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INDIANAPOLIS -- In a new study, researchers from Regenstrief Institute, Indiana University School of Medicine and Indiana University Health provide insight into physician moral distress, a condition correlated with burnout and depression. The researchers report that about four of 10 doctors caring for older adult patients who require a surrogate decision-maker experienced moral distress.

As defined in the study, moral distress is an emotional experience in which an individual feels constrained from acting on deeply held beliefs, resulting in the sense of compromising one's professional integrity. Moral distress has been correlated with traumatic stress, burnout, depression and even intent to leave a position or profession.

When hospitalized older adults have impaired cognition, family members or other surrogates communicate with clinicians to provide information about the patient and to make medical decisions for them. When working with these surrogate decision makers, physicians often encounter ethical challenges - such as whether to continue life support or not - that may cause them to experience moral distress with its potential negative consequences.

"Making decisions for patients who can't participate in the decision-making process is hard for everyone and has a significant likelihood of causing physicians to experience moral distress," said study senior author Alexia Torke, M.D., associate professor of medicine at IU School of Medicine and Regenstrief Institute research scientist. "About half of older adults rely upon surrogate decision makers, so our findings that 42 percent of these doctors experience moral distress is a large and concerning number which, unless we address the issue, will likely grow as our population ages."

The study reported that physician moral distress occurred more frequently when (1) the physician was male; (2) the physician was an intern or other junior level doctor; (3) the patient was older; or (4) decisions were required about life-sustaining treatments.

The authors found that physicians were less likely to experience moral distress when (1) caring for patients residing in a nursing home; (2) the physician or family members had discussed care preferences with the patient before that individual became unable to make his or her own decisions; (3) the surrogate decision maker felt emotionally supported by the physician and other clinicians, and (4) whether or not the physician and surrogate decision maker agreed on the course of treatment.

"We learned that communication is clearly key to diminishing physician moral distress," said study corresponding author Lucia Wocial, PhD, R.N. a nurse ethicist. "Physician moral distress was lower when the patient had expressed his or her preferences through an advance medical directive or even orally to someone - a clinician, the surrogate or other family member or friend - before the patient was cognitively impaired and these preferences were made known to the treating physician." Dr. Wocial co-chairs the IU Health Ethics Consultation Service and is a faculty member of the Charles Warren Fairbanks Center for Medical Ethics at IU Health.

Dr. Torke added, "Since physician moral distress diminished when the patient's surrogate decision maker felt supported, efforts to forestall or decrease physician moral distress can focus on working with surrogates as well as the physicians themselves."

A total of 362 surrogate decision makers of older adult patients who lacked decisional capacity and 152 physicians carrying for these patients were surveyed for the study. The researchers found that a significant cause of physician moral distress was related to the feeling that the care plan included more life-sustaining treatment for the patient than the physician believed was appropriate.

A group led by scientists from the RIKEN Center for Integrative Medical Sciences (IMS) in Japan have developed a new method, RADICL-seq, which allows scientists to better understand how RNA interacts with the genome through chromatin--the structure in which the genome is organized.

There have been many changes in our understanding of the function of RNA in biology. Decades ago, it was generally believed that RNA functioned merely as an intermediary for the translation of DNA into proteins. However, the decoding of the human genome in the early 2000s led to the realization that a large amount of RNA--known as "junk" at the time--did not code proteins. Subsequent work on large-scale genomic projects such as ENCODE and RIKEN-led FANTOM found that there were large numbers of long non-protein coding RNAs in the mammalian genome, which interact with the DNA. Many of these RNAs are found in the cell nucleus, and are attached to chromatin, the structure used to tightly fold the DNA. However, it is still not clear exactly what RNAs interact with which regions of the DNA in different cells.

To achieve a better understanding of these interactions, and to determine whether RNA is actually a part of the chromatin structure, the scientists developed a new technology, which they called RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), which maps genome-wide RNA-chromatin interactions in intact nuclei. This technology, published in Nature Communications, allows researchers to identify distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA-chromatin interactions, and emphasizes the role of transcription in the establishment of chromatin structure.

