 14 issue of Nature Medicine, are intended to promote nerve growth across spinal cord injuries, restoring connections and lost function. In rat models, the scaffolds supported tissue regrowth, stem cell survival and expansion of neural stem cell axons out of the scaffolding and into the host spinal cord. "In recent years and papers, we've progressively moved closer to the goal of abundant, long-distance regeneration of injured axons in spinal cord injury, which is fundamental to any true restoration of physical function," said co-senior author Mark Tuszynski, MD, PhD, professor of neuroscience and director of the Translational Neuroscience Institute at UC San Diego School of Medicine. Axons are the long, threadlike extensions on nerve cells that reach out to connect to other cells. "The new work puts us even closer to real thing," added co-first author Kobi Koffler, PhD, assistant project scientist in Tuszynski's lab, "because the 3D scaffolding recapitulates the slender, bundled arrays of axons in the spinal cord. It helps organize regenerating axons to replicate the anatomy of the pre-injured spinal cord." Co-senior author Shaochen Chen, PhD, professor of nanoengineering and a faculty member in the Institute of Engineering in Medicine at UC San Diego, and colleagues used rapid 3D printing technology to create a scaffold that mimics central nervous system structures. "Like a bridge, it aligns regenerating axons from one end of the spinal cord injury to the other. Axons by themselves can diffuse and regrow in any direction, but the scaffold keeps axons in order, guiding them to grow in the right direction to complete the spinal cord connection," Chen said. The implants contain dozens of tiny, 200-micrometer-wide channels (twice the width of a human hair) that guide neural stem cell and axon growth along the length of the spinal cord injury. The printing technology used by Chen's team produces two-millimeter-sized implants in 1.6 seconds. Traditional nozzle printers take several hours to produce much simpler structures. The process is scalable to human spinal cord sizes. As proof of concept, researchers printed four-centimeter-sized implants modeled from MRI scans of actual human spinal cord injuries. These were printed within 10 minutes. "This shows the flexibility of our 3D printing technology," said co-first author Wei Zhu, PhD, nanoengineering postdoctoral fellow in Chen's group. "We can quickly print out an implant that's just right to match the injured site of the host spinal cord regardless of the size and shape." Researchers grafted the two-millimeter implants, loaded with neural stem cells, into sites of severe spinal cord injury in rats. After a few months, new spinal cord tissue had regrown completely across the injury and connected the severed ends of the host spinal cord. Treated rats regained significant functional motor improvement in their hind legs. "This marks another key step toward conducting clinical trials to repair spinal cord injuries in people," Koffler said. "The scaffolding provides a stable, physical structure that supports consistent engraftment and survival of neural stem cells. It seems to shield grafted stem cells from the often toxic, inflammatory environment of a spinal cord injury and helps guide axons through the lesion site completely."
In a paper published in PLOS ONE, scientists from the University of Surrey's Centre for Vision, Speech and Signal Processing (CVSSP) detail how, in an NHS clinical trial, they used a technique called Non-negative Matrix Factorisation to find hidden clues of possible UTI cases. The team then used novel machine learning algorithms to identify early UTI symptoms. The experiment was part of the TIHM (Technology Integrated Health Management) for dementia project, led by Surrey and Borders Partnership NHS Foundation Trust and in partnership with the University of Surrey and industry collaborators. The project, which is part of the NHS Test Beds Programme and is funded by NHS England the Office for Life Sciences, allowed clinicians to remotely monitor the health of people with dementia living at home, with the help of a network of internet enabled devices such as environmental and activity monitoring sensors, and vital body signal monitoring devices. Data streamed from these devices was analysed using machine learning solutions, and the identified health problems were flagged on a digital dashboard and followed up by a clinical monitoring team. According to The World Health Organisation, around 50 million people worldwide have dementia. This number is estimated to reach 82 million in 2030 and 152 million in 2050. According to the Alzheimer's Society, one in four hospital beds in the UK are occupied by a person with dementia, while around 22 percent of these admissions are deemed to be preventable. Payam Barnaghi, Professor of Machine Intelligence at CVSSP, said: "Urinary tract infections are one of the most common reasons why people living with dementia go into hospital. We have developed a tool that is able to identify the risk of UTIs so it is then possible to treat them early. We are confident our algorithm will be a valuable tool for healthcare professionals, allowing them to produce more effective and personalised plans for patients." Professor Adrian Hilton, Director of CVSSP, said: "This development hints at the incredible potential of Professor Barnaghi's research here at CVSSP. Machine learning could provide improved care for people living with dementia to remain at home, reducing hospitalization and helping the NHS to free up bed space." Dr Shirin Enshaeifar, Senior Research Fellow at CVSSP, said: "I am delighted to see that the algorithms we have designed have an impact on improving the healthcare of people with dementia and providing a tool for clinicians to offer better support to their patients." Professor Helen Rostill, Director of Innovation and Development at Surrey and Borders Partnership NHS Foundation Trust, said: "The TIHM for dementia study is a collaborative project that has brought together the NHS, academia and industry to transform support for people with dementia living at home and their carers. Our aim has been to create an Internet of Things led system that uses machine learning to alert our clinicians to potential health problems that we can step in and treat early. The system helps to improve the lives of people with dementia and their carers and could also reduce pressure on the NHS."
