Study in a Sentence: Researchers demonstrated SARS-CoV-2 infection in human tissue samples of olfactory mucosa (the outer layers of tissue in the nose) and its neuronal projections into the central nervous system (CNS), indicating that the virus can exploit the olfactory system to cross into the CNS.
Healthy for Humans: CNS-related symptoms of COVID-19 are well-defined and include loss of smell and taste, headache, fatigue, nausea, vomiting, cerebrovascular disease, and impaired consciousness, but their pathogenesis is not well understood. To better understand COVID-19 diagnosis, prognosis, and treatments, researchers aimed to characterize how SARS-CoV-2 infects cells of the human olfactory system, a potential entryway for the virus into the CNS.
Redefining Research: In the first systematic analysis of human post-mortem olfactory and brain tissue, samples were collected from 33 individuals with confirmed COVID-19. Signatures of infection in the olfactory mucosa and its neuronal projections into the CNS suggest that SARS-CoV-2 follows olfactory neuroanatomical structures to penetrate the brain and CNS, potentially explaining the neurological symptoms of COVID-19.
Meinhardt J, Radke J, Dittmayer C, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nature Neuroscience. 2020. https://doi.org/10.1038/s41593-020-00758-5.
Researchers tracked adherence to and healthfulness of a plant-based diet in participants from the Health Professionals Follow-up Study and monitored diabetes rates. Those who strayed away from a healthful plant-based diet had a 12% to 23% increased risk for type 2 diabetes when compared to those who consistently followed a healthful plant-based diet.
Results also showed that improved adherence to healthful plant-based diets rich in whole grains, legumes, fruits, and vegetables lowered the risk for diabetes. Increased fiber intake and consumption of polyphenols from plant-based foods and reductions in animal fat consumption improve weight, gut microbiota, inflammation, and other biomarkers associated with type 2 diabetes.
Chen Z, Drouin-Chartier JP, Li Y, et al. Changes in plant-based diet indices and subsequent risk of type 2 diabetes in women and men: Three U.S. prospective cohorts. Diabetes Care. Published January 13, 2021. https://doi.org/10.2337/dc20-1636.
A low-fat, plant-based diet reduced daily calorie intake and body fat more than a low-carbohydrate, animal-based diet high in fat, according to a study published in Nature Medicine.
Researchers with the National Institutes of Health Clinical Center’s Metabolic Clinical Research Unit randomly assigned 20 participants to either a low-fat vegan diet or a low-carbohydrate diet for a two-week period, carefully tracking their calorie intake, body weight, blood sugar, and other biomarkers. Participants then switched to the other diet for an additional two weeks for comparison.
Results showed that participants consumed up to 700 fewer daily calories during the low-fat, plant-based diet, when compared to the low-carbohydrate diet. But there were no differences in satiety, meaning the vegan diet allowed people to eat less food without hunger. While both groups lost weight, only the low-fat diet resulted in significant reductions in body fat.
Consumption of fried foods was associated with a higher risk for heart disease, according to a meta-analysis published online in Heart.
Researchers compared fried food intake and heart disease in 17 studies that encompassed data for more than 500,000 participants. Consumption of the highest amount of fried foods such as fried fish compared to the lowest consumption of fried foods increased the risk for major cardiovascular events, coronary heart disease, and heart failure by 28%, 22%, and 37%, respectively.
Results showed additional weekly servings of fried foods increased the risk by 2% to 3%. High consumption of saturated fat and sodium, increased energy intake, and other dietary habits associated with fried food consumption may account for the elevated risk and associated chronic diseases such as diabetes and obesity.
Qin P, Zhang M, Han M, et al. Fried-food consumption and risk of cardiovascular disease and all-cause mortality: A meta-analysis of observational studies. Heart. Published online January 19, 2021. doi: 10.1136/heartjnl-2020-317883.
Hernias are one of the most common soft tissue injuries. Hernias form when intra-abdominal content, such as a loop of the intestine, squeezes through weak, defective or injured areas of the abdominal wall.
