Chung-Ang University researchers breathe life into sensors with versatile gas masks

The researchers developed a novel self-powered device that is driven by respiration, allowing them to be integrated with gas masks

Peer-Reviewed Publication

CHUNG ANG UNIVERSITY

 

IMAGE: IN A NEW STUDY, CHUNG-ANG UNIVERSITY RESEARCHERS DESIGN A HIGH-POWER AND HIGH OUTPUT TRIBOELECTRIC NANOGENERATOR (TENG)-BASED SENSOR THAT CAN BE POWERED BY BREATHING. THE RESEARCHERS INTEGRATED THIS DEVICE INTO A GAS MASK TO CREATE A SELF-POWERED HYBRID SENSOR THAT DETECTS BREATHING PATTERNS AND HARMFUL CHEMICALS. view more 

CREDIT: PROF. SANGMIN LEE FROM CHUNG-ANG UNIVERSITY, KOREA

With the onset of the Internet of Things (IoT) era, devices have learned to communicate and exchange data. This is achieved through sensors installed in physical objects, machines, and equipment. The sensors can detect changes in events. However, the need for continuous energy supply to these sensors poses a challenge. Batteries are bulky, expensive, and not environmentally friendly. Additionally, they need to be constantly replaced or recharged.

Consequently, there is a demand for sustainable and renewable energy sources to replace batteries. The triboelectric nanogenerator (TENG) is one such device. Put simply, TENGs convert mechanical energy into electrical energy. Their high energy efficiency, compatibility with readily available materials, and low cost make them a promising candidate for powering sensors.

Despite such advantages, however, current TENGs are limited by a low output current. But increasing the output current would require larger equipment, making it impossible to be used in small devices. Is there a way around this trade-off?

Fortunately, a research team led by Associate Professor Sangmin Lee from Chung-Ang University in Korea, has now addressed this issue. “Our lab is interested in high-power TENG design and TENG-based self-powered sensors. We sought to address the limitation of current TENGs so that they could be used to realize portable power sources in practice,” says Dr. Lee, explaining his motivation behind the study, which was published online on May 31, 2022 in Advanced Energy Materials. The study will be featured on the front cover of the upcoming issue.

The team developed a novel device in their study called “inhalation-driven vertical flutter TENG” (IVF-TENG) which exhibits an amplified current output. "Respiration acts as a continuous mechanical input and can be used to operate TENGs. Film-flutter TENGs are such respiration-driven devices that can generate a continuous electrical output from an extremely small respiration input by exploiting the flutter phenomenon arising from airflow-induced vibrations,” explains Dr. Lee.

The IVF-TENG is composed of an aluminium (Al) inlet electrode, an aeroelastic dielectric sheet (polyimide), and an Al outlet electrode. The aeroelastic sheet has four segments with four slits and is subjected to vertical flutter behavior caused by airflow. This makes the proposed IVF-TENG different from existing TENGs.

The team investigated the electrical and mechanical mechanisms of IVF-TENG. They found that IVF-TENG generated a continuous, high-frequency electrical voltage (17 V) and a closed-circuit current of 1.84 μA during inhalation, and an electrostatic discharge voltage of 456 V and closed-circuit output current of 288 mA at the beginning and end of every inspiratory cycle.

They further demonstrated that IVF-TENG can continuously power 130 LEDs in series and 140 LEDs in parallel in every inhalation. Additionally, it could charge a 660 𝜇F capacitor to, in turn, power a Bluetooth tracker and provide its signal to a smartphone. These properties demonstrated the potential for IVF-TENG’s application in portable electronics and wireless data transmission.

Furthermore, the researchers integrated IVF-TENG into a gas mask and demonstrated its ability to monitor the breathing pattern of the user by observing the output response waveform. Moreover, it could detect chemical warfare agents like cyanogen chloride, sarin, and dimethyl methylphosphonate (DMMP), showing its potential for use during emergencies. “Since gas masks are extensively used in emergencies like fire and chemical gas exposure, we focused on applying TENG to a gas mask. We believe that IVF-TENG can be used as a self-powered sensor in such scenarios,” Dr. Lee speculates.

Indeed, their invention could make TENGs reinvent gas masks as a self-powered hybrid sensing system in the near future!