To test the validity of the method, the scientists looked at two non-coding RNAs which are known to be expressed preferentially in certain cell types. The first, known at NEAT1, may be involved in the structure as it is associated with a mysterious structure known as paraspeckles found in mammalian cell nuclei. The second, Fgfr2, is involved in embryonic development and tissue repair, especially for bone and blood vessels. They found that in mouse embryonic stem cells--an early type of cell--that NEAT1 acts almost exclusively on genomic regions of chromosome 19, from which it itself derives from, whereas in oligodendrocyte progenitor cells--a later type of developmental cell that can differentiate into brain cells--it interacts with a broad range of genomic regions on other chromosomes as well. Fgfr2, by contrast, mostly interacts with genomic regions on its own chromosome.

"This study is a first step toward understanding how the interplay between RNA and chromatin ensures proper genome function. Our data indicate that RNAs may exert more widespread effects on gene regulation and chromatin organization than previously thought," says Alessandro Bonetti, one of the corresponding authors of the study.

"The broad, genome-wide applications of this technology will help us to understand the fundamental role of non-coding RNA as a regulator of genome activity, which could lead to future applications and therapies" says Piero Carninci, one of the senior authors of the study.

Researchers at Tel Aviv University (TAU) have discovered a non-oxygen breathing animal. The unexpected finding changes one of science's assumptions about the animal world.

A study on the finding was published on February 25 in PNAS by TAU researchers led by Prof. Dorothee Huchon of the School of Zoology at TAU's Faculty of Life Sciences and Steinhardt Museum of Natural History.

The tiny, less than 10-celled parasite Henneguya salminicola lives in salmon muscle. As it evolved, the animal, which is a myxozoan relative of jellyfish and corals, gave up breathing and consuming oxygen to produce energy.

"Aerobic respiration was thought to be ubiquitous in animals, but now we confirmed that this is not the case," Prof. Huchon explains. "Our discovery shows that evolution can go in strange directions. Aerobic respiration is a major source of energy, and yet we found an animal that gave up this critical pathway."

Some other organisms like fungi, amoebas or ciliate lineages in anaerobic environments have lost the ability to breathe over time. The new study demonstrates that the same can happen to an animal -- possibly because the parasite happens to live in an anaerobic environment.

Its genome was sequenced, along with those of other myxozoan fish parasites, as part of research supported by the U.S.-Israel Binational Science Foundation and conducted with Prof. Paulyn Cartwright of the University of Kansas, and Prof. Jerri Bartholomew and Dr. Stephen Atkinson of Oregon State University.

The parasite's anaerobic nature was an accidental discovery. While assembling the Henneguya genome, Prof. Huchon found that it did not include a mitochondrial genome. The mitochondria is the powerhouse of the cell where oxygen is captured to make energy, so its absence indicated that the animal was not breathing oxygen.

Until the new discovery, there was debate regarding the possibility that organisms belonging to the animal kingdom could survive in anaerobic environments. The assumption that all animals are breathing oxygen was based, among other things, on the fact that animals are multicellular, highly developed organisms, which first appeared on Earth when oxygen levels rose.

"It's not yet clear to us how the parasite generates energy," Prof. Huchon says. "It may be drawing it from the surrounding fish cells, or it may have a different type of respiration such as oxygen-free breathing, which typically characterizes anaerobic non-animal organisms."

According to Prof. Huchon, the discovery bears enormous significance for evolutionary research.

"It is generally thought that during evolution, organisms become more and more complex, and that simple single-celled or few-celled organisms are the ancestors of complex organisms," she concludes. "But here, right before us, is an animal whose evolutionary process is the opposite. Living in an oxygen-free environment, it has shed unnecessary genes responsible for aerobic respiration and become an even simpler organism."

ARLINGTON HEIGHTS, IL - (FEBRUARY 25, 2020) - A new article in Annals of Allergy, Asthma and Immunology, the scientific journal of the American College of Allergy, Asthma and Immunology (ACAAI) discusses the difficulties faced by parents of children with food allergies in not transferring their own anxieties to their children.