Certain bacteria and viruses can harness the cells' motility machinery to invade our bodies. Understanding how cells move – and the rod-like actin filaments that drive the process – is key to learning how to halt or promote motility to improve human health. Now, using one of the most powerful microscopes in the world, scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP) and University of North Carolina at Chapel Hill (UNC-Chapel Hill) have identified a dense, dynamic and disorganized actin filament nanoscaffold – resembling a haystack – that is induced in response to a molecular signal. This is the first time researchers have directly visualized, at the molecular level, a structure that is triggered in response to a cellular signal – a key finding that expands our understanding of how cells move. The study was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS). "Cyro-electron microscopy is revolutionizing our understanding of the inner workings of cells," says Dorit Hanein, Ph.D., senior author of the paper and professor in the Bioinformatics and Structural Biology Program at SBP. "This technology allowed us to collect robust, 3D images of regions of cells – similar to MRI, which creates detailed images of our body. We were able to visualize cells in their natural state, which revealed a never-before-seen actin nano-architecture within the cell." In the study, the scientists used SBP's cryo-electron microscope (Titan Krios), artificial intelligence (AI) and tailor-made computational and cell imaging approaches to compare nanoscale images of mouse fibroblasts to time-stamped light images of fluorescent Rac1, a protein that regulates cell movement, response to force or strain (mechanosensing) and pathogen invasion. The images revealed a densely packed, disorganized, scaffold-like structure comprised of short actin rods. These structures sprang into view in defined regions where Rac1 was activated, and quickly dissipated when Rac1 signaling stopped – in as little as two and a half minutes. This dynamic scaffold contrasted sharply with various other actin assemblies in areas of low Rac1 activation – some comprised of long, aligned rods of actin, and others comprised of short actin rods branching from the sides of longer actin filaments. The volume encasing the actin scaffold was devoid of common cellular structures, such as ribosomes, microtubules, vesicles and more, likely due to the structure's intense density. Next, the scientists would like to expand the protocol to visualize more structures that are created in response to other molecular signals and to further develop the technology to allow access to other regions of the cell. "This study is only the beginning. Now that we developed this quantitative nanoscale workflow that correlates dynamic signaling behavior with the nano-scale resolution of electron cryo-tomography, we and additional scientists can implement this powerful analytical tool not only for deciphering the inner workings of cell movement but also for elucidating the dynamics of many other macromolecular machines in an unperturbed cellular environment," says Hanein. She adds, "Actin is a building-block protein; it interacts with more than 150 actin binding proteins to generate diverse structures, each serving a unique function. We have a surplus of different signals that we would like to map, which could yield even more insights into how cells move." MEDICA-tradefair.com; Source: Sanford Burnham Prebys Medical Discovery Institute (SBP)
The device, named the WAND, works like a "pacemaker for the brain," monitoring the brain's electrical activity and delivering electrical stimulation if it detects something amiss. These devices can be extremely effective at preventing debilitating tremors or seizures in patients with a variety of neurological conditions. But the electrical signatures that precede a seizure or tremor can be extremely subtle, and the frequency and strength of electrical stimulation required to prevent them is equally touchy. It can take years of small adjustments by doctors before the devices provide optimal treatment. WAND, which stands for wireless artifact-free neuromodulation device, is both wireless and autonomous, meaning that once it learns to recognize the signs of tremor or seizure, it can adjust the stimulation parameters on its own to prevent the unwanted movements. And because it is closed-loop - meaning it can stimulate and record simultaneously - it can adjust these parameters in real-time. "The process of finding the right therapy for a patient is extremely costly and can take years. Significant reduction in both cost and duration can potentially lead to greatly improved outcomes and accessibility," said Rikky Muller, assistant professor of electrical engineering and computer sciences at Berkeley. "We want to enable the device to figure out what is the best way to stimulate for a given patient to give the best outcomes. And you can only do that by listening and recording the neural signatures." WAND can record electrical activity over 128 channels, or from 128 points in the brain, compared to eight channels in other closed-loop systems. To demonstrate the device, the team used WAND to recognize and delay specific arm movements in rhesus macaques. The device is described in a study that appeared in Nature Biomedical Engineering.
Chronic skin wounds include diabetic foot ulcers, venous ulcers and non-healing surgical wounds. Doctors have tried various approaches to help chronic wounds heal, including bandaging, dressing, exposure to oxygen and growth-factor therapy, but they often show limited effectiveness. As early as the 1960s, researchers observed that electrical stimulation could help skin wounds heal. However, the equipment for generating the electric field is often large and may require patient hospitalization. Weibo Cai, Xudong Wang and colleagues wanted to develop a flexible, self-powered bandage that could convert skin movements into a therapeutic electric field. To power their electric bandage, or e-bandage, the researchers made a wearable nanogenerator by overlapping sheets of polytetrafluoroethylene (PTFE), copper foil and polyethylene terephthalate (PET). The nanogenerator converted skin movements, which occur during normal activity or even breathing, into small electrical pulses. This current flowed to two working electrodes that were placed on either side of the skin wound to produce a weak electric field. The team tested the device by placing it over wounds on rats' backs. Wounds covered by e-bandages closed within 3 days, compared with 12 days for a control bandage with no electric field. The researchers attribute the faster wound healing to enhanced fibroblast migration, proliferation and differentiation induced by the electric field.