 

***

Reference

DOI: https://doi.org/10.1002/aenm.202201001

Authors: Deokjae Heo1, Myunghwan Song1, Seh-Hoon Chung1, Kyunghwan Cha1, Youna Kim2, Jihoon Chung2, Patrick T.J. Hwang3, Jaeheon Lee4, Heesoo Jung4, Youngho Jin4, Jinkee Hong2, Min-Kun Kim4, and Sangmin Lee1

Affiliations:
1School of Mechanical Engineering, Chung-Ang University
2Department of Chemical & Biomolecular Engineering, College of Engineering, Yonsei University
3Department of Biomedical Engineering, The University of Alabama at Birmingham
4Agency for Defense Development, Chem-Bio Technology Center

 

About Chung-Ang University
Chung-Ang University is a private comprehensive research university located in Seoul, South Korea. It was started as a kindergarten in 1916 and attained university status in 1953. It is fully accredited by the Ministry of Education of Korea. Chung-Ang University conducts research activities under the slogan of “Justice and Truth.” Its new vision for completing 100 years is “The Global Creative Leader.” Chung-Ang University offers undergraduate, postgraduate, and doctoral programs, which encompass a law school, management program, and medical school; it has 16 undergraduate and graduate schools each. Chung-Ang University’s culture and arts programs are considered the best in Korea.
Website: https://neweng.cau.ac.kr/index.do

 

About Associate Professor Sangmin Lee                                       
Dr. Sangmin Lee received his Ph.D. in Mechanical Engineering from Pohang University of Science and Technology (POSTECH) in 2011. He teaches at Chung-Ang University where he is an Associate Professor in the School of Mechanical Engineering. His group researches in the field of energy harvesting based on electrostatic potential, piezoelectric/triboelectric nanogenerators, and hybrid cells. His research interests also lie in surface wetting control including superhydrophobicity/superhydrophilicity based on micro and nanofabrications, and mechanical characterization of micro and nanostructures surfaces.

Read more about Prof. Lee here: https://scholarworks.bwise.kr/cau/researcher-profile?ep=919

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JOURNAL

Advanced Energy Materials

DOI

10.1002/aenm.202201001 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Inhalation-Driven Vertical Flutter Triboelectric Nanogenerator with Amplified Output as a Gas-Mask-Integrated Self-Powered Multifunctional System

Swarms of microrobots could be solution to unblocking medical devices in body

Peer-Reviewed Publication

UNIVERSITY OF ESSEX

 

IMAGE: DR ALI HOSHIAR WORKING IN HIS MICROBIOTICS LAB AT THE UNIVERSITY OF ESSEX view more 

CREDIT: UNIVERSITY OF ESSEX

Swarms of microrobots injected into the human body could unblock internal medical devices and avoid the need for further surgery, according to new research from the University of Essex.

The study is the first-time scientists have developed magnetic microrobotics to remove deposits in shunts – common internal medical devices used to treat a variety of conditions by draining excess fluid from organs.

Shunts are prone to malfunctioning, often caused by blockages due to a build-up of sediment. The sediment not only narrows and obstructs liquid passing through the shunt, but it also affects the shunt’s flexibility. This leads to patients needing repeated, invasive surgeries throughout their lives either to replace the shunt or use a catheter to remove the blockage.

However, this new research, led by microrobotics expert Dr Ali Hoshiar, from Essex’s School of Computer Science and Electronic Engineering, has shown there could be a wireless, non-invasive alternative to clearing the blockage in a shunt.

Published in the IEEE Transaction on Biomedical Engineering journal, Dr Hoshiar and his team have shown that a swarm of hundreds of microrobots – made of nano size magnetic nanoparticles – injected into the shunt could remove the sediment instead.

“Once the magnetic microrobots are injected into the shunt they can be moved along the tube to the affected area using a magnetic field, generated by a powerful magnet on the body’s surface,” explained Dr Hoshiar. “The swarm of microrobots can then be moved so they scrape away the sediment, clearing the tube.

“The non-invasive nature of this method is a considerable advantage to existing methods as it will potentially eliminate the risk of surgery and a surgery-related infection, thereby decreasing recovery time.”

With each microrobot smaller than the width of a human hair, once the swarm has done its job, it can either be guided to the stomach via a magnetic field or bodily fluid, so they leave the body naturally. Because the microrobots have very high biocompatibility they will not cause toxicity.

The research also found a direct relation between the strength of the magnetic field and the success of scraping away the sediment in the shunt.

This is the first proof-of-concept experiment using microswarms for opening a blockage in a shunt. The next stage of this research is to work with clinicians to carry out trials. The researchers are also looking at how the concept can be used to other applications.