"Food allergies are scary for both parents and children, which is why it's important for parents to offer fact-based strategies in order to not increase their child's concerns" says researcher Lisa Lombard, PhD, lead author of the article. "According to the allergists we interviewed, thoughtful and balanced communication and having credible information to share with your child go a long way toward helping your child with food allergies cope with their fears."

Researchers conducted interviews with six board-certified allergists who treat a high volume of children with food allergies. The goal of the interviews was, in part, to get the allergists' perspectives on the major factors contributing to elevated anxiety in food allergic patients.

"The allergists said the major factors contributing to elevated anxiety in kids with food allergies included fear of the epinephrine auto-injector needle, fear of anaphylaxis and apprehension about participating in oral food challenges or oral immunotherapy," said Ruchi Gupta, MD, ACAAI member and study co-author. "They also said that although allergic reactions and epinephrine can be scary and disruptive, those experiences were often opportunities for positive coping. For example, successfully using epinephrine can bring a sense of relief after the unknown is faced."

The allergists noted that with younger children in particular, the child might not be especially anxious, but the parents are. They also said that food challenges - where small amounts of a food a child might be allergic to are introduced in increasingly larger amounts - are an opportunity for families to lessen their fear of the unknown.

"Because children take cues from their parents, and their level of anxiety often reflects their parents' level of anxiety, parents need to recognize how they're communicating with their children about food allergies," says Dr. Gupta. "The allergists interviewed told us they sometimes have parents come in for counseling without the child because doing so helps them take care of the child and the family at the same time. One allergist suggested parents use reassuring dialogue like 'we'll get through this' with their kids rather than expressing their own anxiety of fear."

Intake of dairy milk is associated with a greater risk of breast cancer in women, according to a new study conducted by researchers at Loma Linda University Health.

Dairy, soy and risk of breast cancer: Those confounded milks, published in the International Journal of Epidemiology, found that even relatively moderate amounts of dairy milk consumption can increase women's risk of breast cancer -- up to 80% depending on the amount consumed.

First author of the paper, Gary E. Fraser, MBChB, PhD, said the observational study gives "fairly strong evidence that either dairy milk or some other factor closely related to drinking dairy milk is a cause of breast cancer in women.

"Consuming as little as 1/4 to 1/3 cup of dairy milk per day was associated with an increased risk of breast cancer of 30%," Fraser said. "By drinking up to one cup per day, the associated risk went up to 50%, and for those drinking two to three cups per day, the risk increased further to 70% to 80%."

Current U.S. Dietary guidelines recommend three cups of milk per day. "Evidence from this study suggests that people should view that recommendation with caution," Fraser said.

Dietary intakes of nearly 53,000 North American women were evaluated for the study, all of whom were initially free of cancer and were followed for nearly eight years. Dietary intakes were estimated from food frequency questionnaires (FFQ), also repeated 24 hour recalls, and a baseline questionnaire had questions about demographics, family history of breast cancer, physical activity, alcohol consumption, hormonal and other medication use, breast cancer screening, and reproductive and gynecological history.

By the end of the study period, there were 1,057 new breast cancer cases during follow-up. No clear associations were found between soy products and breast cancer, independent of dairy. But, when compared to low or no milk consumption, higher intakes of dairy calories and dairy milk were associated with greater risk of breast cancer, independent of soy intake. Fraser noted that the results had minimal variation when comparing intake of full fat versus reduced or nonfat milks; there were no important associations noted with cheese and yogurt.

"However," he said, "dairy foods, especially milk, were associated with increased risk, and the data predicted a marked reduction in risk associated with substituting soymilk for dairy milk. This raises the possibility that dairy-alternate milks may be an optimal choice."

A hazardous effect of dairy is consistent with the recent AHS-2 report suggesting that vegans but not lacto-ovo-vegetarians experienced less breast cancer than non-vegetarians.

Fraser said the possible reasons for these associations between breast cancer and dairy milk may be the sex hormone content of dairy milk, as the cows are of course lactating, and often about 75% of the dairy herd is pregnant. Breast cancer in women is a hormone-responsive cancer. Further, intake of dairy and other animal proteins in some reports is also associated with higher blood levels of a hormone, insulin-like growth factor-1 (IGF-1), which is thought to promote certain cancers.

