MIT engineers have been investigating sapwood’s natural filtering ability, and have previously fabricated simple filters from peeled cross-sections of sapwood branches, demonstrating that the low-tech design effectively filters bacteria.

Now, the same team has advanced the technology and shown that it works in real-world situations. They have fabricated new xylem filters that can filter out pathogens such as E. coli and rotavirus in lab tests, and have shown that the filter can remove bacteria from contaminated spring, tap, and groundwater. They also developed simple techniques to extend the filters’ shelf-life, enabling the woody disks to purify water after being stored in a dry form for at least two years.

The researchers took their techniques to India, where they made xylem filters from native trees and tested the filters with local users. Based on their feedback, the team developed a prototype of a simple filtration system, fitted with replaceable xylem filters that purified water at a rate of one liter per hour.

Their results, published today in Nature Communications, show that xylem filters have potential for use in community settings to remove bacteria and viruses from contaminated drinking water.

The researchers are exploring options to make xylem filters available at large scale, particularly in areas where contaminated drinking water is a major cause of disease and death. The team has launched an open-source website, with guidelines for designing and fabricating xylem filters from various tree types. The website is intended to support entrepreneurs, organizations, and leaders to introduce the technology to broader communities, and inspire students to perform their own science experiments with xylem filters.

“Because the raw materials are widely available and the fabrication processes are simple, one could imagine involving communities in procuring, fabricating, and distributing xylem filters,” says Rohit Karnik, professor of mechanical engineering and associate department head for education at MIT. “For places where the only option has been to drink unfiltered water, we expect xylem filters would improve health, and make water drinkable.”

Karnik’s study co-authors are lead author Krithika Ramchander and Luda Wang of MIT’s Department of Mechanical Engineering, and Megha Hegde, Anish Antony, Kendra Leith, and Amy Smith of MIT D-Lab.

Clearing the way

In their prior studies of xylem, Karnik and his colleagues found that the woody material’s natural filtering ability also came with some natural limitations. As the wood dried, the branches’ sieve-like membranes began to stick to the walls, reducing the filter’s permeance, or ability to allow water to flow through. The filters also appeared to “self-block” over time, building up woody matter that clogged the conduits.

Surprisingly, two simple treatments overcame both limitations. By soaking small cross-sections of sapwood in hot water for an hour, then dipping them in ethanol and letting them dry, Ramchander found that the material retained its permeance, efficiently filtering water without clogging up. Its filtering could also be improved by tailoring a filter’s thickness according to its tree type.

The researchers sliced and treated small cross-sections of white pine from branches around the MIT campus and showed that the resulting filters maintained a permeance comparable to commercial filters, even after being stored for up to two years, significantly extending the filters’ shelf life.

The researchers also tested the filters’ ability to remove contaminants such as E. coli and rotavirus — the most common cause of diarrheal disease. The treated filters removed more than 99 percent of both contaminants, a water treatment level that meets the “two-star comprehensive protection” category set by the World Health Organization.

“We think these filters can reasonably address bacterial contaminants,” Ramchander says. “But there are chemical contaminants like arsenic and fluoride where we don’t know the effect yet,” she notes.

Groundwork

Encouraged by their results in the lab, the researchers moved to field-test their designs in India, a country that has experienced the highest mortality rate due to water-borne disease in the world, and where safe and reliable drinking water is inaccessible to more than 160 million people.

Over two years, the engineers, including researchers in the MIT D-Lab, worked in mountain and urban regions, facilitated by local NGOs Himmotthan Society, Shramyog, Peoples Science Institute, and Essmart. They fabricated filters from native pine trees and tested them, along with filters made from ginkgo trees in the U.S., with local drinking water sources. These tests confirmed that the filters effectively removed bacteria found in the local water. The researchers also held interviews, focus groups, and design workshops to understand local communities’ current water practices, and challenges and preferences for water treatment solutions. They also gathered feedback on the design.