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JOURNAL

IEEE Transactions on Biomedical Engineering

DOI

10.1109/TBME.2022.3192807 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

A novel non-invasive intervention for removing occlusions from shunts using an abrading magnetic microswarm

Noise affects life on the seafloor

Sounds with low frequencies stress some species of crustaceans, worms and mussels - with potentially far-reaching consequences for marine ecosystems

Peer-Reviewed Publication

ALFRED WEGENER INSTITUTE, HELMHOLTZ CENTRE FOR POLAR AND MARINE RESEARCH

 

IMAGE: PARTICLES GLOWING UNDER UV LIGHT WERE USED TO VISUALIZE THE ANIMALS' DIGGING ACTIVITIES view more 

CREDIT: ALFRED WEGENER INSTITUTE / SHENG WANG

Oceans have their own unique soundscape. Many marine organisms, for example, use sound for echolocation, navigation or communication with conspecifics. In recent decades, however, more and more sounds caused by human activities are permeating the waters. A study by the Alfred Wegener Institute now presents evidence that these sounds affect some invertebrates that live in and on the seafloor in ways that important functions they provide for their ecosystems may be impacted.

Invertebrates such as crustaceans, mussels and worms are ecosystem engineers. They continually change the sediment they live in by burrowing, feeding, aerating and fertilizing with their excreta. These activities are critical to nutrient cycling in the ocean, allowing more carbon from dead organic material to be stored in the seafloor and nutrients to be recycled.

Rising temperatures, ocean acidification and pollutants are placing organisms in marine ecosystems under increasing stress. In recent decades, noises caused by human activities have also increasingly contributed to the problem, affecting the behavior, foraging or communication of marine animals. Sounds from blasting and resource extraction roar through the oceans along with the loud drone of cargo ships and recreational boats. A research team from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) in Bremerhaven has now shown in a study published in the journal Environmental Pollution that these sounds stress not only marine mammals, but also invertebrates. “We investigated how crustaceans, mussels and worms on the seafloor respond to low-frequency noise and how frequently and intensively they are able to transform and break down sediment during noise exposure,” says Sheng V. Wang from the Department of Biosciences at AWI. Low-frequency noise is sound with frequencies between 10 and 500 hertz and in water, these sounds can be transmitted over many kilometers.

Despite the constant rise in noise pollution caused by human activities, little is known about how noise affects invertebrates on the seafloor. To help fill this research gap, AWI scientists studied in the laboratory how amphipods, lugworms, and Baltic clams are affected by sound waves with frequencies between 100 and 200 hertz using so-called “noise eggs”. “After six days, we could clearly see that all three species responded to the noise even though they belong to very different groups of animals that lack actual organs for hearing,” says AWI ecologist Dr. Jan Beermann. For example, the amphipods burrowed significantly less and not as deep into the sediment. No clear response was observed for the lugworms but they seemed to behave more inconsistently. Potential stress responses were noted for the Baltic clams which need to be further investigated. The researchers stress the urgent need for field research, however, as experimental setups under laboratory conditions do not encompass the full complexity of nature.

That additional man-made noise could inhibit seafloor invertebrates from cultivating and restructuring sediments may affect important functions of marine ecosystems, from nutrient supply to food availability for those higher up in the food web such as fish. “Things could get even 'noisier' on the seafloor due to human activities,” Beermann says. “We are just beginning to understand how exactly noise processes work here. Understanding this, however, is crucial for the sustainable use of our oceans,” which is why the team plans to conduct further research in this area. Experiments at other AWI sites such as Helgoland and Sylt are also to provide more detailed findings in a project together with European partner research institutions. The international platform JPI Oceans is funding the project.

CAPTION

Amphipods occur in high densities in the seabed of the North Sea

CREDIT

Alfred Wegener Institute / Sheng Wang

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JOURNAL

Environmental Pollution

DOI

10.1016/j.envpol.2022.119899 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Low-frequency noise pollution impairs burrowing activities of marine benthic invertebrates

ARTICLE PUBLICATION DATE

1-Oct-2022

LAUGHING GAS

Key mechanisms of airway relaxation in asthma revealed in new study

Novel role for nitric oxide in treatment of asthma and other obstructive airway diseases detailed by team at University Hospitals and Case Western Reserve University

Peer-Reviewed Publication

UNIVERSITY HOSPITALS CLEVELAND MEDICAL CENTER

CLEVELAND--Many therapeutics for asthma and other obstructive lung diseases target the β2-adrenergic receptor (β2AR), a G protein-coupled receptor (GPCR) that rapidly supports airway relaxation when stimulated. Yet, overuse of these agents is associated with adverse health outcomes, including death, which has limited their utility as frontline therapies.  