The condition may develop serious complications, therefore hernia repair may be recommended. Repair consists of surgically implanting a prosthetic mesh to support and reinforce the damaged abdominal wall and facilitate the healing process. However, currently used mesh implants are associated with potentially adverse postsurgical complications.
“Although hernia mesh implants are mechanically strong and support abdominal tissue, making the patient feel comfortable initially, it is a common problem that about three days after surgery the implant can drive inflammation that in two to three weeks will affect organs nearby,” said Dr. Crystal Shin, assistant professor of surgery at Baylor College of Medicine and lead author of this study looking to find a solution to postsurgical hernia complications.
Mesh implants mostly fail because they promote the adhesion of the intestine, liver or other visceral organs to the mesh. As the adhesions grow, the mesh shrinks and hardens, potentially leading to chronic pain, bowel obstruction, bleeding and poor quality of life. Some patients may require a second surgery to repair the unsuccessful first. “Inflammation is also a serious concern,” said Dr. Ghanashyam Acharya, associate professor of surgery at Baylor. “Currently, inflammation is controlled with medication or anti-inflammatory drugs, but these drugs also disturb the healing process because they block the migration of immune cells to the injury site.”
“To address these complications, we developed a non-pharmacological approach by designing a novel mesh that, in addition to providing mechanical support to the injury site, also acts as an inflammation modulating system,” Shin said.
“A major innovation to our design is the development of a Biomesh that can reduce inflammation and, as a result, minimize tissue adhesion to the mesh that leads to pain and failure of the surgery,” Shin said.
Inflammatory mediators called cytokines appear where the mesh is implanted a few days after the surgery. Some of the main cytokines in the implant, IL1-β, IL6 and TNF-α, have a positive surface charge due to the presence of the amino acids lysine and arginine.
“We hypothesized that Biomesh with a negative surface charge would capture the positively charged cytokines, as opposite electrical charges are attracted to each other,” Acharya said. “We expected that trapping the cytokines in the mesh would reduce their inflammatory effect and improve hernia repair and the healing process.”
To test their new idea, the researchers used a 3-D-bioprinter to fabricate Biomesh of a polymer called phosphate crosslinked poly (vinyl alcohol) polymer (X-PVA). Through thorough experimentation, they optimized the mechanical properties so the mesh would withstand maximal abdominal pressure repeatedly without any deterioration of its mechanical strength for several months. They also showed that their Biomesh did not degrade or reduce its elastic properties over time and was not toxic to human cells.
Shin, Acharya and their colleagues have confirmed in the lab that this Biomesh can capture positively charged cytokines. Encouraged by these results, the researchers tested their Biomesh in a rat model of hernia repair, comparing it with a type of mesh extensively used clinically for surgical hernia repair.
Newly designed 3-D printed Biomesh minimizes postsurgical complications of hernia repair in an animal model
The newly designed Biomesh effectively minimized postsurgical complications of hernia repair in an animal model. The researchers examined the Biomesh for four weeks after it was implanted. They found that the newly designed Biomesh had captured about three times the amount of cytokines captured by the commonly used mesh. Cytokines are short-lived in the body. As they degrade, they enable the mesh to capture more cytokines.
Importantly, no visceral tissues had adhered to the newly designed Biomesh, while the level of tissue adhesion was extreme in the case of the commonly used mesh. These results confirmed that the new Biomesh is effective at reducing the effects of the inflammatory response and in preventing visceral adhesions. In addition, the new mesh did not hinder abdominal wall healing after surgical hernia repair in animal models.
“This Biomesh is unique and designed to improve outcomes and reduce acute and long-term complications and symptoms associated with hernia repair. With more than 400,000 hernia repair surgeries conducted every year in the U.S., the new Biomesh would fulfill a major unmet need,” Shin said. “There is no such multifunctional composite surgical mesh available, and development of a broadly applicable Biomesh would be a major advancement in the surgical repair of hernia and other soft tissue defects. We are conducting further preclinical studies before our approach can be translated to the clinic. Fabricating the Biomesh is highly reproducible, scalable and modifiable.”
