Brain

Study finds botanical effective for chemo-resistant colon cancer

DUARTE, Calif. -- The natural botanical Andrographis paniculata, when given in conjunction with chemotherapy, may eventually change the way doctors treat chemotherapy-resistant colorectal cancer, reports a new City of Hope study.

Published in the journal Carcinogenesis, the study's goal was to use a natural substance that, given as an adjunct treatment along with chemotherapy, would not only be nontoxic but would succeed in killing chemo-resistant cancer cells.

Currently, in an attempt to provide some help for these chemo-resistant patients, other types of chemotherapies are given -- but cancer usually finds a way to outsmart them. What's more, these drugs are highly toxic and can do further harm to the patient.

A Three-Part Study

Andrographis is commonly used in South Asia and is also available in the U.S. It's known for its anti-inflammatory, antibacterial and antiviral properties, and increasingly, for its ability to fight cancer.

"Many, many scientific articles have been published showing that andrographis kills cancer cells. That's not the news," said Ajay Goel, Ph.D., M.S., founding chair of City of Hope's Department of Molecular Diagnostics and Experimental Therapeutics and corresponding author of the study. "The problem is, how do we kill these 'super cells' that have become chemo-resistant?"

To tackle this challenge, his study tested the efficacy of using a standard chemotherapy for colon cancer, 5-fluorouracil (5FU), alone and combined with andrographis. The study proceeded in three parts.

First, they used cell lines of human colorectal cancer, cultivated in the lab. The combination treatment proved far more effective in killing cancer cells than the chemotherapy alone.

Cell lines do not represent the whole body, so the next step was to look at the effects of using animal tissue. Here too, combining andrographis with 5FU was a more potent cancer killer than 5FU alone.

Knowing that it worked on an animal model, the next step was to further confirm these findings in a 3D-organoid model, grown from human colorectal tumor tissue excised from an actual patient. Again, the combination far outperformed chemotherapy alone in killing cancer cells.

How Andrographis Kills Cancer

"In cancer there are hundreds of pathways that are malfunctioning, and modern therapies are designed to target a specific gene or molecule or pathway," Goel said. "It can give patients relief in the short term, but sometimes the cancer says, 'No problem. We have 100 different ways to survive.' Unlike many of the targeted therapies we use in cancer patients, natural treatments are unique, as they don't target a specific pathway but work on many pathways."

What this study showed is that two major pathways were altered by the andrographis.

One is the ferroptosis pathway, which regulates programmed cell death. Under normal conditions it signals old cells that it's time to die, and they are replaced by new ones. But in cancer, the ferroptosis pathway becomes defective. Old cells don't die; new ones keep coming and a tumor forms.

The other is the β-catenin/Wnt-signaling pathway, which involves cell metabolism, a process that goes haywire in cancer. Cancer cells become hyperactive and channel nutrition away from normal cells.

"After exposure to andrographis, the ferroptosis signals were turned back on, which told the cells, 'Yep, it's time to die,'" Goel said. "And the metabolic process was regulated, taking nutrition away from the cancer cells, allowing them to die."

The next step will be to test 5FU and andrographis in a clinical setting, and Goel will soon submit an application for Food and Drug Administration approval.

This combination of natural botanical and potent pharmaceutical promises to bring new hope to patients who have developed chemo-resistance or suffer a relapse of their colon cancer.

Nature's Own Medicine

In addition to the andrographis study, Goel has done several others, including an earlier study in Carcinogenesis and another in the journal of the American Association for Cancer Research. This work revealed that two herbs, curcumin (found in turmeric) and boswellic acid, were able to regulate certain microRNAs found in human colorectal cancer, suggesting that these substances would be useful for disease prevention.

In fact, because these substances can be protective, he feels that people should start taking them before cancer has a chance to develop.

Credit: 
City of Hope

A chemist from RUDN developed a new type of one-molecule thick water-repellent film

image: A chemist from RUDN University together with colleagues created a new type of two-dimensional nanofilm from an organic material called calixarene. The invention can be used as a protective coating in electronics and as a part of molecular filters. They also suggested a way of increasing the durability of such films with UV radiation.

Image: 
RUDN University

A chemist from RUDN University together with colleagues created a new type of two-dimensional nanofilm from an organic material called calixarene. The invention can be used as a protective coating in electronics and as a part of molecular filters. They also suggested a way of increasing the durability of such films with UV radiation. The results of the study were published in the Materials Today Communications journal.

Calixarenes are large bowl-shaped organic molecules that consist of several rings. The outer ring of the bowl is hydrophilic, i.e. actively retains water. The innermost ring is hydrophobic or water-repellent. Calixarenes are known in the chemical industry as additives: for example, they play a role in the synthesis of ethylene and propylene polymers. Scientists from Belarus and Russia, including a chemist from RUDN University suggested a new way of using them. They developed 0.8-1.5 nm thick calixarene-based films that can work as water-repellent coatings.

"These 2D organic films can be used to create protective hydrophobic or anti-corrosion coatings for organic electronics or to develop molecular filters," said Alexey Kletskov, a Candidate of Chemical Sciences, and a researcher at the Joint Institute for Chemical Research, RUDN University.

The team used the Langmuir-Blodgett method to construct a thin film from single molecules. The method had been developed especially for the molecules that have both hydrophilic and hydrophobic parts. When put in water, molecules like this align on the surface with their hydrophobic parts turned up. After that, they are pressed with special plungers, and when the required density is reached, the film is moved onto a solid base.

To strengthen the film, the team used UV radiation. It has enough energy to break down hydrocarbon chains that bind the outer and inner rings of each molecule together. First the chains are broken, and then they bind again, but this time with loose ends from other calixarene molecules. As a result, all molecules in the film become closely tied together.