Now, a mouse model study published in today’s issue of Molecular Cell, from investigators at University Hospitals (UH) and Case Western Reserve University, identifies a novel strategy to isolate the beneficial effects of β2AR stimulation. This suggests a new therapeutic approach to airway diseases as well as numerous other conditions involving the aberrant function of GPCRs.

“Not only is the β2-adrenergic receptor the mainstay for keeping airways open, it's often studied as a prototype for how GPCRs work, which constitute the targets of 50% of all drugs,” explained Jonathan S. Stamler, MD, President, Harrington Discovery Institute at UH, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation, and Professor of Medicine and Biochemistry at UH and Case Western Reserve School of Medicine.

“Our discovery highlights an obvious benefit to asthma and it's exemplary of what to expect in GPCR regulation. It opens the area for broad-based research in maximizing the therapeutic benefits of GPCRs.”

All GPCRs, including the β2AR, operate via a feedback loop in which the same molecules that the receptors help generate can circle back and turn the receptors “off” or inactivate them. In the new study, the research team reveal nitric oxide to be a key molecule in the β2AR feedback loop, showing that the production of nitric oxide after β2AR stimulation mediates airway relaxation, but overproduction of the molecule also inactivates β2AR, leading to bronchoconstriction.

“If you prevent that feedback, you’re left with a very powerful airway relaxant that before now had not been thought to be that important in airway relaxation,” said Dr. Stamler.

The study also demonstrates that mice harboring a specific mutation in the β2AR gene that prevents nitric oxide from binding to and inactivating the receptor are resistant to bronchoconstriction, inflammation, and asthma.

Other GPCR receptors shown in the study to be regulated by nitric oxide-based protein modification include the β1 adrenergic receptor and the angiotensin II receptor 1.

“Nitric oxide should be thought of as a key new player in how this class of receptors works,” Dr. Stamler added. “It’s responsible for both the beneficial effects of the receptors and for turning them off. And if you can understand how they're being turned off--how that nitric oxide is popping on to the receptor--and you can block that, you're going to be left with a new pathway for opening airways. The next step in our research will focus on leveraging this new pathway therapeutically.”

###

Fonseca, F. V., Stamler, J.S., et al. S-nitrosylation is required for β2AR desensitization and experimental asthma. Molecular Cell (2022). DOI: 10.1016/j.molcel.2022.06.033.

About University Hospitals / Cleveland, Ohio
Founded in 1866, University Hospitals serves the needs of patients through an integrated network of more than 20 hospitals (including five joint ventures), more than 50 health centers and outpatient facilities, and over 200 physician offices in 16 counties throughout northern Ohio. The system’s flagship quaternary care, academic medical center, University Hospitals Cleveland Medical Center, is affiliated with Case Western Reserve University School of Medicine, Northeast Ohio Medical University, Oxford University and the Technion Israel Institute of Technology. The main campus also includes the UH Rainbow Babies & Children's Hospital, ranked among the top children’s hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, with more than 3,000 active clinical trials and research studies underway. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including “America’s Best Hospitals” from U.S. News & World Report. UH is also home to 19 Clinical Care Delivery and Research Institutes. UH is one of the largest employers in Northeast Ohio with more than 30,000 employees. Follow UH on LinkedIn, Facebook and Twitter. For more information, visit UHhospitals.org.

About Case Western Reserve University
Case Western Reserve University is one of the country's leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 5,800 undergraduate and 6,300 graduate students comprise our student body. Visit case.edu to see how Case Western Reserve thinks beyond the possible.

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JOURNAL

Molecular Cell

DOI

10.1016/j.molcel.2022.06.033 

Looking inside a neutron star – new model will improve insights gleaned from gravitational waves

Peer-Reviewed Publication

UNIVERSITY OF BIRMINGHAM

The unique oscillations in binary neutron stars right before they merge could have big implications for the insights scientists can glean from gravitational wave detection.

Researchers at the University of Birmingham have demonstrated the way in which these vibrations, caused by the interactions between the two stars’ tidal fields as they get close together, affect gravitational-wave observations. The study is published in Physical Review Letters.

Taking these movements into account could make a huge difference to our understanding of the data taken by the Advanced LIGO and Virgo instruments, set up to detect gravitational waves – ripples in time and space – produced by the merging of black holes and neutron stars.

The researchers aim to have a new model ready for Advanced LIGO’s next observing run and even more advanced models for the next generation of Advanced LIGO instruments, called A+, which are due to begin their first observing run in 2025.

