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Fast, portable test can diagnose COVID-19 and track variants

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The field test, called NIRVANA, can simultaneously detect and sequence SARS-CoV-2, influenza and other viruses

LA JOLLA–(March 31, 2021) Clinicians using a new viral screening test can not only diagnose COVID-19 in a matter of minutes with a portable, pocket-sized machine, but can also simultaneously test for other viruses–like influenza–that might be mistaken for the coronavirus. At the same time, they can sequence the virus, providing valuable information on the spread of COVID-19 mutations and variants. The new test, dubbed NIRVANA, was described online today by a multi-institution team of scientists in the journal Med.

“This is a virus detection and surveillance method that doesn’t require an expensive infrastructure like other approaches,” says Juan Carlos Izpisua Belmonte, co-corresponding author and a professor in Salk’s Gene Expression Laboratory. “We can accomplish with one portable test the same thing that others are using two or three different tests, with different machines, to do.”

Around the world, more than 100 million people have been infected with SARS-CoV-2, the virus that causes COVID-19. A staggering 500,000 Americans have died from COVID-19 to date. Testing the population is key to stopping the spread of the virus. In addition, tracking the spread of new SARS-CoV-2 variants–some of which could respond differently to treatments or vaccines–is critical.

Today, the standard approach to determining whether a nasal swab is positive for COVID-19 is to run a polymerase chain reaction (PCR) test to detect genetic material from the SARS-CoV-2 virus. If the sample is negative, however, patients and clinicians don’t get any information on what might be causing the coronavirus-like symptoms–unless they run separate PCR tests, using different swab samples, for other viruses. And if the sample is positive for SARS-CoV-2, they don’t learn which COVID-19 variant a patient is infected with unless another set of tests is run; those require a large and expensive next-generation gene-sequencing machine.

Last summer, Mo Li, an assistant professor of bioscience at King Abdullah University of Science and Technology in Saudi Arabia, was pondering ways he could lend his expertise in genetic engineering and nanopore sequencing to combatting the COVID-19 pandemic. Li, who previously spent six years as a Salk postdoctoral researcher in the Izpisua Belmonte lab, wondered whether a gene-detection approach called isothermal recombinase polymerase amplification (RPA) coupled with real-time nanopore sequencing might be more useful–and faster, cheaper and more portable–than the current COVID-19 testing approach. He teamed up with Izpisua Belmonte to find out.

Unlike PCR, which cycles through lower and higher temperatures to separate DNA strands and copy them, RPA uses proteins–rather than temperature changes–to accomplish the same thing in only 20 minutes. The technology lets researchers copy longer stretches of DNA, and probe for multiple genes at the same time.

“We quickly realized that we could use this technique to not only detect SARS-CoV-2, but other viruses at the same time,” says Li.

In the new paper, Li and Izpisua Belmonte describe a small, portable device that can screen 96 samples at the same time using the RPA assay. They call the method NIRVANA, for “nanopore sequencing of isothermal rapid viral amplification for near real-time analysis.”

The scientists designed NIRVANA to simultaneously test samples for COVID-19, influenza A, human adenovirus, and non-SARS-CoV-2 human coronavirus. In just 15 minutes, the researchers report, the device begins to report positive and negative results. And within three hours, the device finalizes results on all 96 samples–including the sequences of five regions of SARS-CoV-2 that are particularly prone to accumulate mutations leading to new variants such as the B.1.1.7 variant identified in the UK.

Li and Izpisua Belmonte tested NIRVANA on 10 samples known to be positive for SARS-CoV-2, 60 samples of unknown SARS-CoV-2 status, as well as samples of municipal wastewater harboring the SARS-COV-2 virus and others. In all cases, the assay was able to correctly identify which viruses were present. The sequencing data also allowed them to narrow down the origin of SARS-CoV-2 in positive samples; differentiating strains from China and Europe, for instance.

“The design of this assay is really flexible, so it’s not just limited to the examples we’ve shown,” says Li. “We can easily adapt it to tackle another pathogen, even something new and emergent.”