The team studied the structure of the films using an atomic-force microscope and found out that the efficiency of UV radiation correlates with the length of the chains in the original macromolecules. Molecules with short chains formed more stable films, and in the case of long-chain molecules, UV radiation caused the films to have irregular structure with clusters. Therefore, UV light was found to not always be beneficial for film quality. Depending on the molecule structure, it can reduce the water-repellent properties of a film or have no considerable effect at all. It is an important factor to consider when using the films as hydrophobic coatings on different surfaces, from displays to construction coatings.

Credit: 
RUDN University

Seeing objects through clouds and fog

image: A three-dimensional reconstruction of the reflective letter "S," as seen through the 1-inch-thick foam.

Image: 
Stanford Computational Imaging Lab

Like a comic book come to life, researchers at Stanford University have developed a kind of X-ray vision - only without the X-rays. Working with hardware similar to what enables autonomous cars to "see" the world around them, the researchers enhanced their system with a highly efficient algorithm that can reconstruct three-dimensional hidden scenes based on the movement of individual particles of light, or photons. In tests, detailed in a paper published Sept. 9 in Nature Communications, their system successfully reconstructed shapes obscured by 1-inch-thick foam. To the human eye, it's like seeing through walls.

"A lot of imaging techniques make images look a little bit better, a little bit less noisy, but this is really something where we make the invisible visible," said Gordon Wetzstein, assistant professor of electrical engineering at Stanford and senior author of the paper. "This is really pushing the frontier of what may be possible with any kind of sensing system. It's like superhuman vision."

This technique complements other vision systems that can see through barriers on the microscopic scale - for applications in medicine - because it's more focused on large-scale situations, such as navigating self-driving cars in fog or heavy rain and satellite imaging of the surface of Earth and other planets through hazy atmosphere.

Supersight from scattered light

In order to see through environments that scatter light every-which-way, the system pairs a laser with a super-sensitive photon detector that records every bit of laser light that hits it. As the laser scans an obstruction like a wall of foam, an occasional photon will manage to pass through the foam, hit the objects hidden behind it and pass back through the foam to reach the detector. The algorithm-supported software then uses those few photons - and information about where and when they hit the detector - to reconstruct the hidden objects in 3D.

This is not the first system with the ability to reveal hidden objects through scattering environments, but it circumvents limitations associated with other techniques. For example, some require knowledge about how far away the object of interest is. It is also common that these systems only use information from ballistic photons, which are photons that travel to and from the hidden object through the scattering field but without actually scattering along the way.

"We were interested in being able to image through scattering media without these assumptions and to collect all the photons that have been scattered to reconstruct the image," said David Lindell, a graduate student in electrical engineering and lead author of the paper. "This makes our system especially useful for large-scale applications, where there would be very few ballistic photons."

In order to make their algorithm amenable to the complexities of scattering, the researchers had to closely co-design their hardware and software, although the hardware components they used are only slightly more advanced than what is currently found in autonomous cars. Depending on the brightness of the hidden objects, scanning in their tests took anywhere from one minute to one hour, but the algorithm reconstructed the obscured scene in real-time and could be run on a laptop.

"You couldn't see through the foam with your own eyes, and even just looking at the photon measurements from the detector, you really don't see anything," said Lindell. "But, with just a handful of photons, the reconstruction algorithm can expose these objects - and you can see not only what they look like, but where they are in 3D space."

Space and fog

Someday, a descendant of this system could be sent through space to other planets and moons to help see through icy clouds to deeper layers and surfaces. In the nearer term, the researchers would like to experiment with different scattering environments to simulate other circumstances where this technology could be useful.

"We're excited to push this further with other types of scattering geometries," said Lindell. "So, not just objects hidden behind a thick slab of material but objects that are embedded in densely scattering material, which would be like seeing an object that's surrounded by fog."

Lindell and Wetzstein are also enthusiastic about how this work represents a deeply interdisciplinary intersection of science and engineering.

"These sensing systems are devices with lasers, detectors and advanced algorithms, which puts them in an interdisciplinary research area between hardware and physics and applied math," said Wetzstein. "All of those are critical, core fields in this work and that's what's the most exciting for me."

Credit: 
Stanford University

ENT physicians and researchers showcase studies at Otolaryngology's Virtual Annual Meeting

ALEXANDRIA, VA-- During the AAO-HNSF 2020 Virtual Annual Meeting & OTO Experience, which runs from September 13 through October 25, the most current research in otolaryngology-head and neck surgery will be introduced during the Scientific Oral Presentations. Scientific Oral Presentations are a series of three- to six-minute presentations focusing on current evidence-based research, surgical procedures, and approaches in clinical sciences and their application to patient care.

The 2020 Virtual Annual Meeting includes hundreds of research presentations. The Program Committee, comprised of physician members, selected 14 studies to highlight in recognition of outstanding scientific merit and innovation. These studies have earned the recognition of "Best of Orals." The following selected studies earned this designation and are included in the library of Scientific Oral Presentations, which are available to all attendees at their convenience via on-demand in the Virtual Annual Meeting platform:

A Quantitative Comparison of Smartphone-Based Endoscopy and Traditional Tower Endoscopy
Matthew Maksimoski, MD (Presenter); Sarah Maurrasse, MD; Taher Valika, MD

Adaptable Essential Oil Olfactory Test: Comparison of Affordable Rapid Olfaction Measurement Array to Sniffin' Sticks
Jennifer Li, MD (Presenter); Gracie Palmer; Kevin J. Sykes, PhD, MPH; Mark Villwock, MS; Alexander G. Chiu, MD; Jennifer A. Villwock, MD

Adverse Events in Hypoglossal Nerve Stimulation: Analysis of the FDA Manufacturer and User Facility Device Experience
Nikhil Bellamkonda (Presenter); Abie Mendelsohn, MD; Travis L. Shiba, MD