Since the first gravitational waves were detected by the LIGO Scientific Collaboration and Virgo Collaboration in 2016, scientists have been focused on advancing their understanding of the massive collisions that produce these signals, including the physics of a neutron star at supra nuclear densities.

Dr Geraint Pratten, of the Institute for Gravitational Wave Astronomy at University of Birmingham, is lead-author on the paper. He said: “Scientists are now able to get lots of crucial information about neutron stars from the latest gravitational wave detections. Details such as the relationship between the star’s mass and its radius, for example, provide crucial insight into fundamental physics behind neutron stars. If we neglect these additional effects, our understanding of the structure of the neutron star as a whole can become deeply biased.”

Dr Patricia Schmidt, co-author on the paper and Associate Professor at the Institute for Gravitational Wave Astronomy, added: “These refinements are really important. Within single neutron stars we can start to understand what’s happening deep inside the star’s core, where matter exists at temperatures and densities we cannot produce in ground-based experiments. At this point we might start to see atoms interacting with each other in ways we have not yet seen – potentially requiring new laws of physics.”

The refinements devised by the team represent the latest contribution from the University of Birmingham to the Advanced LIGO programme. Researchers in the University’s Institute for Gravitational Wave Astronomy have been deeply involved in design and development of the detectors since the programme’s earliest stages. Looking ahead, PhD student Natalie Williams is already progressing work on calculations to further refine and calibrate the new models.

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JOURNAL

Physical Review Letters

DOI

10.1103/PhysRevLett.129.081102. 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Impact of dynamical tides on the reconstruction of the neutron star equation of state

Dentists should give antibiotics to high-risk patients to help prevent life-threatening heart infection

Current NICE guidelines, advising against routine use of antibiotics before invasive dental procedures for those at high IE-risk, should be reconsidered

Peer-Reviewed Publication

UNIVERSITY OF SHEFFIELD

●      University of Sheffield study finds that antibiotics reduce the risk of a life-threatening heart infection following invasive dental treatment - for high-risk patients

●      Infective endocarditis (IE) is an infection of the heart valves, that causes heart failure, strokes and other serious disabilities that result in a 30 per cent, first year death rate

●      A causal link between dental treatment and IE has long been suspected with 30 to 40 per cent of cases being caused by bacteria from the mouth, however this link has been questioned due to a lack of robust research. Until now there has also never been a study to demonstrate that antibiotics are effective in reducing the risk of IE

●      Guideline committees around the world, except in the UK, recommend antibiotics are given to people at high-risk of IE before undergoing invasive dental treatment to reduce the risk of developing IE

●      University of Sheffield research is the biggest ever study to examine the link between IE and dental treatment and for the first time confirms that giving antibiotics to those at high IE-risk before invasive dental procedures, significantly reduces the risk of them developing IE

People who are at high risk of developing a life-threatening heart infection should be given antibiotics before undergoing invasive dental procedures, according to new research from the University of Sheffield.

These results suggest that current NICE guidelines, advising against routine use of antibiotics before invasive dental procedures for those at high IE-risk, should be reconsidered.

The study, led by Professor Martin Thornhill from the University’s School of Clinical Dentistry, suggests that current UK guidelines against the use of antibiotics, issued by the National Institute for Health and Care Excellence (NICE), could be putting high-risk patients at unnecessary extra risk when undergoing invasive dental procedures.

At the same time, the results validate guidance in the USA, Europe and elsewhere that recommend that those at high-risk are given antibiotics before invasive dental procedures.

Professor Martin Thornhill, Professor of Translational Research in Dentistry at the University of Sheffield and lead author of the study, said: “Infective endocarditis is a rare but devastating heart infection in which around 30 per cent of people die within the first year of developing it. We know that 30-45 per cent of IE cases are caused by bacteria that derive from the mouth, but what has been unclear and disputed until now is whether there is a strong link between invasive dental procedures, such as tooth extractions, and IE in patients who are at high risk of developing the infection.

“Results from our study validate for the first time the guidance of the major guideline committees around the world, such as The American Heart Association and the European Society for Cardiology, which recommend that those at high IE risk should receive AP before undergoing invasive dental procedures. In contrast, our data suggests that current UK NICE guidance against the routine use of AP, could be putting high risk patients at unnecessary extra risk of developing IE, and should be reviewed in light of this new evidence.”