With the small size and portability of the NIRVANA workflow, it could be used for fast virus detection at schools, airports or ports, the researchers say. It also could be used to monitor wastewater or streams for the presence of new viruses.

“The pandemic has provided two important lessons: first, test widely and quickly, and second, know your variants. Our NIRVANA method provides a promising solution to these two challenges not only for the current pandemic but also for possible future ones,” says Izpisua Belmonte, who holds the Roger Guillemin Chair at Salk. Market analysis would be required to determine whether the initial cost of commercialization–and the constant tweaks to the test needed to make sure it detected new variants or new viruses of interest–are worth it, Belmonte adds.

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In addition to Izpisua Belmonte and Li, other authors on the study were Concepcion Rodriguez Esteban of Salk; Chongwei Bi, Gerargo Ramos-Mandujano, Sharis Hala, Jinna Xu, Sara Mfarrej, Yeteng Tian and Arnab Pain of King Abdullah University of Science and Technology (KAUST); Estrella Nunez Delicado of UCAM Universidad Católica San Antonio de Murcia; Fadwa Alofi of King Fahad Hospital; Asim Khogeer of Saudi Arabia’s Ministry of Health; Anwar Hashem of King Abdulaziz University; and Naif Almontashiri of Taibah University.

The work described in the current paper was supported by a competitive research grant from the King Abdullah University of Science and Technology.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk’s mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer’s, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

https://www.salk.edu/news-release/fast-portable-test-can-diagnose-covid-19-and-track-variants/

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Scientists find molecular patterns that may help identify extraterrestrial life

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Upcoming Solar System exploration missions will search for extraterrestrial (ET) life, but ET life may not be like Earth life; a new mass spectrometry analysis technique may allow for process-based ways to find ET life that is compositionally alien

Scientists have begun the search for extraterrestrial life in the Solar System in earnest, but such life may be subtly or profoundly different from Earth-life, and methods based on detecting particular molecules as biosignatures may not apply to life with a different evolutionary history. A new study by a joint Japan/US-based team, led by researchers at the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology, has developed a machine learning technique which assesses complex organic mixtures using mass spectrometry to reliably classify them as biological or abiological.

In season 1, episode 29 (“Operation: Annihilate!”) of Star Trek, which aired in 1966, the human-Vulcan hybrid character Spock made the observation “It is not life as we know or understand it. Yet it is obviously alive; it exists.” This now 55-year old pop-culture meme still makes a point: how can we detect life if we fundamentally don’t know what life is, and if that life is really different from life as we know it?

The question of “Are we alone?” as living beings in the Universe has fascinated humanity for centuries, and humankind has been looking for ET life in the Solar System since NASA’s Viking 2 mission to Mars in 1976. There are presently numerous ways scientists are searching for ET life. These include listening for radio signals from advanced civilisations in deep space, looking for subtle differences in the atmospheric composition of planets around other stars, and directly trying to measure it in soil and ice samples they can collect using spacecraft in our own Solar System. This last category allows them to bring their most advanced chemical analytical instrumentation directly to bear on ET samples, and perhaps even bring some of the samples back to Earth, where they can be carefully scrutinised.

Exciting missions such as NASA’s Perseverance rover will look for life this year on Mars; NASA’s Europa Clipper, launching in 2024, will try to sample ice ejected from Jupiter’s moon Europa, and its Dragonfly mission will attempt to land an “octacopter” on Saturn’s moon Titan starting in 2027. These missions will all attempt to answer the question of whether we are alone.

Mass spectrometry (MS) is a principal technique that scientists will rely on in spacecraft-based searches for ET life. MS has the advantage that it can simultaneously measure multitudes of compounds present in samples, and thus provide a sort of “fingerprint” of the composition of the sample. Nevertheless, interpreting those fingerprints may be tricky.

As best as scientists can tell, all life on Earth is based on the same highly coordinated molecular principles, which gives scientists confidence that all Earth-life is derived from a common ancient terrestrial ancestor. However, in simulations of the primitive processes that scientists believe may have contributed to life’s origins on Earth, many similar but slightly different versions of the particular molecules terrestrial life uses are often detected. Furthermore, naturally occurring chemical processes are also able to produce many of the building blocks of biological molecules. Since we still have no known sample of alien life, this leaves scientists with a conceptual paradox: did Earth-life make some arbitrary choices early in evolution which got locked in, and thus life could be constructed otherwise, or should we expect that all life everywhere is constrained to be exactly the same way it is on Earth? How can we know that the detection of a particular molecule type is indicative of whether it was or was not produced by ET life?