“This concept of controlling inflammation through the physicochemical properties of the materials is new. The mesh was originally designed for mechanical strength. We asked ourselves, can we create a new kind of mesh by making use of the physical and chemical properties of materials?” said Acharya. “In the 1950s, Dr. Francis C. Usher at Baylor’s Department of Surgery developed the first polypropylene mesh for hernia repair. We have developed a next-generation mesh that not only provides mechanical support but also plays a physiological role of reducing the inflammatory response that causes significant clinical problems.” Read the complete study in the journal Advanced Materials.
Other contributors to this work include Fernando J. Cabrera, Richard Lee, John Kim, Remya Ammassam Veettil, Mahira Zaheer, Kirti Mhatre and Bradford G. Scott who are affiliated with Baylor College of Medicine. Aparna Adumbumkulath and Pulickel M. Ajayan are at Rice University and Steven A. Curley is at Christus Health Institute.
This work was supported by Baylor College of Medicine seed funding.
Current research interests of the Shin lab focus on developing broadly applicable drug delivery systems for surgical applications with enhanced therapeutic efficacy by integrating nanotechnology and 3-D bioprinting technology. She is currently working on developing controlled release nanowafer therapeutics (a hydrogel-based drug delivery system), nanodrug delivery systems for wound healing and pain management, and theranostics, a combination of therapeutics and diagnostics, for image-guided drug delivery.
Acharya’s research program focuses on the development of advanced materials for regenerative engineering by integrating nanofabrication, 3-D-nanolithography and controlled drug delivery strategies. He works at the interface of medicine, bioengineering, chemistry and pharmaceutics.
Despite being one of the most common spinal surgeries, anterior cervical discectomy and fusion, a type of treatment for forms of degenerative disc disease, is a major procedure that sometimes fails in certain high-risk patients and situations. Doctors with Baylor College of Medicine and Baylor Medicine’s Spine Center, as well as Baylor St. Luke’s Medical Center are now part of the FUSE study, a multicenter clinical trial working to find a tissue-sparing approach to increase the success rate of neck fusion surgery to treat nerve compression and neck pain.
Degenerative disc disease is a condition that causes pain because the discs that usually provide cushion in the spine have worn away due to age or injury. The pain can radiate down the neck, shoulder and arms. Sometimes, bone spurs or a disc herniation can result, causing nerve or spinal cord compression that can be disabling. The common treatment is to remove the disc and bone spurs from the front of the neck and then have the two adjacent vertebrae fuse together – an anterior cervical discectomy and fusion (ACDF).
“An ACDF decompresses the spine, then permanently fuses the bones together to reduce continued degeneration,” said Dr. David Xu, assistant professor of neurosurgery at Baylor and surgeon with Baylor St. Luke’s Medical Center. “The surgery requires a small incision through the front of the neck and is successful more than 95% of the time when treating a single level of the vertebra.”
However, when treating high-risk patients such as those with diabetes, kidney disease or osteoporosis, or when needing to fuse multiple levels, failure is more common. According to Xu, “fusion failure can sometimes exceed 20 percent when three or more discs need treatment.”
Traditionally, the way to prevent or treat fusion failure is to supplement the ACDF by making a big incision in the back of the neck and installing screws and rods, resulting in the disruption of muscles and soft tissues. In the current study, a unique set of implants are used to achieve the same supplemental stabilization without the big incision. The devices are inserted into the back of the neck through two small one-centimeter incisions using a unique set of instruments called the CORUS Spinal System. The process is tissue-sparing and drastically reduces muscle disruption and blood loss.
The Fuse Trial is a prospective, randomized, controlled study, which means participants will be randomly chosen to receive ACDF alone or ACDF plus supplemental stabilization with posterior cervical stabilization system (PCSS). The trial will determine if ACDF plus PCSS will result in superior clinical outcomes versus ACDF alone in the treatment of 3-level cervical degenerative disease.
“The goal of this study is to find the most effective method for positive outcomes in high-risk patients, specifically for ACDFs spanning three levels,” Xu said. “We want to help create the gold standard for this type of surgery, making it easier for patients to recover with minimal damage to the muscles in the neck.”