Published in the Journal of the American College of Cardiology, the research is the biggest ever study to examine the association between infective endocarditis (IE) - a life-threatening infection of the heart often caused by bacteria that derive from the mouth - and invasive dental procedures.

The study was performed in the USA where patients at high IE-risk (those with artificial or repaired heart valves, patients with certain congenital heart conditions or a previous history of IE) are recommended to receive antibiotics before invasive dental procedures - called antibiotic prophylaxis (AP) - to reduce their risk of developing IE.

The research is the first to demonstrate that AP reduces the risk of IE following invasive dental treatment for those at high-risk of developing the infection.

Since the 1950’s, guideline committees around the world have recommended that people at increased risk of IE should be given AP before undergoing invasive dental procedures. However, there has never been any robust research directly linking dental procedures with the development of IE or any study to demonstrate that AP is effective in reducing the risk of developing IE.

Due to this lack of evidence, concerns about the unnecessary use of antibiotics and the risk that AP could promote the development of antibiotic resistant bacteria, guideline committees have since reduced the number of people that AP is recommended for - recommending that only those at high risk for IE should receive AP before invasive dental procedures. In the UK, however, NICE went even further stating that “Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.”

The study from Sheffield analysed the medical history of nearly eight million people in the USA over a 16 month period, including 36,773 individuals at high-risk of IE. The researchers looked at whether the patients had invasive dental treatment, if they then went on to develop IE within 30 days and whether they had been given AP before the procedure.

Researchers found that 3,774 of those studied developed IE within 30 days of dental treatment. They also found that the risk of developing IE was 160 times greater in those at high IE-risk than in the general low-risk population.

The association between invasive dental procedures an IE was particularly strong for dental extractions and oral surgical procedures. For patients at high IE-risk, the risk of developing IE was one in every 250 extractions and one in every 100 oral surgery procedures without AP cover. The risk in the general low risk population was extremely small.

The study found however, that only 32.6 per cent of high IE-risk patients received AP before invasive dental procedures. This allowed the researchers to study the effectiveness of AP. They found that the risk of developing IE was nearly 10 times greater when dental extractions were performed in high-risk patients without AP cover than when performed with AP cover. Similarly, the risk of IE was 12.5 times greater when oral surgery procedures were performed in high-risk patients without AP cover than when performed with AP cover.

For the USA, even though the study’s results validate The American Heart Association guidance, the research found that compliance with this advice was low –only 32.6 per cent of those at high risk of IE were given AP before undergoing invasive dental procedures.

Professor Thornhill added: “It is reassuring for patients, cardiologists and dentists that our data validates the American, European and other guidelines from around the world that recommend that patients at high risk for IE should receive AP before invasive dental procedures. It is concerning, however, that compliance with this guidance by dentists in the USA was so low. Clearly, more needs to be done to improve compliance with the American Heart Association guidelines.”

The study, Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures, is published in the Journal of the American College of Cardiology. It was performed in the United States using data from IBM Health and was funded by Delta Dental of Michigan and Renaissance Health Service Corporation in the US. To access the paper, visit: https://doi.org/10.1016/j.jacc.2022.06.030 

Ends

 Media contact: Amy Huxtable, Media and PR Officer at the University of Sheffield, 07568116781 or a.l.huxtable@sheffield.ac.uk

 Dentistry at the University of Sheffield

The University of Sheffield

With almost 29,000 of the brightest students from over 140 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world’s leading universities.

A member of the UK’s prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines.

Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in.

Sheffield has six Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields.

Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, GlaxoSmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations.

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JOURNAL

Journal of the American College of Cardiology

DOI

10.1016/j.jacc.2022.06.030 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures

COVID OUT clinical trial suggests metformin effective at reducing odds of serious outcomes for COVID-19 patients seeking early treatment

Trial compared effect of ivermectin, fluvoxamine, and metformin in randomized double-blinded placebo- controlled trial

Peer-Reviewed Publication

UNIVERSITY OF MINNESOTA MEDICAL SCHOOL

 

VIDEO: DR. CAROLYN BRAMANTE FROM THE UNIVERSITY OF MINNESOTA ANSWERS QUESTIONS ABOUT COVID OUT. view more 

CREDIT: UNIVERSITY OF MINNESOTA MEDICAL SCHOOL

Published in the New England Journal of Medicine, researchers — led by the University of Minnesota Medical School and School of Public Health — have found that metformin, a commonly prescribed diabetes medication, lowers the odds of emergency department visits, hospitalizations, or death due to COVID-19 by over 40 percent; and over 50 percent if prescribed early in onset of symptoms. The study also found no positive effect from treatment with either ivermectin or low-dose fluvoxamine.