Clinical Validation of an Automated Deep-Learning-Based Algorithm for Quantitative Sinus Computed Tomography Analysis
Conner J. Massey, MD (Presenter); Daniel Beswick, MD; Vijay R. Ramakrishnan, MD; Stephen Humphries, PhD

Complications With the Hypoglossal Nerve Stimulator: An Analysis of Nationally Reported Adverse Events
Elisa Berson (Presenter); Harold G. Moore; Rema Shah; Yan H. Lee, MD

Effect of Ciprofloxacin + Dexamethasone on Subglottic Fibroblast Proliferation and Function
Nicklas Cary Orobello, MD (Presenter); Beverly R. Wuertz; Luke A. Jakubowski, MD; Motassem Nashawaty; Frank G. Ondrey, MD, PhD

Longitudinal Follow-up for Patients With Chronic Neurogenic Cough Treated With Superior Laryngeal Nerve Block
Vaninder Dhillon, MD (Presenter)

Oral Dexamethasone Following Pediatric Adenotonsillectomy: A Randomized Controlled Trial
Ariana Ghom Greenwell (Presenter); Amal Isaiah, MD, PhD; Judy Oakley, MSN, MPH; Kevin D. Pereira, MD, MS(ORL)

Peritonsillar Abscess Size as a Predictor of Medical Therapy Success
Matthew Urban, MD (Presenter); Cameron Heyd; Thomas Nielsen, MD

Predictors of Otolaryngology Physician Well-being and Burnout
David P. Larson, MD (Presenter); Matthew L. Carlson, MD; Erin K. O'Brien, MD; Christine Lohse, MS; Garret W. Choby, MD

Quality Improvement Initiative to Improve Communication for Acutely Aphonic Patients
Catherine T. Haring, MD (Presenter); Kaitlin Vance; Marie Anna Leginza; Janice Farlow, MD; Robert J. Morrison, MD; Keith A. Casper, MD

Radiographic and Histological Characteristics of Decellularized Trachea in a Mouse Model of Tracheal Replacement
Lumei Liu (Presenter); Sayali Dharmadhikari, MS

Trends in Medicare Reimbursement for Otolaryngology Procedures: 2000-2020
Dominik Greda, MD (Presenter); Feras Ackall, MD; Milap Raikundalia, MD; David Kaylie, MD

Transoral Laser Microsurgery for pTispT2 Glottic Cancer: Long-term Survival Outcomes in 1188 Patients
Alberto Paderno (Presenter); Francesca Del Bon; Giorgio Peretti, MD; Piero Nicolai, MD; Alberto Deganello; Cesare Piazza, MD

Credit: 
American Academy of Otolaryngology - Head and Neck Surgery

The marshmallow test revisited

When kids "pass" the marshmallow test, are they simply better at self-control or is something else going on? A new UC San Diego study revisits the classic psychology experiment and reports that part of what may be at work is that children care more deeply than previously known what authority figures think of them.

In the marshmallow test, young children are given one marshmallow and told they can eat it right away or, if they wait a while, while nobody is watching, they can have two marshmallows instead. The half-century-old test is quite well-known. It's entered everyday speech, and you may have chuckled at an online video or two in which children struggle adorably on hidden camera with the temptation of an immediate treat.

But the real reason the test is famous (and infamous) is because researchers have shown that the ability to wait - to delay gratification in order to get a bigger reward later - is associated with a range of positive life outcomes far down the line, including better stress tolerance and higher SAT scores more than a decade later. Whether or not it's just this ability to wait or a host of other socioeconomic and personality factors that are predictive is still up for debate, but the new study, published in the journal Psychological Science, shows that young children will wait nearly twice as long for a reward if they are told their teacher will find out how long they waited.

This is the first demonstration that what researchers call "reputation management" might be a factor.

"The classic marshmallow test has shaped the way researchers think about the development of self-control, which is an important skill," said Gail Heyman, a University of California San Diego professor of psychology and lead author on the study. "Our new research suggests that in addition to measuring self-control, the task may also be measuring another important skill: awareness of what other people value."

In fact, she said, "one reason for the predictive power of delay-of-gratification tasks may be that the children who wait longer care more about what people around them value, or are better at figuring it out."

For their study, Heyman and her colleagues from UC San Diego and Zhejiang Sci-Tech University conducted two experiments with a total of 273 preschool children in China aged 3 to 4 years old.

The researchers told the children that they could earn a small reward immediately or wait for a bigger one. (Instead of a marshmallow, the researchers used a sticker reward in one of the experiments and a cookie in the other.) Children were assigned to either a "teacher condition" in which they were told that their teacher would find out how long they waited, a "peer condition" in which they were told that a classmate would find out how long they waited, or a "standard condition" that had no special instructions.

Children waited longer in both the teacher and peer conditions than in the standard condition. The difference was about twice as great in the teacher condition as compared to the peer condition. The researchers interpret these results to mean that when children decide how long to wait, they make a cost-benefit analysis that takes into account the possibility of getting a social reward in the form of a boost to their reputation. These findings suggest that the desire to impress others is strong and can motivate human behavior starting at a very young age.

The researchers were surprised by their findings because the traditional view is that 3- and 4-year-olds are too young to care what care what other people think of them.

"The children waited longer in the teacher and peer conditions even though no one directly told them that it's good to wait longer," said Heyman. "We believe that children are good at making these kinds of inferences because they are constantly on the lookout for cues about what people around them value. This may take the form of carefully listening to the evaluative comments that parents and teachers make, or noticing what kinds of people and topics are getting attention in the media."

Credit: 
University of California - San Diego

Vibration device makes homes 'smart' by tracking appliances

ITHACA, N.Y. - To boost efficiency in typical households - where people forget to take wet clothes out of washing machines, retrieve hot food from microwaves and turn off dripping faucets - Cornell University researchers have developed a single device that can track 17 types of appliances using vibrations.