The study is seeking to enroll 330 patients. Participants should be between 18 to 80 years of age and have been recommended for ACDF treatment for degenerative disc disease between and including the C3-C7 vertebrae. The study is sponsored by Providence Medical Technology.
The imaging time window of 64Cu-DOTATATE positron emission tomography/computed tomography (PET/CT) for patients with neuroendocrine neoplasms can be expanded from one hour to three hours post-injection, according to new research published in the January issue of The Journal of Nuclear Medicine. In a head-to-head comparison of scans performed at the two time intervals, there were no significant differences in the number of lesions detected, and tumor-to-normal tissue ratios remained high in all key organs.
Previous research has demonstrated that 64Cu-DOTATATE PET imaging at one hour post-injection provides excellent lesion detection in patients with neuroendocrine neoplasms. “Given the long half-life and excellent image resolution of 64Cu-DOTATATE, we sought to investigate if the imaging time window for 64Cu-DOTATATE PET could be expanded from one hour to up to three hours without a loss in the ability to detect lesions,” said Andreas Kjaer, MD, PhD, DMSc, professor at University of Copenhagen and chief physician at Rigshospitalet, the National University Hospital of Denmark, both in Copenhagen, Denmark.
In the prospective study, 35 patients with neuroendocrine neoplasms received 64Cu-DOTATATE whole-body PET imaging at both one hour post-injection and three hours post-injection. The number of lesions on the scans were counted and grouped according to organs or regions and were then compared. Uptake of 64Cu-DOTATATE in lesions and normal tissues was measured, and tumor-to-normal tissue ratios were calculated.
A total of 882 concordant lesions (visible on both the one-hour and three-hour post-injection 64Cu-DOTATATE PET) were found. Five discordant lesions, which were found on one of the PET scans but not the other, were noted; however, only four were considered true based on further imaging. Throughout the one to three hour post-injection imaging window, the tumor-to-normal tissue ratios were high in all key organs, including the liver, intestines, pancreas and bone.
“The high agreement in the number of lesions detected on both the one-hour and three-hour post-injection 64Cu-DOTATATE PET supports the rationale of expanding the imaging time window,” stated Kjaer. “Since 64Cu-DOTATATE has a shelf-life of 24 hours, which is much longer than other PET imaging options, it offers greater convenience and flexibility for routine imaging of patients with neuroendocrine neoplasms. We expect to see more 64Cu-labeled PET tracers for routine use in the future.”
Neuroendocrine neoplasms represent a heterogeneous class of diseases with large variability in aggressiveness and prognosis. These rare tumors most frequently originate from the pancreas, the gastrointestinal tract or the lung. Approximately 12,000 Americans are diagnosed with neuroendocrine neoplasms each year.
The authors of “64Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Prospective, Head-to-Head Comparison of Imaging at 1 Hour and 3 Hours Post-Injection,” include Mathias Loft, Esben A. Carlsen, Camilla B. Johnbeck, Helle H. Johannesen, Tina Binderup, Andreas Pfeifer, Jann Mortensen, Peter Oturai, Annika Loft, Anne K. Berthelsen and Andreas Kjaer, Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark; Seppo W. Langer, Department of Oncology, Rigshospitalet, Copenhagen, Denmark, and Ulrich Knigge, Departments of Clinical Endocrinology and Surgical Gastroenterology, Rigshospitalet, Copenhagen, Denmark. All departments are part of ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.
Reference: Mathias Loft, Esben A. Carlsen, Camilla B. Johnbeck, Helle H. Johannesen, Tina Binderup, Andreas Pfeifer, Jann Mortensen, Peter Oturai, Annika Loft, Anne K. Berthelsen, Seppo W. Langer, Ulrich Knigge and Andreas Kjaer, “64Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Prospective, Head-to-Head Comparison of Imaging at 1 Hour and 3 Hours After Injection”, Journal of Nuclear Medicine January 2021, 62 (1) 73-80; DOI: https://doi.org/10.2967/jnumed.120.244509https://jnm.snmjournals.org/content/62/1/73
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An international team of astronomers led by researchers from the Netherlands has discovered a whirlwind of dust and pebbles in orbit around a young star. It is possible that a planet is forming in the pebbles. The team of scientists made the discovery during the time that designers and developers of an astronomical instrument get as a reward for their work. They will soon publish their findings in the journal Astronomy & Astrophysics.