“We are pleased to contribute to the body of knowledge around COVID-19 therapies in general, with treatments that are widely available,” said Carolyn Bramante, MD, principal investigator of the study and an assistant professor of internal medicine and pediatrics at the U of M Medical School. “Our trial suggests that metformin may reduce the likelihood of needing to go to the emergency room or be hospitalized for COVID-19.”

Bramante noted that this was a secondary outcome of the trial; the primary outcome included whether someone had low oxygen on a home oxygen monitor, and none of the medications in the trial prevented the primary outcome.

The COVID-OUT trial was the nation’s first to study whether metformin, a medication for type 2 diabetes; low-dose fluvoxamine, an antidepressant; and ivermectin, an antiparasitic, or their combinations could serve as possible treatments to prevent ER visits or hospitalization, as well as Long-COVID.

The study design was simple — patients were randomly assigned to receive one of the three drugs individually, placebo, or a combination of metformin and fluvoxamine or metformin and ivermectin. Although the study was placebo-controlled with exact-matching placebo pills, Dr. Bramante says 83% of volunteers received medications supported by existing data because of the six-arm design. Each participant received 2 types of pills to keep their treatment assignment masked, for 3 to 14 days of treatment. Each volunteer tracked their symptoms, and after 14 days, they completed a survey.

The 1323 participants in the trial were limited to adults with a body mass index greater than or equal to 25 kg/m2, which qualifies as overweight – for instance, someone who was at least five feet and six inches tall and weighed more than 155 pounds. To qualify for the study, volunteers enrolled within three days after receiving a positive COVID-19 test. It was among the first randomized clinical trials for COVID-19 to include pregnant women.

The study included those who were vaccinated and those who were not. This is the first published trial where the majority of participants were vaccinated. 

“Although we know COVID-19 vaccines are highly effective, we know that some new strains of the virus may evade immunity and vaccines may not be available worldwide. So we felt we should study safe, available and inexpensive outpatient treatment options as soon as possible,” said Bramante. “Understanding whether outpatient treatments could ensure more people survive the illness if they contract it and have fewer long-term symptoms is an important piece of the pandemic response.”

The clinical trial launched in January 2021 after U of M Medical School researchers identified, through computer modeling and observational studies, that outpatient metformin use appeared to decrease the likelihood of mortality from, or being hospitalized for COVID-19. Their research, in partnership with UnitedHealth Group, was published in the Journal of Medical Virology and in The Lancet Healthy Longevity. Test-tube studies also found that metformin inhibited the Covid-19 virus in lab settings. These findings, along with additional prospective studies supporting the use of higher-dose fluvoxamine and ivermectin, provided the evidence to include all three medications as well as combination arms.

“Observational studies and in vitro experiments cannot be conclusive but do contribute to bodies of evidence,” said Bramante, who is also an internist and pediatrician with M Health Fairview. “To complete this study, we enrolled volunteers nationwide through six institutions in the U.S., including in Minneapolis.”

Participating clinical trial sites included M Health Fairview and Hennepin Healthcare in Minneapolis, Northwestern University in Chicago, Olive View – UCLA Education & Research Institute in Los Angeles, Optum in Colorado and Indiana, and University of Colorado Denver. Co-investigators on the study include Jared Huling, PhD; Thomas Murray, PhD; Hrishikesh Belani, MD; Michelle Biros, MD; David Boulware, MD; David Leibovitz, MD; Jacinda Nicklas, MD; David Odde, PhD; Matt Pullen, MD; Mike Puskarich, MD; John Buse, MD, PhD; Jennifer Thompson, MD; and Christopher Tignanelli, MD.

The trial received monetary support from the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants, and UnitedHealth Group.

In addition, this research was supported by the National Institutes of Health’s National Center for Advancing Translational Sciences, grants UL1TR002494 and KL2TR002492, and the National Institute of Digestive, Diabetes, and Kidney diseases K23 DK124654. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.

 

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JOURNAL

New England Journal of Medicine

DOI

10.1056/NEJMoa2201662 

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Randomized trial of metformin, ivermectin, and fluvoxamine for Covid-19

Metformin drastically reduces COVID hospitalization, study shows

Widely available drug reduced emergency room visits, hospitalization, and death by COVID-19 by more than half if started within 4 days of symptoms

Peer-Reviewed Publication

PARSEMUS FOUNDATION

The widely available diabetes drug metformin reduced serious outcomes by more than half if started within 4 days of COVID symptoms in a large, randomized, double blind controlled trial, the University of Minnesota announced today. The results were published Aug. 18 in the New England Journal of Medicine.