It has long troubled scientists that biases in how we think life should be detectable, which are largely based on how Earth-life is presently, might cause our detection methods to fail. Viking 2 in fact returned odd results from Mars in 1976. Some of the tests it conducted gave signals considered positive for life, but the MS measurements provided no evidence for life as we know it. More recent MS data from NASA’s Mars Curiosity rover suggest there are organic compounds on Mars, but they still do not provide evidence for life. A related problem has plagued scientists attempting to detect the earliest evidence for life on Earth: how can we tell if signals detected in ancient terrestrial samples are from the original living organisms preserved in those samples or derived from contamination from the organisms which presently pervade our planet?

Scientists at the Earth-Life Science Institute at the Tokyo Institute of Technology in Japan and the National High Magnetic Field Laboratory (The National MagLab) in the US decided to address this problem using a combined experimental and machine learning computational approach. The National MagLab is supported by the US National Science Foundation through NSF/ DMR-1644779 and the State of Florida to provide cutting-edge technologies for research. Using ultrahigh-resolution MS (a technique known as Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry (or FT-ICR MS)) they measured the mass spectra of a wide variety of complex organic mixtures, including those derived from abiological samples made in the lab (which they are fairly certain are not living), organic mixtures found in meteorites (which are ~ 4.5 billion-year-old samples of abiologically produced organic compounds which appear to have never become living), laboratory-grown microorganisms (which fit all the modern criteria of being living, including novel microbial organisms isolated and cultured by ELSI co-author Tomohiro Mochizuki), and unprocessed petroleum (or raw natural crude oil, the kind we pump out of the ground and process into gasoline, which is derived from organisms which lived long ago on Earth, providing an example of how the “fingerprint” of known living organisms might change over geological time). These samples each contained tens of thousands of discrete molecular compounds, which provided a large set of MS spectra that could be compared and classified.

In contrast to approaches that use the accuracy of MS measurements to uniquely identify each peak with a particular molecule in a complex organic mixture, the researchers instead aggregated their data and looked at the broad statistics and distribution of signals. Complex organic mixtures, such as those derived from living things, petroleum, and abiological samples present very different “fingerprints” when viewed in this way. Such patterns are much more difficult for a human to detect than the presence or absence of individual molecule types.

The researchers fed their raw data into a computer machine learning algorithm and surprisingly found that the algorithms were able to accurately classify the samples as living or non-living with ~95% accuracy. Importantly, they did so after simplifying the raw data considerably, making it plausible that lower-precision instruments, spacecraft-based instruments are often low power, could obtain data of sufficient resolution to enable the biological classification accuracy the team obtained.

The underlying reasons this classification accuracy is possible to remain to be explored, but the team suggests it is because of the ways biological processes, which modify organic compounds differently than abiological processes, relate to the processes which enable life to propagate itself. Living processes have to make copies of themselves, while abiological processes have no internal process controlling this.

“This work opens many exciting avenues for using ultra-high resolution mass spectrometry for astrobiological applications,” says co-author Huan Chen of the US National MagLab.

Lead author Nicholas Guttenberg adds, “While it is difficult if not impossible to characterise every peak in a complex chemical mixture, the broad distribution of components can contain patterns and relationships which are informative about the process by which that mixture came about or developed. If we’re going to understand complex prebiotic chemistry, we need ways of thinking in terms of these broad patterns – how they come about, what they imply, and how they change – rather than the presence or absence of individual molecules. This paper is an initial investigation into the feasibility and methods of characterisation at that level and shows that even discarding high-precision mass measurements, there is significant information in peak distribution that can be used to identify samples by the type of process that produced them.”