The device, called VibroSense, uses lasers to capture subtle vibrations in walls, ceilings and floors, as well as a deep learning network that models the vibrometer's data to create different signatures for each appliance - bringing researchers closer to a more efficient and integrated smart home.

"Recognizing home activities can help computers better understand human behaviors and needs, with the hope of developing a better human-machine interface," said Cheng Zhang, assistant professor of information science and senior author of "VibroSense: Recognizing Home Activities by Deep Learning Subtle Vibrations on an Interior Surface of a House from a Single Point Using Laser Doppler Vibrometry." The paper was published in Proceedings of the Association for Computing Machinery on Interactive, Mobile, Wearable and Ubiquitous Technologies and will be presented at the ACM International Joint Conference on Pervasive and Ubiquitous Computing, which will be held virtually Sept. 12-17.

"In order to have a smart home at this point, you'd need each device to be smart, which is not realistic; or you'd need to install separate sensors on each device or in each area," said Zhang, who directs Cornell's SciFi Lab. "Our system is the first that can monitor devices across different floors, in different rooms, using one single device."

In order to detect usage across an entire house, the researchers' task was twofold: detect tiny vibrations using a laser Doppler vibrometer; and differentiate similar vibrations created by multiple devices by identifying the paths traveled by the vibrations from room to room.

The deep learning network was trained to distinguish different activities, partly by learning path signatures - the distinctive path vibrations followed through the house - as well as their distinct noises.

The device showed nearly 96% accuracy in identifying 17 different activities across five houses - including dripping faucets, an exhaust fan, an electric kettle, a refrigerator and a range hood - in five houses over two days, according to the paper. VibroSense could also distinguish five different stages of appliance usage with an average accuracy more than 97%.

In single-story houses, the laser was pointed at an interior wall at the center of the home. It was pointed at the ceiling in two-story homes.

The device is primarily useful in single-family houses, Zhang said, because in buildings it could pick up activities in neighboring apartments, presenting a potential privacy risk.

"It would definitely require collaboration between researches, industry practitioners and government to make sure this was used for the right purposes," Zhang said.

Among other uses, the system could help homes monitor energy usage and potentially help reduce consumption.

"Since our system can detect both the occurrence of an indoor event, as well as the time of an event, it could be used to estimate electricity and water-usage rates, and provide energy-saving advice for homeowners," Zhang said. "It could also prevent water and electrical waste, as well as electrical failures such as short circuits in home appliances."

Credit: 
Cornell University

Skin lightening products linked to altered steroid hormone levels

Women who misuse corticosteroid creams for cosmetic skin lightening may be at risk of developing adrenal insufficiency, according to research presented at e-ECE 2020. Women that frequently used high strength steroid creams had significantly lower baseline cortisol levels, a sign of impaired cortisol function. Low cortisol and adrenal insufficiency is a serious condition that causes extreme fatigue and can even lead to death. These findings suggest that better education on the side effects of steroid creams is needed to prevent these women from seriously damaging their health.

The misuse of topical corticosteroids to cosmetically lighten the skin is common among some populations, including Egyptian women. The practice is associated with significant adverse effects such as acne, skin thinning and other skin damage. Yet the practice continues and there is a lack of awareness of these side effects and other potential health risks from prolonged usage. It has been suggested that prolonged usage, particularly at higher doses, could also affect the body's own regulation of the hormone cortisol. Cortisol is released from the adrenal glands and has an important role in the regulation of stress, metabolism and immune function. It is unknown to what extent these topical corticosteroids could be dysregulating normal cortisol function. Low levels of cortisol leads to a condition known as adrenal insufficiency, which is characterised by extreme fatigue, muscle weakness, depression, and if left untreated can cause coma or even death.

In this study, Dr Hany Khairy Mansour and colleagues at Ain Shams University in Cairo, measured the baseline cortisol levels (at 8am), BMI and blood pressure of 45 women who had been using topical corticosteroid creams for at least three months, and compared with women who had not used these creams. The team found that cortisol levels were lower in women using more potent corticosteroid creams, as well as in frequent users who applied it to larger areas of the body. Those using lower strength creams (e.g. 1% hydrocortisone) did not have significantly different cortisol levels. Additionally, there were no significant differences reported for BMI or blood pressure.

Dr Hany Khairy Mansour says, "The use of topical corticosteroids to lighten the skin is common in Egypt, particularly among younger women with lower socioeconomic status, but few are aware of the side effects and potentially serious health problems they can cause."

Dr Mansour advises, "We need to raise awareness of the serious complications associated with the misuse of topical corticosteroids to young Egyptian women. Over-the-counter sale of these high strength steroid creams should be restricted and prescription only. I would like to see government policymakers devising measures for appropriate health education on the health hazards associated with persistent cosmetic use of topical steroids."

Although these results point towards a risk of adrenal insufficiency in persistent users of high strength steroid creams for cosmetic purposes, this was a small study and more investigation is required to confirm these findings. Dr Mansour hopes to extend these findings by looking at cortisol levels in urine, over a 24 hour period, which is a much more sensitive measure of abnormal adrenal gland activity and possible adrenal insufficiency.

Credit: 
European Society of Endocrinology

Study pinpoints process that might have led to first organic molecules

New research led by the American Museum of Natural History and funded by NASA identifies a process that might have been key in producing the first organic molecules on Earth about 4 billion years ago, before the origin of life. The process, which is similar to what might have occurred in some ancient underwater hydrothermal vents, may also have relevance to the search for life elsewhere in the universe. Details of the study are published this week in the journal Proceedings of the National Academy of Sciences.