"Dairy milk does have some positive nutritional qualities," Fraser said, "but these need to be balanced against other possible, less helpful effects. This work suggests the urgent need for further research."

In the last decade there has been rapid expansion in the area of ocean designated as a Marine Protected Area (MPA).

Despite this progress, marine biodiversity continues to decline, placing at risk the health of our oceans and the critical role the oceans have in supporting human well-being.

Now a team of marine scientists from across the UK, led by the Marine Conservation Research Group at the University of Plymouth, has called on the Government to increase its ambition to save the oceans by overhauling its approach to marine conservation management.

The researchers have worked at the sharp end of conservation and fisheries management for several decades, and draw on their research and wider expertise to make four key recommendations to Government ministers. They are:

Enable the repair and renewal of marine habitats rather than managing degraded or altered habitats in their reduced state;

Unite conservation policy and fisheries management as the two are critically dependent on each other rather than competing interests;

Establish improved processes for understanding the benefits from ocean protection in a format that leaves in no doubt the links between ocean protection and human lives and livelihoods;

Develop a smarter approach to managing the health of the entire ocean that moves beyond MPAs and enables links to be made across sectors towards sustainability.

The recommendations are published in the journal Marine Policy, and scientists say addressing these issues would enable the UK it to meet its target of becoming a global leader in fisheries management and marine conservation.

Dr Sian Rees, Senior Research Fellow in the University's School of Biological and Marine Sciences and the paper's lead author, said: "2020 is a critical year for ocean protection as we build towards the UN Decade of Ocean Science, and a year where Governments have been invited to step up and support action to halt the global decline in marine biodiversity. In this 'super year' for the ocean it is within the gift of UK Government to set an increased ambition for ocean conservation. This would support the Governments ambition to be 'the first generation that leaves the environment in a better state than that in which we inherited it' and establish the UK as a global leader in fisheries management and marine conservation."

Dr Bryce Beukers-Stewart, from the Department of Environment and Geography at the University of York, added: "There is now substantial evidence that well managed and strategically placed marine protected areas (MPAs) can provide benefits for not only conservation, but also fisheries and human well-being. Unfortunately, many of the MPAs around the UK are not currently managed in a way that delivers their full potential. It is also important that MPAs become better integrated with other marine management measures, if we really want to ensure the long-term future of the benefits provided to us by the ocean."

Jean-Luc Solandt, Principal Specialist in MPAs at the Marine Conservation Society, said: "There has been good progress between many people and organisations to bring effective management for our seas, but this is not enough. More resources and focus on recovery of entire ecosystems has not been forthcoming and we are making the case for stricter management over wider areas of our MPAs."

WEST LAFAYETTE, Ind. - A new device to help homeowners cut electricity bills could also provide more efficient and safer cooling options for companies and vehicles.

Purdue University researchers developed their device to decrease energy consumption of the vapor-compression heat pump cycle, which is commonly used in homes, businesses and vehicles for cooling and heating.

The team created a novel turbomachine expander that helps harvest previously wasted energy used in the process of moving the air from high to low pressure. The device can be used as a control agent within an existing heat pump. The team's work is presented in the International Journal of Refrigeration.

"Our solution packs a two-fold punch in that it's more efficient but still just as safe as conventional vapor-compression heat pump cycle operations," said Riley Barta, a graduate research assistant in Purdue's College of Engineering. "We created a device that's the best of both worlds with a fixed nozzle and variable options for phase separation that allow a much broader range of applications than are possible with more conventional approaches."

The other members of the Purdue team are Eckhard Groll, the Reilly Professor of Mechanical Engineering and director of the Office of Professional Practice, and David Ziviani, a research assistant professor of engineering.

"Not only does our device help cut down wasted energy, which helps reduce electricity costs and improve efficiency, but it works across a range of ambient conditions," Barta said. "Our expander and control method ensure the safe operation of the heat pump system."

The Purdue device can be used with any common heating and cooling systems found in homes, vehicles and industrial buildings.