Co-author Jim Cleaves of ELSI adds, “This sort of relational analysis may offer broad advantages for searching for life in the Solar System, and perhaps even in laboratory experiments designed to recreate the origins of life.” The team plans to follow up with further studies to understand exactly what aspects of this type of data analysis allows for such successful classification.

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Reference:

Nicholas Guttenberg1,2,3, Huan Chen4, Tomohiro Mochizuki1, H. James Cleaves II1,5,6,*, Classification of the Biogenicity of Complex Organic Mixtures for the Detection of Extraterrestrial Life, Life, DOI: 10.3390/life11030234

1. Earth-Life Science Institute, Tokyo Institute of Technology, Ookayama, Tokyo 152-8550, Japan

2. Cross Labs, Cross Compass Ltd., 2-9-11-9F Shinkawa, Chuo-ku, Tokyo 104-0033, Japan

3. GoodAI, Na Petynce 213/23b, 169 00 Prague, Czech Republic

4. National High Magnetic Field Laboratory, Florida State University, 1800 East Paul Dirac Drive,
Tallahassee, FL 32310-4005, USA

5. Institute for Advanced Study, 1 Einstein Drive, Princeton, NJ 08540, USA

6. Blue Marble Space Institute of Science, Seattle, WA 98104, USA

More information:

Tokyo Institute of Technology (Tokyo Tech) stands at the forefront of research and higher education as the leading university for science and technology in Japan. Tokyo Tech researchers excel in fields ranging from materials science to biology, computer science, and physics. Founded in 1881, Tokyo Tech hosts over 10,000 undergraduate and graduate students per year, who develop into scientific leaders and some of the most sought-after engineers in industry. Embodying the Japanese philosophy of “monotsukuri,” meaning “technical ingenuity and innovation,” the Tokyo Tech community strives to contribute to society through high-impact research.

The Earth-Life Science Institute (ELSI) is one of Japan’s ambitious World Premiere International research centers, whose aim is to achieve progress in broadly inter-disciplinary scientific areas by inspiring the world’s greatest minds to come to Japan and collaborate on the most challenging scientific problems. ELSI’s primary aim is to address the origin and co-evolution of the Earth and life.

The World Premier International Research Center Initiative (WPI) was launched in 2007 by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to help build globally visible research centers in Japan. These institutes promote high research standards and outstanding research environments that attract frontline researchers from around the world. These centers are highly autonomous, allowing them to revolutionise conventional modes of research operation and administration in Japan.

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Source: https://bioengineer.org/scientists-find-molecular-patterns-that-may-help-identify-extraterrestrial-life/

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Life may have become cellular by using unusual molecules

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All modern life is cellular, but how life came to be cellular remains uncertain. New research suggests chemical compounds likely common on primitive Earth may have helped scaffold the emergence of biological cellularity.

Credit: Tony Z. Jia

All modern life is composed of cells, from single-celled bacteria to more complex organisms such as humans, which may contain billions or even trillions of cells, but how life came to be cellular remains uncertain. New research led by specially appointed assistant professor Tony Z. Jia at the Earth-Life Science Institute (ELSI) at Tokyo Institute of Technology, along with colleagues from around the world (Japan, Malaysia, France, Czech Republic, India and the USA), shows that simple chemical compounds known as hydroxy acids, which were likely common on primitive Earth, spontaneously link together and form structures reminiscent of modern cells when dried from solution, as may have happened on or in ancient beaches or puddles. The resulting structures may have helped scaffold the emergence of biological cellularity, and offer scientists a new avenue for studying early proto-biological evolution and the origins of life itself.

Modern cells are very complex, precisely organized assemblages of millions of molecules oriented in precise ways which help traffic materials into and out of cells in a highly coordinated fashion. As an analogy, a city is not just a random collection of buildings, streets and stoplights; rather, in an optimized city, the streets are arranged to allow for easy access to the buildings, and traffic flow is controlled to make the entire system function efficiently. As much as cities are the result of a historical and evolutionary process when primitive roving bands of humans settled down to work together in larger groups, cells are likely the result of similar processes by which simple molecules began to cooperate to form synchronized molecular systems.