The exoplanet-in-the-making orbits the star HD 163296 in a close orbit. HD 163296 is a young star much studied by astronomers about 330 light-years away from Earth in the constellation of Sagittarius. Previously, astronomers found evidence for the formation of three large exoplanets in a wide orbit around the star. Now, they may be adding a fourth planet close to the star.
The researchers led by Jozsef Varga (Leiden University, the Netherlands) studied the star during four nights in March and June 2019. They had focused their telescope on the inner part of the disk of dust and pebbles that orbit the star. The astronomers observed a ring of warm, fine dust at a distance from the star comparable to Mercury’s orbit around our Sun. What was striking was that one part of the ring was much brighter, i.e. hotter, than the rest of the ring. This hot spot seemed to orbit the star in one month.
The astronomers suspect that the hot spot of warm, fine dust is a vortex in the disk from which a planet could be formed. They can support their suspicion with simulations. While in the rest of the disk dust and pebbles clump together, in the vortex the pebbles are actually ground into fine dust. That fine dust is visible in the hot spot.
The researchers made their discovery with the new MATISSE instrument. That instrument combines and analyzes light from four telescopes of the ESO Observatory’s Very Large Telescope on Cerro Paranal, in northern Chile. This creates a combined telescope with a virtual diameter of 200 meters. The MATISSE instrument is made especially to analyze infrared radiation. Such radiation is created when an object, such as a planet or dust disk gives off heat. The instrument is cooled to prevent it from emitting infrared radiation itself.
The Netherlands Research School for Astronomy (NOVA) built all the lenses and mirrors in the cooled part of MATISSE together with Dutch industry. In 2018, MATISSE saw its “first light” with a series of test observations.
For the researchers and engineers from, amongst others, Leiden University, University of Amsterdam, Radboud University Nijmegen, SRON and the NOVA Optical Infrared Group, this first, real scientific result marks the beginning of further research. One of the goals is to study more stars with dust disks and especially dust disks in which earthlike planets can form.
Reference: J. Varga, M. Hogerheijde, R. van Boekel, L. Klarmann, R. Petrov, L.B.F.M. Waters, S. Lagarde, E. Pantin, Ph. Berio, G. Weigelt, S. Robbe-Dubois, B. Lopez, F. Millour, J.-C. Augereau, H. Meheut, A. Meilland, Th. Henning, W. Jaffe, F. Bettonvil, et al., “The asymmetric inner disk of the Herbig Ae star HD 163296 in the eyes of VLTI/MATISSE: evidence for a vortex?”, Astronomy & Astrophysics, 2021. (Original paper, free preprint)
Researchers from the Institute of Astrophysics of Andalusia (IAA-CSIC) are leading an ambitious radio observation project that shows that extrasolar planets can be detected with radio telescopes.
For two decades it has been known that the magnetic interaction between Jupiter and one of its largest moons, Io, generates a large amount of radio emission similar to terrestrial auroras (produced, in turn, by the interaction of electrically charged particles from the Sun with the Earth’s atmosphere). After the discovery of the planet Proxima b around the star closest to us, Proxima Centauri, a group of researchers from the IAA-CSIC set out to check whether radio interactions also occur in this neighboring solar system. Their finding opens a new path in the study of extrasolar planets.
“This type of radio emission is possible because the Proxima planetary system has particular properties: it is a much more active star than our Sun and the planet Proxima b is very close to it; in fact, it is ten times closer to its star than Mercury is to the Sun”, points out Miguel Pérez-Torres, researcher at the Institute of Astrophysics of Andalusia (IAA-CSIC) who is leading the study.