The innovators are working with the Purdue Research Foundation Office of Technology Commercialization to patent the technology. The office recently moved into the Convergence Center for Innovation and Collaboration in Discovery Park District, located on the west side of the Purdue campus.

(San Antonio, TX -- Feb. 25, 2020) Researchers at The University of Texas at San Antonio (UTSA) identified the best approach to help children operate Augmented Reality (AR). According to UTSA computer science experts, a major barrier into wider adoption of the technology for experiential learning is based on AR designs geared toward adults that rely on voice or gesture commands. By conducting in-classroom testing among elementary school students, UTSA researchers uncovered that AR programs are best delivered using controller commands, followed by programs that communicate with age-specific language.

"The majority of AR programs urge users to speak commands such as 'select' but a child doesn't necessarily communicate in this manner. We have to create AR experiences that are designed with a child in mind. It's about making experiential learning grow and adapt with the intended user," said John Quarles, co-author and associate professor in the UTSA Department of Computer Science. "Currently, many voice commands are built to recognize adult voices but not children."

Quarles, along with Brita Munsinger, co-lead on the project, designed the research study to replace more complex word instructions with easier commands that would be best understood by the younger subjects. This allowed the children to reduce time and error in completing a series of tasks.

"One of my favorite parts of working in human-computer interaction is the impact your work can have. Any time someone uses technology, there's an opportunity to improve how they interact with it," said Munsinger. "With this project, we hope to eventually make augmented reality a useful tool for teaching STEM subjects to kids."

The UTSA study was conducted in classrooms with children ages 9 -11 who wore Microsoft HoloLens and were then asked to complete a series of tasks. In the analysis, students by far exhibited less error, fatigue and higher usability when interaction with AR was based on completing tasks that relied on hardware controllers. Voice and gesture selection both took longer than controller selection. Children fatigue levels also were highest when participants had to make gesture commands. Moreover, this modality was the least usable interaction, while controller was rated highest on usability.

According to a 2019 Deloitte report on the state of AR, investments into this segment of digital reality will be led by the U.S. and estimated over $3.5 billion. The University of Texas at San Antonio is dedicated to the advancement of knowledge through research and discovery, teaching and learning, community engagement and public service. Currently Quarles serves as director of San Antonio Virtual Environments Lab (SAVE). His areas of focus include Human-Computer Interaction Virtual, Augmented, and Mixed Realities. He has developed virtual reality programs for children with learning disabilities.

"We hope that with this study will serve as a launching point to improve the future immersive learning tools in our classrooms," said Quarles.

Social media smarts could make you less susceptible to skin cancer as new research shows that media literacy skills can help change people's attitudes about what is believed to be the 'tanned ideal'.

Conducted by the University of South Australia, the research tested the ability of social media to influence people's perceptions of tanning, finding that the greater an individual's ability to critically access and evaluate social media posts, the less likely they were to idealise a golden tan.

The world-first study found that individuals with higher media literacy capabilities were much less likely to embrace or compare themselves to a tanned ideal, yet the opposite was true for those with fewer media literacy skills.

Lead researcher, UniSA's Dr John Mingoia, says the findings highlight the importance of incorporating media literacy into sun safe education initiatives.

"The desire for tanned skin has long been part of Australian culture, yet despite everything we know about the dangers of tanning and the risk of skin cancer, people are still engaging in unsafe sun behaviour in the quest for what they consider a healthy golden glow," Dr Mingoia says.

"In Australia, where we're exposed to some of the highest levels of UV radiation in the world (and correspondingly, have one of the highest rates of skin cancer in the world), the desire for tanned skin is undeniably dangerous.

"The challenge is that people are exposed to images of the 'tanned ideal' on social media platforms - Instagram, Facebook, Snapchat and YouTube - where their perceptions of attractiveness are shaped and reinforced by images from advertisers, influencers, bloggers, and friends, many of which have been artificially enhanced or manipulated.

"It's this kind of everyday organic content that we're trying to combat, so that young adults can more easily identify the pervasive way that social media can influence their knowledge, attitudes and behaviours.

"Adding such media literacy skills to Australia's existing and well-developed sun safe messages and campaigns will help individuals better manage their responses to media exposure, and importantly reduce any potentially negative self-comparisons."