How cellularization emerged is a long-standing scientific problem, and scientists are trying to understand how simple molecules can form the boundary structures which could have defined the borders of primitive cells. The boundaries of modern cells are typically composed of lipids, which are themselves composed of molecules which have the molecularly unusual property of spontaneously forming bounded structures in water known as vesicles. Vesicles form from simple molecules known as “amphiphiles,” a word derived from the Greek meaning “loving both” to reflect that such molecules have propensity to self-organize with water as well as with themselves. This molecular dance causes these molecules to orient themselves such that one part of these molecules preferentially aligns with the water they are dissolved in and another portion of these molecules tend to align with one another. This kind of self-organizational phenomenon is observed when groups of people enter elevators: rather than everyone facing in random directions, for various reasons people in elevators tend to all align themselves to face the elevator door. In the experiments investigated by Jia and colleagues, the low molecular weight hydroxy acid molecules, upon joining together become a new type of polymer (that could be similar in nature to amphiphiles), form droplets, rather than the bag-like structures biological lipids do.

Modern cell boundaries, or membranes as they are called, are primarily composed of a few types of amphiphilic molecules, but scientists suspect the property of forming a membrane is a more general property of many types of molecules. As much as modern cities likely adapted roads, buildings and traffic controls to deal with the subsequent problems of handling foot traffic, horse traffic and automobile traffic, primitive cells may have also slowly changed their composition and function to adapt to changes in the way other biological functions evolved. This new work offers insights into the problems primitive emergent biological systems may have had tom adapt to.

The types of molecules that help modern cells form their boundaries are only a small subset of the types which could allow for this kind of spontaneous self-assembly behavior. Previously, Jia and colleagues showed that hydroxy acids can be easily joined together to form larger molecules with emergent amphiphilic and self-assembly properties. They show in their new work that the subtle addition of one more type of subtly different hydroxy acid, in this case one bearing a positive electric charge, to the starting pool of reactants can result in new types of polyesters that spontaneously self-assemble into still more unexpected types of cell-like structures and lends them new functions which may help explain the origins of biological cellularity.

The novel structures Jia and coworkers prepared show emergent functions such as the ability to segregate nucleic acids, which are essential for conveying heredity in modern cells, or the ability to emit fluorescent light. That such minor changes in chemical complexity can result in major functional changes is significant. Jia and colleagues suggest that by further increasing the chemical complexity of their experimental system, still further emergent functions could arise among the resulting primitive compartments that could lead to greater understanding of the rise of the first cells.

Jia notes that this work is not merely theoretical nor even just relevant to basic science research. Major COVID vaccines such as those devised by Moderna and Pfizer involve the dispersion of RNA molecules in metabolizable lipid droplets; the systems Jia and coworkers have developed could be similarly biodegradable in vivo, and thus polyester droplets similar to the ones they prepared could be useful for similar drug delivery applications.

###

Reference:

Tony Z. Jia1,4*, Niraja V. Bapat1,2, Ajay Verma2, Irena Mamajanov1, H. James Cleaves II1,3,4, Kuhan Chandru5,6*, Incorporation of Basic α-Hydroxy Acid Residues into Primitive Polyester Microdroplets for RNA Segregation, Biomacromolecules, DOI: 10.1021/acs.biomac.0c01697

1. Earth-Life Science Institute, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8550, Japan

2. Department of Biology, Indian Institute of Science Education and Research, Pune, Maharashtra 411008, India

3. Institute for Advanced Study, 1 Einstein Drive, Princeton, New Jersey 08540, United States

4. Blue Marble Space Institute of Science, Seattle, Washington 98154, United States

5. Department of Physical Chemistry, University of Chemistry and Technology, Prague, Technicka 5, 16628 Prague 6 — Dejvice, Czech Republic

6. Space Science Centre (ANGKASA), Institute of Climate Change, National University of Malaysia, UKM, Bangi, Selangor Darul Ehsan 43650, Malaysia

More information:

Tokyo Institute of Technology (Tokyo Tech) stands at the forefront of research and higher education as the leading university for science and technology in Japan. Tokyo Tech researchers excel in fields ranging from materials science to biology, computer science, and physics. Founded in 1881, Tokyo Tech hosts over 10,000 undergraduate and graduate students per year, who develop into scientific leaders and some of the most sought-after engineers in industry. Embodying the Japanese philosophy of “monotsukuri,” meaning “technical ingenuity and innovation,” the Tokyo Tech community strives to contribute to society through high-impact research.