“One of the things that scored very high with people was the fact that this filter is a natural material that everyone recognizes,” Hegde says. “We also found that people in low-income households prefer to pay a smaller amount on a daily basis, versus a larger amount less frequently. That was a barrier to using existing filters, because replacement costs were too much.”

With information from more than 1,000 potential users across India, they designed a prototype of a simple filtration system, fitted with a receptacle at the top that users can fill with water. The water flows down a 1-meter-long tube, through a xylem filter, and out through a valve-controlled spout. The xylem filter can be swapped out either daily or weekly, depending on a household’s needs.

The team is exploring ways to produce xylem filters at larger scales, with locally available resources and in a way that would encourage people to practice water purification as part of their daily lives — for instance, by providing replacement filters in affordable, pay-as-you-go packets.

“Xylem filters are made from inexpensive and abundantly available materials, which could be made available at local shops, where people can buy what they need, without requiring an upfront investment as is typical for other water filter cartridges,” Karnik says. “For now, we’ve shown that xylem filters provide performance that’s realistic.”

The report appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

“Anabolic steroid use has been associated with a range of medical and psychological side effects,” said lead author, Astrid Bjørnebekk, PhD, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. “However, since anabolic steroids have only been in the public domain for about 35 years, we are still in the early phase of appreciating the full scope of effects after prolonged use. The least studied effects are those that relate to the brain.”

Steroid hormones readily enter the brain, and receptors for sex hormones are found throughout the brain. Because AAS are administered at much higher doses than those naturally found in the body, they could have a harmful impact on the brain, particularly over a long period of use. Previous studies have shown that AAS users performed worse on cognitive tests than non-users.

Dr. Bjørnebekk and colleagues performed magnetic resonance imaging (MRI) of the brains of 130 male weightlifters with a history of prolonged AAS use and of 99 weightlifters who had never used AAS. Using a set of data compiled from nearly 2,000 healthy males from age 18 to 92 years of age. The researchers used machine learning to determine the predicted brain age of each of their participants and then determined the brain age gap: the difference between each participant’s chronological age and their predicted brain age. Advanced brain age is associated with impaired cognitive performance and increased risk for neurodegenerative diseases.

Not surprisingly, AAS users had a bigger brain age gap compared to non-users. Those with dependence on AAS, or with a longer history of use, showed accelerated brain aging. The researchers accounted for use of other substances and for depression in the men, which did not explain the difference between the groups.

“This important study shows in a large sample that use is associated with deviant brain aging, with a potential impact on quality of life in older age. The findings could be directly useful for health care professionals, and may potentially have preventive implications, where brain effects are also included into the risk assessment for young men wondering whether to use anabolic steroids,” added Dr. Bjørnebekk.

Cameron Carter, MD, editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the study: “The results of this brain imaging study should be of concern for athletes using anabolic steroids for performance enhancement and suggest that the adverse effects on behavior and cognition previously shown to be associated with long-term use are the result of effects on the brain in the form of accelerated brain aging.”

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“Previous research has shown that disruption of the blood-brain barrier is increased in people with cerebral small vessel disease,” said study author Danielle Kerkhofs, M.D., of Maastricht University Medical Center in Maastricht, Netherlands. “People with cerebral small vessel disease also may have brain lesions called white matter hyperintensities. Such lesions are visible by MRI and believed to be signs of brain damage and a marker of the severity of disease. For our study, we wanted to see if a leaky blood-brain barrier was linked to degeneration of brain tissue even before these brain lesions appear. We looked at normal brain tissue, surrounding and close to the brain lesions, because we consider this ’tissue at risk.'”

The study involved 43 people with cerebral small vessel disease with an average age of 68. Researchers used MRI at the start of the study to measure the leakiness of the blood-brain barrier for each participant. They then used another brain imaging technique to measure the integrity of the tissue’s microstructure surrounding brain lesions. This imaging technique was repeated two years later to see whether the brain tissue integrity has decreased.