All life on Earth is built of organic molecules--compounds made of carbon atoms bound to atoms of other elements such as hydrogen, nitrogen and oxygen. In modern life, most of these organic molecules originate from the reduction of carbon dioxide (CO2) through several "carbon-fixation" pathways (such as photosynthesis in plants). But most of these pathways either require energy from the cell in order to work, or were thought to have evolved relatively late. So how did the first organic molecules arise, before the origin of life?

To tackle this question, Museum Gerstner Scholar Victor Sojo and Reuben Hudson from the College of the Atlantic in Maine devised a novel setup based on microfluidic reactors, tiny self-contained laboratories that allow scientists to study the behavior of fluids--and in this case, gases as well--on the microscale. Previous versions of the reactor attempted to mix bubbles of hydrogen gas and CO2 in liquid but no reduction occurred, possibly because the highly volatile hydrogen gas escaped before it had a chance to react. The solution came in discussions between Sojo and Hudson, who shared a lab bench at the RIKEN Center for Sustainable Resource Science in Saitama, Japan. The final reactor was built in Hudson's laboratory in Maine.

"Instead of bubbling the gases within the fluids before the reaction, the main innovation of the new reactor is that the fluids are driven by the gases themselves, so there is very little chance for them to escape," Hudson said.

The researchers used their design to combine hydrogen with CO2 to produce an organic molecule called formic acid (HCOOH). This synthetic process resembles the only known CO2-fixation pathway that does not require a supply of energy overall, called the Wood-Ljungdahl acetyl-CoA pathway. In turn, this process resembles reactions that might have taken place in ancient oceanic hydrothermal vents.

"The consequences extend far beyond our own biosphere," Sojo said. "Similar hydrothermal systems might exist today elsewhere in the solar system, most noticeably in Enceladus and Europa--moons of Saturn and Jupiter, respectively--and so predictably in other water-rocky worlds throughout the universe."

"Understanding how carbon dioxide can be reduced under mild geological conditions is important for evaluating the possibility of an origin of life on other worlds, which feeds into understanding how common or rare life may be in the universe," added Laurie Barge from NASA's Jet Propulsion Laboratory, an author on the study.

The researchers turned CO2 into organic molecules using relatively mild conditions, which means the findings may also have relevance for environmental chemistry. In the face of the ongoing climate crisis, there is an ongoing search for new methods of CO2 reduction.

"The results of this paper touch on multiple themes: from understanding the origins of metabolism, to the geochemistry that underpins the hydrogen and carbon cycles on Earth, and also to green chemistry applications, where the bio-geo-inspired work can help promote chemical reactions under mild conditions," added Shawn E. McGlynn, also an author of the study, based at the Tokyo Institute of Technology.

Credit: 
American Museum of Natural History

Skeletal study suggests at least 11 fish species are capable of walking

image: Thailand's cave angel fish, Cryptotora thamicola, is famous for its ability to walk, using a salamander-like gait. But it may not be alone: At least 10 relatives share its unusual pelvic shape.

Image: 
Zachary Randall/Florida Museum

GAINESVILLE, Fla. --- An international team of scientists has identified at least 11 species of fish suspected to have land-walking abilities.

The findings are based on CT scans and a new evolutionary map of the hillstream loach family, which includes the only living fish species caught in the act of walking: a rare, blind cavefish known as Cryptotora thamicola, or the cave angel fish. Pinpointing which species of hillstream loaches have walking capabilities can help scientists piece together how the first land-walking vertebrates might have come to be.

In a new study, researchers from the Florida Museum of Natural History, the New Jersey Institute of Technology, Louisiana State University and Maejo University in Thailand analyzed the bone structure of nearly 30 hillstream loach species, describing for the first time three categories of pelvic shapes. Based on the shape of the bone that connects some loaches' spines to their pelvic fins, the team found that 10 other species of loach shared the cave angel fish's unusually hefty pelvic girdle.

"Fishes don't usually have any connection between their spine and pelvic fin," said biologist Zachary Randall, manager of the Florida Museum's imaging lab and one of the study's co-authors. "But before, the idea was that the cave angel fish was totally unique. What's really cool about this paper is that it shows with high detail that robust pelvic girdles are more common than we thought in the hillstream loach family."

But not all loaches are so gifted: Though more than 100 species of hillstream loach are found throughout Southeast Asia, the cave angel fish is the only one whose walking capabilities have been observed and studied. Its salamander-like wiggle, powered by enlarged ribs bolstered with stabilizing muscle attachments, was first described in Scientific Reports in 2016 by Brooke Flammang, an assistant professor of biology at NJIT and the study's lead principal investigator.

Randall said the cave angel fish's walk is a key adaptation for surviving fast-flowing cave streams. It can grip rocky streambeds and move between habitats - even up waterfalls - as water levels fluctuate in the dry season. The cave angel fish's increased mobility could help it access well-oxygenated stream regions with few or no occupants. Still, little is known about the species, including what it eats.

"These loaches have converged on a structural requirement to support terrestrial walking not seen in other fishes," said study lead author and NJIT Ph.D. candidate Callie Crawford in a statement. "The relationships among these fishes suggest that the ability to adapt to fast-flowing rivers may be what was passed on genetically," rather than a set of specific physical characteristics.

The team used CT scanning and DNA analysis to trace the evolutionary history of the hillstream loach family and found that, rather than evolving from a single origin, a robust pelvic region appeared several times across the hillstream loach family.

"Even though the cave angel fish was first described in 1988, this is the first time it's been included in the hillstream loach family tree," Randall said. "With our Thai collaborators and using DNA analysis, we were able to use hundreds of genes to trace how pelvic shapes in these fish have evolved over time. Now, we have a much more accurate tree that adds a framework for studying how many species can walk and the extent to which they're able to."