The Earth-Life Science Institute (ELSI) is one of Japan’s ambitious World Premiere International research centers, whose aim is to achieve progress in broadly inter-disciplinary scientific areas by inspiring the world’s greatest minds to come to Japan and collaborate on the most challenging scientific problems. ELSI’s primary aim is to address the origin and co-evolution of the Earth and life.

The World Premier International Research Center Initiative (WPI) was launched in 2007 by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to help build globally visible research centers in Japan. These institutes promote high research standards and outstanding research environments that attract frontline researchers from around the world. These centers are highly autonomous, allowing them to revolutionize conventional modes of research operation and administration in Japan.

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Source: https://bioengineer.org/life-may-have-become-cellular-by-using-unusual-molecules/

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No lasting benefit to tubes over antibiotics for childhood ear infections

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PITTSBURGH, May 12, 2021 – There is no long-term benefit to surgically placing tympanostomy tubes in a young child’s ears to reduce the rate of recurrent ear infections during the ensuing two years compared with giving oral antibiotics to treat ear infections, a randomized trial led by UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh pediatrician-scientists determined.

The trial results, published today in the New England Journal of Medicine, are among the first since the pneumococcal vaccine was added to pediatric vaccination schedules, providing updated evidence that may help shape pediatric guidelines on treating recurrent ear infections. Importantly, despite their greater use of antibiotics, the trial found no evidence of increased bacterial resistance among children in the medical-management group.

“Subjecting a young child to the risks of anesthesia and surgery, the possible development of structural changes of the tympanic membrane, blockage of the tube or persistent drainage through the tube for recurrent ear infections, which ordinarily occur less frequently as the child ages, is not something I would recommend in most instances,” said lead author Alejandro Hoberman, M.D., director of the Division of General Academic Pediatrics at UPMC Children’s Hospital and the Jack L. Paradise Endowed Professor of Pediatric Research at Pitt’s School of Medicine.

“We used to often recommend tubes to reduce the rate of ear infections, but in our study, episodic antibiotic treatment worked just as well for most children,” he said. “Another theoretical reason to resort to tubes is to use topical ear drops rather than systemic oral antibiotics in subsequent infections in the hope of preventing the development of bacterial resistance, but in this trial, we did not find increased resistance with oral antibiotic use. So, for most children with recurrent ear infections, why undergo the risks, cost and nuisance of surgery?”

Next to the common cold, ear infections are the most frequently diagnosed illness in U.S. children. Ear infections can be painful, force lost time at work and school, and may cause hearing loss. Tympanostomy tube placement, which is a surgical procedure to insert tiny tubes into a child’s eardrums to prevent the accumulation of fluid, is the most common operation performed on children after the newborn period.

Hoberman and his team enrolled 250 children ages 6 to 35 months of age at UPMC Children’s Hospital, Children’s National Medical Center in Washington, D.C., and Kentucky Pediatric and Adult Research in Bardstown, Ky. All of the children had had medically verified recurrent ear infections and had received the pneumococcal conjugate vaccine. They were randomly assigned to receive “medical management,” which involved receiving oral antibiotics at the time of ear infections, or the surgical insertion of tubes and antibiotic ear drops. The children were followed for two years.

Overall, there were no differences between children in the two groups when it came to the rate or severity of ear infections. And, though the children in the medical management group received more antibiotics, there also was no evidence of increased antimicrobial resistance in samples taken from the children. The trial also didn’t find any difference between the two groups in the children’s quality of life or in the effect of the children’s illness on parents’ quality of life.

One short-term benefit of placing tympanostomy tubes was that, on average, it took about two months longer for a child to develop a first ear infection after tubes were placed, compared with children whose ear infections were managed with antibiotics.