The observation campaign was carried out with the ATCA (Australia Telescope Compact Array), a radio telescope made up of six twenty-two-meter antennas, and lasted for seventeen terrestrial days. As planet Proxima b makes a complete revolution around its star every 11.2 days (much less than the 365 days of Earth’s orbit), the researchers observed the emission from the Proxima planetary system for the equivalent of a year and a half.
“We detected radio emission during most of the observation campaign, with times of more intense emission. These peaks were detected twice for each orbital period, when the planet is, seen from Earth, more separated from its star -says José Francisco Gómez, IAA-CSIC researcher who participates in the study-. The data we have obtained agrees very well with what models of interaction between the star and the planet predict”.
This is a pioneering work, since it shows for the first time that the existence of a planet outside the Solar System can be detected by observing the periodic variations of the system with radio telescopes. “This opens a new path for the study of other planets that, in some cases, could not be detected by other techniques, and that is very promising when we think about the exceptionally sensitive radio telescopes that are in development, such as the Square Kilometer Array (SKA)”, indicates Miguel Pérez-Torres (IAA-CSIC).
This work has also made it possible to detect several radio flashes lasting just a few minutes, which respond to brief episodes of activity in the star, as well as a stellar flare that lasted for three days and whose radio brightness was ten times higher than the usual of the star. “These results are also interesting in regards to the possibility of Proxima b harboring life. These radio wave flares must have been very strong for us to detect them, and some have lasted for days. Forms of life like those on Earth could not possibly survive this type of event”, points out José Francisco Gómez (IAA-CSIC).
In this study have participated, in addition to researchers from the IAA-CSIC, also researchers from the Institut de Ciències del Espai (ICE-CSIC) in Barcelona, the Osservatorio de Catania (INAF, Italy), the Universidad de Chile, and from the North-West University in South Africa.
FOUR YEARS OBSERVING PROXIMA FROM THE IAA-CSIC
In 2016, the international observation campaign RedDots, in which the IAA-CSIC participated, focused four telescopes on the star closest to us after the Sun, Proxima Centauri. They sought to detect the slight gravitational pull that a possible planet would exert on the star, which forces it to draw a small orbit and is translated into oscillations in its light. This is how Proxima b was found, a planet with a minimum mass equivalent to 1.3 times that of the Earth and that revolves around Proxima Centauri every 11.2 days within the habitable zone, or the region around a star with favorable conditions for the existence of liquid water on the surface.
In 2017, researchers from the Institute of Astrophysics of Andalusia (IAA-CSIC) discovered a dust belt around Proxima through observations with the ALMA interferometer. Similar to the Kuiper Belt of our Solar System, it represented the discovery of remnant material from the formation of the planetary system closest to ours.
In January 2020, the discovery, also with the participation of the IAA-CSIC, of a possible second planet around Proxima Centauri was announced, thanks to data collected from Chile with the UVES and HARPS spectrographs of the European Southern Observatory (ESO). The observations, which spanned a total of seventeen years, revealed the presence of a signal with a period of 5.2 years compatible with the existence of a second planet around Proxima Centauri with a minimum mass of about six times that of Earth.
“A project of this kind could only be carried out because IAA specialists in various fields (physics of the atmospheres of the planets of the Solar System, stellar physics, search and study of exoplanets and processes of the interstellar medium) have joined forces and knowledge. This includes their experience both in theoretical modeling and in multi-wavelength observations, from radio to optical and infrared”, concludes Antxon Alberdi, director of the IAA-CSIC and participant in the study.
Video: Model of the auroral emission arising from the interaction between the planet Proxima b (the small circle in the movie) and its host star Proxima Centauri (the big circle). During its revolution around Proxima Centauri, the planet Proxima b impacts the host star magnetosphere (the green lines in the movie), accelerating charged electrons that propagate towards the magnetic poles of the star (orange lines). This process leads to abundant radio emission, which can be seen from Earth only when the star occupies particular phases of its rotation. The radio emission is also polarized, so that when the emission comes from the Northern hemisphere of the star magnetosphere, the light is polarized clockwise (RCP in the movie) and, when the emission comes from the Southern hemisphere, the light is polarized anti-clockwise (LCP in the movie). Credits: Corrado Trigilio (INAF, Italy).