"This study brought together a team of researchers with interests and levels of expertise that varied from those of us who do fieldwork and study fishes in their natural habitats to geneticists to comparative anatomists," added Lawrence Page, Florida Museum curator of fishes and a co-principal investigator of the study. "The result is a greatly improved understanding of the evolution of an extremely uncommon event - the ability of a fish to walk on land."

Randall and his team most recently observed the cave angel fish on a 2019 cave excursion in northwest Thailand. Given the rarity of spotting a cave angel fish in the field, Randall said the team was surprised to find six of them clinging to the bed of a fast-flowing shallow stream among glittering stalagmites in one of the cave's chambers. He added that the cave angel fish's rarity meant that museum specimens and CT data were key to mapping the family's evolution.

"The beauty of CT scanning is that you can capture different types of high-resolution data without compromising the integrity of the specimen," Randall said. "For rare species like this one, it even allows you to capture things that are hard to observe in the field, even what it eats."

The team published its work in the Journal of Morphology.

Credit: 
Florida Museum of Natural History

Data collection, sharing practices of apps played by young children

What The Study Did: Researchers investigated data collection and sharing practices of mobile apps played by preschool-age children and the associated sociodemographic characteristics of the children.

Authors: Jenny S. Radesky, M.D., of the University of Michigan Medical School in Ann Arbor, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2020.3345)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Suicide on screen: Getting the message right can support better mental health outcomes

13 Reasons Why is just one of several widely successful shows to hit our screens in recent years that contains portrayals of suicide, sparking concerns from experts about the potential impact on vulnerable viewers.

In a new paper, University of South Australia researchers have confirmed that portrayals of suicide in moving-image fiction and non-fiction media, such as television and web series, films, and documentaries, has the potential to increase suicidal ideation and behaviour.

But in the lead up to World Suicide Prevention Day on September 10, researchers Dr Miriam Posselt and Heather McIntyre say their research - which analysed the latest studies in suicide portrayal and screen media - also highlights the potential positive effects screen media can have.

"The research we reviewed shows there are many potential outcomes on viewers depending on how suicidal-related content is portrayed and engaged with but there is evidence that it can have a positive impact as well," Dr Posselt says.

"Screen media can increase suicide awareness and help-seeking behaviour, particularly if it includes support information or the character seeks help during their mental health challenges on screen and demonstrates managing or coping through a suicidal crisis.

"If used as an opportunity to educate, screen media could be a potentially powerful tool in suicide prevention, increasing awareness for mental health issues and reducing suicide shame and stigma.

"Television shows and movies can start conversations and share vital messages by helping to normalise the experience of having mental health difficulties and suicidal thoughts, as well normalising the act of reaching out to ask for help."

According to UniSA PhD candidate McIntyre, who has studied communications (film and media) and mental health, screen media has more potential to detrimentally affect viewers than other types of content.

"We live in a highly digitised world, where people have access to screens 24/7 and often 'binge-watch' through streaming services," McIntyre says.

"Film is a vehicle with far more immediacy than still images or the written word, which can create a far deeper sensory experience for the viewer, and therefore have a greater impact on them too.

"Filmmakers can push the boundaries of scintillation, possibly crossing over into an area that might not be helpful for a viewer's wellbeing.

"Research tells us that talking about suicide is not the problem - how it is portrayed is. Our review really demonstrates that the context and how images of suicide are presented, dictates whether it can have a negative or positive effect.

"At the same time, our review suggests a viewer's own past plays a part. Everyone engages with media differently. For individuals with higher levels (or history) of depression, suicidality, dissociation, thought suppression and identification with the protagonist, the potential harmful effects of viewing such media are often greater."

Given the potentially devastating impacts, clinical psychologist Dr Posselt believes filmmakers have a significant responsibility for their viewers' wellbeing.

"Filmmakers need to think deeply about what they include in their films, especially if they use graphic, sensationalist or dramatic depictions of suicide or self-harming behaviour, or depict these behaviours as solutions to problems," she says.

"Those involved in media production such as script-writers, producers and directors, should be aware of the potential harmful impacts that such portrayals can elicit, particularly because there are very rarely "trigger warnings" regarding this type of content in television and film.

"We know enough about how media portrayals of suicide can lead to suicide contagion and so called 'copy-cat suicides' that we should respect that and aim to prevent loss of life."

While traditional media guidelines on reporting on suicide have existed for many years - and last year the World Health Organisation introduced specific resources for filmmakers - Dr Posselt says all creators need to be more aware of how their products can affect mental health.

Credit: 
University of South Australia

Researchers show how mutations in DNA packaging machines cause cancer

image: Histology of a liver cancer that is deficient for ARID1A and ARID1B.

Image: 
UT Southwestern Medical Center

DALLAS - Sept. 7, 2020 - Like wrenches made of Legos, SWI/SNF chromatin remodeling complexes tighten or loosen DNA in our cells to control how genes are turned on and made into proteins. When assembled correctly, these complexes play a crucial role in the development of normal tissues, and when broken, they can lead to the development of cancer. These complexes are commonly disrupted by mutations in the genes that encode them - but how this leads to cancer is poorly understood.

New research from the Children's Medical Center Research Institute at UT Southwestern (CRI) determined how mutations in two key SWI/SNF proteins, ARID1A and ARID1B, can drive cancer development by disrupting the assembly of SWI/SNF complexes. The study, published in Nature Cancer, addresses fundamental questions about SWI/SNF biology as well as therapeutic strategies designed to kill cancer cells by targeting this complex.

"While it is abundantly clear that SWI/SNF components are defective in almost all cancer types, it is still fuzzy how mutations in components lead to broken SWI/SNF complexes, and how broken complexes cause disease," says study leader Hao Zhu, M.D., an associate professor at CRI. "In this study, we tried to cleanly break one important type of SWI/SNF complex to study how it falls apart, and how this leads to uncontrolled cancer growth."