Another finding of the trial was that the rate of ear infections among children in both groups fell with increasing age. The rate of infections was 2.6 times higher in children younger than 1 year, compared with the oldest children in the trial, those between 2 and 3 years, regardless of whether they received medical management or tube insertion.

“Most children outgrow ear infections as the Eustachian tube, which connects the middle-ear with the back of the throat, works better,” Hoberman said. “Previous studies of tubes were conducted before children were universally immunized with pneumococcal conjugate vaccine, which also has reduced the likelihood of recurrent ear infections. It’s important to recognize that most children outgrow ear infections as they grow older. However, we must appreciate that for the relatively few children who continue to meet criteria for recurrent ear infections–three in six months or four in one year–after having met those criteria initially, placement of tympanostomy tubes may well be beneficial.”

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Additional study authors are Diego Preciado, M.D., Ph.D., and Daniel E. Felton, M.D., both of Children’s National Medical Center; Jack L. Paradise, M.D., David H. Chi, M.D., MaryAnn Haralam, M.S.N., C.R.N.P., Diana H. Kearney, R.N., C.C.R.C., Sonika Bhatnagar, M.D., M.P.H., Gysella B. Muñiz Pujalt, M.D., Timothy R. Shope, M.D., M.P.H., Judith M. Martin, M.D., Marcia Kurs-Lasky, M.S., Hui Liu, M.S., Kristin Yahner, M.S., Jong-Hyeon Jeong, Ph.D., Jennifer P. Nagg, R.N., Joseph E. Dohar, M.D., and Nader Shaikh, M.D., M.P.H., all of Pitt; Norman L. Cohen, M.D., and Brian Czervionke, M.D., both of UPMC Children’s Community Pediatrics; and Stan L. Block, M.D., of Kentucky Pediatric and Adult Research.

This research was funded by National Institute on Deafness and Other Communication Disorders grant NCT02567825.

To read this release online or share it, visit http://www.upmc.com/media/news/051221-Hoberman-Ear-Tubes-NEJM [when embargo lifts].

About the University of Pittsburgh School of Medicine

As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.

About UPMC Children’s Hospital of Pittsburgh

Regionally, nationally, and globally, UPMC Children’s Hospital of Pittsburgh is a leader in the treatment of childhood conditions and diseases, a pioneer in the development of new and improved therapies, and a top educator of the next generation of pediatricians and pediatric subspecialists. With generous community support, UPMC Children’s Hospital has fulfilled this mission since its founding in 1890. UPMC Children’s is recognized consistently for its clinical, research, educational, and advocacy-related accomplishments, including ranking in the top 10 on the 2020-2021 U.S. News & World Report Honor Roll of America’s Best Children’s Hospitals. UPMC Children’s also ranks 15th among children’s hospitals and schools of medicine in funding for pediatric research provided by the National Institutes of Health (FY2019).

http://www.upmc.com/media

Contact: Allison Hydzik

Office: 412-647-9975

Mobile: 412-559-2431

E-mail: [email protected]

Contact: Andrea Kunicky

Mobile: 412-552-7448

E-mail: [email protected]

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Source: https://bioengineer.org/no-lasting-benefit-to-tubes-over-antibiotics-for-childhood-ear-infections/

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Research reveals ancient people had more diverse gut microorganisms

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MISSOULA – Only an anthropologist would treasure millennia-old human feces found in dry caves.

Just ask Dr. Meradeth Snow, a University of Montana researcher and co-chair of UM’s Department of Anthropology. She is part of an international team, led by the Harvard Medical School-affiliated Joslin Diabetes Center, that used human “paleofeces” to discover that ancient people had far different microorganisms living in their guts than we do in modern times.

Snow said studying the gut microbes found in the ancient fecal material may offer clues to combat diseases like diabetes that afflict people living in today’s industrialized societies.

“We need to have some specific microorganisms in the right ratios for our bodies to operate effectively,” Snow said. “It’s a symbiotic relationship. But when we study people today – anywhere on the planet – we know that their gut microbiomes have been influenced by our modern world, either through diet, chemicals, antibiotics or a host of other things. So understanding what the gut microbiome looked like before industrialization happened helps us understand what’s different in today’s guts.”