Skin cancer is the most common cancer worldwide, with 2-3 million non-melanoma skin cancers and 132,000 melanoma skin cancers occurring each year. In Australia, approximately, two in three Australian will be diagnosed with skin cancer by the time they are 70.

The study tested the responses of 151 young Australian adults (61 male and 90 females, aged 18-29) after exposure to a series of social media posts that featured either tanned or paler-skinned models. The most common skin type in the study was Fitzpatrick skin Type III (45 per cent) - people whose skin reacts to the sun by possibly freckling, burning on occasion, and sometimes tanning. Media literacy was assessed using the Media Attitudes Questionnaire (MAQ), a Likert-type ranking scale, that was adapted to test media literacy in relation to the tanned ideal.

The study showed that, on average, participants used social media for close to 173 minutes (three hours) a day, splitting their time between Facebook (96.7 per cent), YouTube (84.8 per cent), Instagram (69.5 per cent) and SnapChat (69.5 per cent).

Dr Mingoia says that social media presents additional barriers to healthy sun behaviours.

"Increasing people's knowledge of how social media messages are constructed, manipulated and altered, as well as their capacity to impact cognition and attitudes, will improve awareness and scepticism of content on social media," Dr Mingoia says.

"What we're looking to do is add a complementary layer to existing sun safe education which we hope will lead to a reduced acceptance of what people see relating to tanned ideals on social media and consequently, better health outcomes.

"With more than 90 per cent of young adults regularly using social media, it's a space we cannot afford to overlook in the battle to combat skin cancer."

When neutrinos crash into water molecules in the billion-plus tons of ice that make up the detector at the IceCube Neutrino Observatory in Antarctica, more than 5,000 sensors detect the light of subatomic particles produced by the collisions. But as one might expect, these grand-scale experiments don't come cheap.

In a paper recently accepted by Physical Review Letters, an international team of physicists working at the Department of Energy's SLAC National Accelerator Laboratory demonstrated an inexpensive way to expand IceCube's neutrino search.

The researchers directed an electron beam diverted from SLAC's Linac Coherent Light Source (LCLS) into a large block of plastic to mimic neutrinos colliding with ice. When a neutrino interacts with ice, it produces a cascade of high-energy particles that leave a trail of ionization in their wake. The same is true for electron collisions in the plastic.

To detect those ionization trails, the team used an antenna to bounce radio waves off them. This created radar echoes that were picked up by additional antennas. It was the first time researchers have been able to detect radar echoes from a particle cascade.

These echoes carry information about neutrinos in an energy range that could bridge the gap between the lower-energy neutrinos that IceCube detects and the higher-energy neutrinos detected by other in-ice and balloon-based detectors. To follow up, the researchers hope to use a similar set-up to detect neutrinos with a radio echo in Antarctic ice. If successful, the technique could eventually allow researchers to expand the energy reach of IceCube without breaking the bank.

All life is challenged by oxidants -- reactive molecules or compounds that remove electrons from other molecules -- often with adverse effect, commonly referred to as oxidative stress. Consequently, all organisms have evolved specialized antioxidant defenses. In humans and other multicellular animals, that defense depends upon a protein called NRF2 and its inhibitor, KEAP1.

In a new study, published February 24, 2020 in the Journal of Hepatology, a team of scientists, led by postdoctoral fellows Feng He, PhD, and Laura Antonucci, PhD, and senior author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at University of California San Diego School of Medicine, suggest prolonged exposure to NRF2 and KEAP1 may contribute to enlargement of the liver and fatty liver diseases.

NRF2 (Nuclear factor erythroid 2-related factor 2) is the master regulator of the antioxidant response. When cells are healthy and unstressed by oxidants, levels of NRF2 are kept low by KEAP1 (Kelch-like ECH-associated protein 1), which is constantly degrading NRF2.

But in response to oxidative stress, KEAP1 is inactivated, releasing NRF2 from its inhibitory grip. NRF2 levels subsequently build within the cell with the protein entering the nucleus, where it stimulates expression of numerous genes that code for enzymes and other proteins that detoxify harmful oxidants.