Researchers measured the relationship between blood-brain barrier leakage and changes in brain tissue. They found the higher the tissue volume with blood-brain barrier leakage at the start of the study, the greater the loss of brain tissue integrity was around brain lesions two years later. For every 10% increase in leakage volume at the start of the study, after two years the diffusivity of the brain tissue increased by 1.4 %, representing a decrease in brain tissue integrity. They also found a similar relationship involving the leakage rate of the blood-brain barrier — a higher leakage rate at the start of the study resulted in more loss of tissue microstructure around the brain lesions.

“Our results support the theory that a compromised blood-brain barrier may play an early role in loss of brain tissue integrity as part of the cerebral small vessel disease process, even before brain lesions are visible on MRI,” said Kerkhofs. “The change in integrity of brain tissue at risk, close to the brain lesions, could be a promising biomarker in future cerebral small vessel disease studies examining possible prevention strategies and treatment options.”

A limitation of the study was that the short follow-up period may have underestimated the associations. Kerkhofs said future studies should measure such changes in larger groups of people over longer periods of time.

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Following the team’s previous research, which identified that the concentration of specific molecules in saliva changes rapidly after a traumatic brain injury, the researchers embarked on a three-year study in elite rugby to establish if these ‘biomarkers’ could be used as a diagnostic test for sport-related concussion.

Using DNA sequencing technology in the laboratory at the University of Birmingham, the research team tested these biomarkers in saliva samples from 1,028 professional men’s rugby players competing in English rugby’s top two leagues — the Premiership and Championship.

The results of SCRUM (Study of Concussion in Rugby Union through MicroRNAs), published today (March 23) in the British Journal of Sports Medicine, has for the first time shown that specific salivary biomarkers can be used to indicate if a player has been concussed. Additionally, the research has found these biomarkers provide further insights into the body’s response to injury as it evolves from immediately after trauma, to several hours and even days later.

The scientific breakthrough provides a new laboratory-based non-invasive salivary biological concussion test, which could have wide-reaching use and potential to reduce the risk of missing concussions not only in sport — from grassroots to professional levels — but also in wider settings such as military and healthcare.

In community sport, these biomarkers may provide a diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting. While, at an elite level of rugby, the concussion test may be used in addition to the existing World Rugby Head Injury Assessment (HIA) protocol.

Marker Diagnostics, a subsidiary of Swiss biotechnology company Marker AG, is in the process of commercialising the patented salivary concussion test as an over-the-counter test for elite male athletes. It has also obtained a CE Mark for test, which has been named MDx.100.

The team now aims to collect further samples from players in two elite men’s rugby competitions in order to provide additional data to expand the test and develop its use to guide the prognosis and safe return to play after concussion and to further establish how it will work alongside the HIA process.

The team will present their findings and planned next research steps at the World Rugby Laws and Welfare Symposium to be held later this month.

Meanwhile, Marker Diagnostics and the University of Birmingham are also currently carrying out several additional studies to further validate and expand the test for use in different groups that were not included in the SCRUM study, including women, young athletes and community sports players.

The research is part of the REpetitive COncussion in Sport (ReCoS) research programme being led by the University of Birmingham through the National Institute for Health Research’s Surgical Reconstruction and Microbiology Research Centre (NIHR SRMRC) based at University Hospitals Birmingham NHS Foundation Trust (UHB).

First author Dr Valentina Di Pietro, of the University of Birmingham and NIHR SRMRC, said: “Concussion can be difficult to diagnose, particularly in settings such as grass roots sports where evaluation by a specialist clinician is not possible. Consequently, some concussions may go undiagnosed.

“There are also concerns regarding the long-term brain health of those exposed to repeated concussions.

“A non-invasive and accurate diagnostic test using saliva is a real game changer and may provide an invaluable tool to help clinicians diagnose concussions more consistently and accurately.

“In professional sports, this diagnostic tool may be used in addition to current head injury assessment protocols and return to play evaluation to ensure the safety of individuals.”