This new research was published May 12 in the prestigious journal Nature. The article is titled “Reconstruction of ancient microbial genomes from the human gut.” Snow and UM graduate student Tre Blohm are among the 28 authors of the piece, who hail from institutions around the globe.

Snow said the feces they studied came from dry caves in Utah and northern Mexico. So what does the 1,000-year-old human excrement look like?

“The caves these paleofeces came from are known for their amazing preservation,” she said. “Things that would normally degrade over time look almost brand new. So the paleofeces looked like, well, feces that are very dried out.”

Snow and Blohm worked hands-on with the precious specimens, suiting up in a clean-room laboratory at UM to avoid contamination from the environment or any other microorganisms – not an easy task when the tiny creatures are literally in and on everything. They would carefully collect a small portion that allowed them to separate out the DNA from the rest of the material. Blohm then used the sequenced DNA to confirm the paleofeces came from ancient people.

The senior author of the Nature paper is Aleksandar Kostic of the Joslin Diabetes Center. In previous studies of children living in Finland and Russia, he and his partners revealed that kids living in industrialized areas – who are much more likely to develop Type 1 diabetes than those in non-industrialized areas – have very different gut microbiomes.

“We were able to identify specific microbes and microbial products that we believe hampered a proper immune education in early life,” Kostic said. “And this leads later on to higher incidents of not just Type 1 diabetes, but other autoimmune and allergic diseases.”

Kostic wanted to find a healthy human microbiome without the effects of modern industrialization, but he became convinced that couldn’t happen with any modern living people, pointing out that even tribes in the remote Amazon are contracting COVID-19.

So that’s when the researchers turned to samples collected from arid environments in the North American Southwest. The DNA from eight well-preserved ancient gut samples were compared with the DNA of 789 modern samples. Half the modern samples came from people eating diets where most food comes from grocery stores, and the remainder came from people consuming non-industrialized foods mostly grown in their own communities.

The differences between microbiome populations were striking. For instance, a bacterium known as Treponema succinifaciens wasn’t in a single “industrialized” population’s microbiome the team analyzed, but it was in every single one of the eight ancient microbiomes. But researchers found the ancient microbiomes did match up more closely with modern non-industrialized population’s microbiomes.

The scientists found that almost 40% of the ancient microbial species had never been seen before. Kostic speculated on what caused the high genetic variability:

“In ancient cultures, the foods you’re eating are very diverse and can support a more eclectic collection of microbes,” Kostic said. “But as you move toward industrialization and more of a grocery-store diet, you lose a lot of nutrients that help to support a more diverse microbiome.”

Moreover, the ancient microbial populations incorporated fewer genes related to antibiotic resistance. The ancient samples also featured lower numbers of genes that produce proteins that degrade the intestinal mucus layer, which then can produce inflammation that is linked with various diseases.

Snow and several coauthors and museum collection managers also led a project to ensure the inclusion of Indigenous perspectives in the research.

“This was a really vital part of the work that had to accompany this kind of research,” she said. “Initially, we sent out multiple letters and emails and called the tribal historic preservation officers of the all the recognized tribes in the Southwest region. Then we met with anyone who was interested, doing short presentations and answering questions and following up with interested parties.

“The feedback we received was noteworthy, in that we needed to keep in mind that these paleofeces have to ties their ancestors, and we needed to be – and hopefully have been – as respectful as possible about them,” she said.

“There is a long history of misuse of genetic data from Indigenous communities, and we strove to be mindful of this by meeting and speaking with as many people as possible to obtain their insights and perspectives. We hope that this will set a precedent for us as scientists and others working with genetic material from Indigenous communities past and present.”

Snow said the research overall revealed some fascinating things.

“The biggest finding is that the gut microbiome in the past was far more diverse than today – and this loss of diversity is something we are seeing in humans around the world,” she said. “It’s really important that we learn more about these little microorganisms and what they do for us in our symbiotic relationships.

“In the end, it could make us all healthier.”

###

Coinsmart. Beste Bitcoin-Börse in Europa
Source: https://bioengineer.org/research-reveals-ancient-people-had-more-diverse-gut-microorganisms/

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