The study was primarily funded by three philanthropic foundations: Parsemus Foundation, Rainwater Charitable Foundation, and Fast Grants.

“This was really intriguing to us early on when we learned that people who take metformin were catching COVID less and being hospitalized less,” said Elaine Lissner, founder and trustee of small California nonprofit Parsemus Foundation, which works on low-cost solutions neglected by the pharmaceutical industry. “But you don’t know whether it’s just coincidence until you start at the beginning, with a rigorous randomized trial.”

“When we learned that researchers at the University of Minnesota were already trying to raise funds to test it, we jumped at the opportunity.”

A little-known past

Metformin, also known as Glucophage, has an added benefit: a little-known past in the 1950s as an anti-viral called “Fluamine.” In more recent research, it also seems to affect mTOR inflammation pathways. Since COVID involves viral inflammation, lead researcher Dr. Carolyn Bramante and team thought the combination of anti-inflammatory plus antiviral action was intriguing enough to put to the test.

The study almost didn’t happen, though. At the time, most government and pharmaceutical funds were going to vaccine research, or the search for profitable new drugs.

“We took a chance and gave what we could, enough to get the first few study sites started and generate preliminary data to strengthen the case for other funders,” said Linda Brent, executive director of the Parsemus Foundation. “But the study never would have made it if it weren’t for the dedicated larger funders who believed in it right away and came on board with critical support.”

Three medications studied

For added rigor, the large University of Minnesota study compared three medications that were considered promising at the time—fluvoxamine, an antidepressant that had shown strong results in previous studies; ivermectin, the object of much interest and passion; and metformin — and provided valuable answers, even about the drugs that were not the clear winner.

“You can argue about details, but in the end, this was kind of ‘three strikes and you’re out’ for ivermectin,” said Lissner. “But ivermectin deserved this kind of careful study, head-to-head with other medications, to finally get solid answers. You have to give everything a fair test.”

“And I think a lot of us were pretty disappointed that the fluvoxamine results were not conclusive. We did learn that the dose the study used, which was a third to half as much as used in previous studies in an attempt to avoid side effects, was not enough to make a significant difference. I don’t think the door is closed on fluvoxamine at higher doses, though.”

“But in the end,” added Lissner, “you have to accept what the science tells you, no matter which you were rooting for. And it’s probably better this way. Metformin is an incredibly common drug, taken by millions of people all over the world. There’s no stigma like with an antidepressant, and it’s a lot easier to take than the other two.”

In 2019, metformin was the fourth-most commonly prescribed medication in the United States, with more than 85 million prescriptions written for over 17 million patients. FDA guidelines indicate that it should not be taken by people with advanced kidney disease, and should be taken with food, or in extended-release formulation, to avoid stomach upset. Side effects are minor and include loose stools. Metformin is also considered safe for use in pregnant women.

The study included 1323 participants most at risk of serious outcomes—adults over 30 and with BMI over 25 kg/m2—to get lifesaving results more quickly. Future studies could include lower-risk participants. However, studies of metformin for other indications, such as the national TAME trial by the American Federation for Aging Research, remain unfunded.

“I think there are lessons for all of us in making sure our global clinical trial systems are more robust and ready to jump in on globally critical studies like this in the future,” emphasized Lissner. “It shouldn’t be little foundations like us funding studies of global importance. In the meantime, I hope all the hard work and late nights pay off, and clinicians around the world take notice: metformin, an exceedingly inexpensive drug they prescribe every day, if given to high-risk people with COVID right away, can reduce serious outcomes by more than half.”

Details about the study results were published online August 18 in the New England Journal of Medicine and can be found in the University of Minnesota’s COVID-OUT study press release.

About the Parsemus Foundation (San Francisco): The Parsemus Foundation works to create meaningful improvements in human and animal health and welfare by advancing innovative and neglected medical research. The foundation’s focus is on supporting proof-of-concept studies and then pursuing press coverage of the results, so that the advances change treatment practice rather than disappearing into the scientific literature. As a small, agile nonprofit organization, the Parsemus Foundation was able to pivot from its regularly funded programs to a new focus on COVID-19 treatment during the pandemic. More information on the Parsemus Foundation and the work presented here can be found at: https://www.parsemus.org/humanhealth/covid-19/

 

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JOURNAL

New England Journal of Medicine

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19