Senior author Antonio Belli, Professor of Trauma Neurosurgery at the University of Birmingham, Consultant Neurosurgeon at UHB, and Director of NIHR SRMRC, added: “Conducting a study in a professional contact sports setting has meant we have been able to collect invaluable data enabling us to make significant advances in our biological knowledge and understanding of concussion and its diagnosis.

“Crucially, the differences in the salivary concentration of these biomarkers are measurable within minutes of injury, which means we can make rapid diagnoses.

“The ability to rapidly diagnose concussion using biomarkers in addition to existing tools solves a major unmet need in the sporting world as well as in military and healthcare settings, particularly in injuries without significant visible symptoms.”

Author Dr Simon Kemp, RFU’s Medical Services Director, said: “This study is an important part of the portfolio of collaborative research initiatives the RFU undertakes into concussion.

“While still a way from having something that can be used in community rugby, it is extremely encouraging to now be able to start to develop a rapid and non-invasive test which could add real value particularly at a grassroots level of the game.

“We would like to thank all the players and clubs who participated in the study and to World Rugby for granting permission for us to extend the duration of the HIA from 10 to 13 minutes in order for the saliva samples to be captured. We wouldn’t have been able to do it without this support.

“We will now be working with World Rugby to secure further research options in two elite men’s competitions.”

Author Dr Matt Cross, Head of Science and Medical Operations at Premiership Rugby, said: “We would like to thank our clubs and all of the players for volunteering to be part of this very important research project.

“The findings from the study are clearly promising and highlight the potential for salivary biomarkers to further support clinical decision making and the accurate identification and diagnosis of concussion in a range of different sporting and non-sporting settings.

“Premiership Rugby and the Premiership clubs support a number of player welfare focused research projects, and we are looking forward to continuing to collaborate and support further research in the next phase of this specific project from 2021-22 onwards.”

Dr Éanna Falvey, World Rugby Chief Medical Officer, added: “Elite Rugby’s Head Injury Assessment process has proven an invaluable tool in the identification of concussion with an accuracy of over 90 per cent, but we are continually evaluating the latest developments in science and technology to identify potential enhancements.

“This study, its rigour and outcomes demonstrates the value in a targeted, scientific approach and reflects rugby’s progressive commitment to player welfare.”

Tinus Maree, CEO of Marker AG, said: “This ground-breaking validation of the biomarker panel shows that we can use the simple swab collection of saliva to accurately and specifically diagnose concussion.

“It is a biological measure of mild traumatic brain injury and will contribute to a new global standard of care for the injury and a meaningful reduction of the cost and health burden associated with concussion.

“We are grateful to our collaborators, especially to Dr Simon Kemp and the RFU, for their efforts and visionary support of this important work.”

The study, fully supported by The Rugby Players’ Association, saw the team obtaining saliva samples from male professional players in the top two tiers of England’s elite rugby union competition during the 2017-18 and 2018-19 rugby seasons.

Saliva samples were collected pre-season from 1,028 players. They were also collected from 156 of these players during standardised World Rugby head injury assessments (HIAs) at three time points — in-game, post-game, and 36-48 hours post-game. The HIA protocol, used by rugby medical staff, includes a neurological examination, a series of cognitive tests and evaluation of gait and balance to determine if a player has been concussed.

‘Control’ samples were also collected from 102 uninjured players and 66 players who were removed from the game due to musculoskeletal injuries.

Using samples collected during the 2017-18 season, the team identified a panel of a combination of 14 salivary biomarkers — known as small non-coding RNAs or sncRNAs — that was highly accurate (96%) at identifying concussed players from all other groups.

This included players with suspicion of mild traumatic brain injury who had a concussion ruled out after a structured HIA; uninjured controls from the same game; and players who had suffered musculoskeletal injuries.

The panel was prospectively tested during the 2018-19 season, and the research showed it could successfully predict whether players would be positive or negative for concussion via the HIA protocol in 94% of cases.

The study was funded by the Midland Neurosciences Teaching and Research Fund, NIHR SRMC, Medical Research Council, Rugby Football Union and Marker AG.