SWI/SNF protein complexes help to pack and unpack DNA in the genome and are composed of 10-15 interacting proteins that can be arranged into different configurations in different tissues. Three main types of SWI/SNF complexes have been identified: cBAF, pBAF and ncBAF. But the roles they play in tissue development and disease have been unclear. To understand the importance of these complexes in animals, researchers at CRI focused on the cBAF complex. This complex was chosen because it is the most abundant one, and a subunit unique to this complex, ARID1A, is one of the most mutated genes in human cancer.

ARID1A is closely related to another protein known as ARID1B, which is also unique to cBAF. It has been shown that some cancer cells need at least one ARID1 protein to survive. To examine whether simultaneous loss of both ARID1A and ARID1B would be more likely to cause or kill cancer cells, researchers eliminated or knocked out both genes in mice. Strikingly, the loss of both ARID1A and ARID1B genes resulted in aggressive liver and skin cancer formation within weeks.

"In cancers where ARID1A is gone or mutated, one proposed strategy to stop cancer growth is to inhibit the replacement protein ARID1B. This method was predicted to kill cancer cells that might need cBAF function to survive," says Zhu. "However, our findings suggest that therapeutically targeting ARID1B could make matters worse by accelerating aggressive cancer development."

Researchers discovered that loss of these proteins led to the disassembly of the cBAF complex into many nonfunctional pieces.

They were able to uncover how ARID1A and ARID1B proteins maintain stabilizing connections between different components within cBAF complexes. This helped them pinpoint a number of important regions within these ARID1 proteins, that when mutated can make cBAF complexes fall apart. Interestingly, the importance of these regions also explains why mutations accumulate in these regions in human cancers. When cBAF falls apart, the leftover components interfere with the composition and function of other types of SWI/SNF complexes, which further contributes to cancer.

"We hope that the findings in our paper will change the way people think about the molecular consequences of SWI/SNF disruption and how mutations in this complex drive malignancy," says Zixi Wang, Ph.D., a postdoctoral researcher at CRI, assistant instructor of pediatrics at UTSW, and lead author of the paper.

Credit: 
UT Southwestern Medical Center

Researchers find unexpected electrical current that could stabilize fusion reactions

image: An artist's rendering of electrical current flowing through a tokamak fusion facility

Image: 
Elle Starkman / PPPL Office of Communications

Electric current is everywhere, from powering homes to controlling the plasma that fuels fusion reactions to possibly giving rise to vast cosmic magnetic fields. Now, scientists at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL) have found that electrical currents can form in ways not known before. The novel findings could give researchers greater ability to bring the fusion energy that drives the sun and stars to Earth.

"It's very important to understand which processes produce electrical currents in plasma and which phenomena could interfere with them," said Ian Ochs, graduate student in Princeton University's Program in Plasma Physics and lead author of a paper selected as a featured article in Physics of Plasmas. "They are the primary tool we use to control plasma in magnetic fusion research."

Fusion is the process that smashes together light elements in the form of plasma -- the hot, charged state of matter composed of free electrons and atomic nuclei -- generating massive amounts of energy. Scientists are seeking to replicate fusion for a virtually inexhaustible supply of power to generate electricity.

The unexpected currents arise in the plasma within doughnut-shaped fusion facilities known as tokamaks. The currents develop when a particular type of electromagnetic wave, such as those that radios and microwave ovens emit, forms spontaneously. These waves push some of the already-moving electrons, "which ride the wave like surfers on a surfboard," said Ochs.

But the frequencies of these waves matter. When the frequency is high, the wave causes some electrons to move forward and others backward. The two motions cancel each other out and no current occurs.

However, when the frequency is low, the waves pushes forward on the electrons and backward on the atomic nuclei, or ions, creating a net electrical current after all. Ochs found that researchers could surprisingly create these currents when the low-frequency wave was a particular type called an "ion acoustic wave" that resembles sound waves in air.

The significance of this finding extends from the relatively small scale of the laboratory to the vast scale of the cosmos. "There are magnetic fields throughout the universe on different scales, including the size of galaxies, and we don't really know how they got there," Ochs said. "The mechanism we discovered could have helped seed cosmic magnetic fields, and any new mechanisms that can produce magnetic fields are interesting to the astrophysics community."

The results from the pencil-and-paper calculations consist of mathematical expressions that give scientists the ability to calculate how these currents, which occur without electrons directly interacting, develop and grow. "The formulation of these expressions was not straightforward," Ochs said. "We had to condense the findings so they would be sufficiently clear and use simple expressions to capture the key physics."

The results deepen understanding of a basic physical phenomenon and were also unexpected. They appear to contradict the conventional notion that current drives require electron collisions, Ochs said.

"The question of whether waves can drive any current in plasma is actually very deep and goes to the fundamental interactions of waves in plasma," said Nathaniel Fisch, a coauthor of the paper, professor and associate chair of the Department of Astrophysical Sciences, and director of the Program in Plasma Physics. "What Ochs derived in masterful, didactic fashion, with mathematical rigor, was not only how these effects are sometimes balanced, but also how these effects sometimes conspire to allow the formation of net electrical currents."

These findings lay the groundwork for future research. "What especially excites me," Fisch said, "is that the mathematical formalism that Ochs has built, together with the physical intuitions and insights that he has acquired, now put him in a position either to challenge or to put on a firm foundation even more curious behavior in the interactions of waves with resonant particles in plasma."

Credit: 
DOE/Princeton Plasma Physics Laboratory

Post-COVID syndrome severely damages children's hearts

SAN ANTONIO, Texas, USA - Multisystem inflammatory syndrome in children (MIS-C), believed to be linked to COVID-19, damages the heart to such an extent that some children will need lifelong monitoring and interventions, said the senior author of a medical literature review published Sept. 4 in EClinicalMedicine, a journal of The Lancet.

Case studies also show MIS-C can strike seemingly healthy children without warning three or four weeks after asymptomatic infections, said Alvaro Moreira, MD, MSc, of The University of Texas Health Science Center at San Antonio. Dr. Moreira, a neonatologist, is an assistant professor of pediatrics in the university's Joe R. and Teresa Lozano Long School of Medicine.

"According to the literature, children did not need to exhibit the classic upper respiratory symptoms of COVID-19 to develop MIS-C, which is frightening," Dr. Moreira said. "Children might have no symptoms, no one knew they had the disease, and a few weeks later, they may develop this exaggerated inflammation in the body."

Results

The team reviewed 662 MIS-C cases reported worldwide between Jan. 1 and July 25. Among the findings:

71% of the children were admitted to the intensive care unit (ICU).

60% presented with shock.

Average length of stay in the hospital was 7.9 days.

100% had fever, 73.7% had abdominal pain or diarrhea, and 68.3% suffered vomiting.

90% had an echocardiogram (EKG) test and 54% of the results were abnormal.

22.2% of the children required mechanical ventilation.

4.4% required extracorporeal membrane oxygenation (ECMO).

11 children died.

"This is a new childhood disease that is believed to be associated with SARS-CoV-2," Dr. Moreira said. "It can be lethal because it affects multiple organ systems. Whether it be the heart and the lungs, the gastrointestinal system or the neurologic system, it has so many different faces that initially it was challenging for clinicians to understand."

The amount of inflammation in MIS-C surpasses two similar pediatric conditions, Kawasaki disease and toxic shock syndrome. "The saving grace is that treating these patients with therapies commonly used for Kawasaki - immunoglobulin and glucocorticosteroids - has been effective," Dr. Moreira said.

Cardiac abnormalities

Most of the 662 children suffered cardiac involvement as indicated by markers such as troponin, which is used with great accuracy in adults to diagnose heart attacks.

"Almost 90% of the children (581) underwent an echocardiogram because they had such a significant cardiac manifestation of the disease," Dr. Moreira said.

The damage included:

Dilation of coronary blood vessels, a phenomenon also seen in Kawasaki disease.

Depressed ejection fraction, indicating a reduced ability for the heart to pump oxygenated blood to the tissues of the body.

Almost 10% of children had an aneurysm of a coronary vessel. "This is a localized stretching or ballooning of the blood vessel that can be measured on an ultrasound of the heart," Dr. Moreira said.

Children with an aneurysm are at the most risk of a future event. "These are children who are going to require significant observation and follow-up with multiple ultrasounds to see if this is going to resolve or if this is something they will have for the rest of their lives," Dr. Moreira said.

"And that's catastrophic to a parent who had a previously healthy child and then he/she is in the very small percentage of individuals who developed MIS-C after COVID-19 infection," he said.

Another finding from the case studies: Almost half of patients who had MIS-C had an underlying medical condition, and of those, half of the individuals were obese or overweight.

"Generally, in both adults and children, we are seeing that patients who are obese will have a worse outcome," Dr. Moreira said.

When compared to the initial COVID-19 infection, inflammatory markers in MIS-C were far more abnormal. For instance, troponin, the marker used in adults to diagnose heart attacks, was 50 times its normal level in children with MIS-C.

"Evidence suggests that children with MIS-C have immense inflammation and potential tissue injury to the heart, and we will need to follow these children closely to understand what implications they may have in the long term," Dr. Moreira said.

Credit: 
University of Texas Health Science Center at San Antonio

How screen time and green time may affect youth psychological outcomes

image: Word cloud of the language used to conceptualise and measure ST and GT in the included studies (ST = 114 studies; GT = 58 studies; Both = 14 studies).

Image: 
Oswald TK, et al (2020); PLOS ONE, CC BY 4.0

Less screen time and more green time are associated with better psychological outcomes among children and adolescents, according to a study published September 4 in the open-access journal PLOS ONE by Tassia Oswald of the University of Adelaide, and colleagues.

The prevalence of mental illness among children and adolescents is increasing globally. Technological developments in recent decades have increased young people's engagement with screen-based technologies (screen time), and a reduction in young people's contact with nature (green time) has been observed concurrently. This combination of high screen time and low green time may affect mental health and well-being. But research investigating the psychological impacts of screen time or green time typically considers each factor in isolation and fails to delineate the reciprocal effects of high technology use and low contact with nature on mental health and cognitive outcomes. To address this question, Oswald and colleagues analyzed the findings of 186 studies to collate evidence assessing associations between screen time, green time, and psychological outcomes (including mental health, cognitive functioning, and academic achievement) for children and adolescents.

In general, high levels of screen time appeared to be associated with unfavorable psychological outcomes, while green time appeared to be associated with favorable psychological outcomes. Young people from low socioeconomic backgrounds were underrepresented in the literature overall and may be disproportionately affected by high screen time and low green time, making this a priority group for future research. However, additional longitudinal studies and RCTs are needed to determine whether decreasing screen time and increasing green time would improve psychological outcomes. According to the authors, preliminary evidence suggests that green time could potentially buffer the consequences of high screen time, meaning nature may be an under-utilized public health resource to promote youth psychological well-being in a high-tech era. Investment in more rigorous research is needed to explore this.

Oswald adds: "This systematic scoping review highlights that nature may currently be an under-utilised public health resource, which could potentially function as an upstream preventative and psychological well-being promotion intervention for children and adolescents in a high-tech era. However, robust evidence is needed to guide policies and recommendations around appropriate screen time and green time at critical life stages, to ultimately ensure optimal psychological well-being for young people."

Credit: 
PLOS