"By being able to reduce the devastating impact of oxidative stress, the KEAP1-NRF2 system has long been thought to protect us from cancer and aging," said Karin. "And much effort has been dedicated to the development of NRF2 activators for cancer prevention and age-related diseases. Many such compounds are being sold at health food stores as anti-aging remedies."

But research in recent years has found that several cancers, including liver and lung cancers, harbor mutations that decouple NRF2 from KEAP1, suggesting that persistent NRF2 activation may not be such a good thing after all. Some researchers now believe cancer cells may actually use NRF2 to protect themselves from radiation and chemotherapeutics.

Using a new mouse model whose liver cells express a KEAP1-resistant form of NRF2, Karin and collaborators found that persistent activation of NRF2 in these mice resulted in rapid and dramatic enlargement of the liver, known as hepatomegaly. In humans, hepatomegaly can appear after insulin overdosing, exposure to various toxins, certain viral and bacterial infections or as an indicator of an underlying disease, such as cirrhosis and liver cancer.

Because NRF2-induced hepatomegaly is similar to insulin-induced hepatomegaly, which relies upon activation of a protein kinase called AKT, the research team investigated the involvement of insulin and AKT in NRF2-induced hepatomegaly.

Although no evidence for excessive insulin production was uncovered, the scientists found that AKT (otherwise known as Protein kinase B) was activated in livers expressing the degradation-resistant form of NRF2. The scientists also discovered that inhibiting AKT produced complete reversal of hepatomegaly and rapid restoration of normal liver size and physiology in the mice. And that chronic NRF2 activation causes persistent production of growth factors that activate AKT.

Working with co-corresponding author Beicheng Sun, MD, a liver surgeon at Nanjing University Medical School in China, the team also reported that human hepatomegaly that is caused by either toxin exposure or autoimmune hepatitis also entails NRF2 activation, enhanced growth factor signaling and stimulation of AKT activity.

In addition to liver enlargement, the scientists said persistent NRF2 activation produced excessive fat and glycogen accumulation, suggesting that NRF2 may also be involved in fatty liver disease, such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis -- common metabolic disorders affecting millions of Americans.

The new findings, said Karin, suggest that AKT inhibitors, some of which have already been evaluated in humans for their anti-cancer activity, may be effective in the treatment and reversal of hepatomegaly, which affects more than 200 million persons worldwide.

Oak Brook, IL - The March edition of SLAS Discovery features the cover article, "CRISPR: A Screener's Guide," by Carlos le Sage, Ph.D., Steffen Lawo, Ph.D., and Benedict C.S. Cross, Ph.D., (Horizon Discovery, United Kingdom). In their review, the authors discuss how CRISPR-Cas9 systems are being used widely throughout the drug discovery process and the development of new precision medicines.

The discovery of CRISPR-Cas9 systems has helped ignite gene editing adoption and has greatly impacted pharmaceutical and biotechnology research. Because of the CRISPR-Cas9 discovery, gene editing can be used at an industrial scale to identify and validate new biological targets for precision medicines, with functional genomic screening also having an increasingly important role. CRISPR screens provide more robust data sets for target identification and validation, and identify potential mechanisms of drug resistance and sensitivity ahead of new drugs entering clinical trials.

The March cover article also examines the developing landscape for CRISPR screening technologies within the pharmaceutical industry and explores the next steps for this constantly evolving screening platform.

Coral reefs are not doomed. Although human activities threaten the iconic ecosystems in many different ways, scientists maintain that reefs can continue to thrive with the right assistance.

A study by researchers at UC Santa Barbara details how reducing nutrient pollution can help prevent coral from bleaching during moderate heatwaves. The results, which appear in the journal Proceedings of the National Academy of Sciences, offer new strategies for managing these highly threatened yet important ecosystems.

Reef-building corals host beneficial algae within their tissues. In exchange for protection and nitrogen, the algae provide the coral with sugars. All is well until the water gets too warm.

At higher temperatures, the algae's photosynthesis goes into overdrive, and the chemical balance between the coral and the algae breaks down. At a certain point, the coral ejects its tenant in a process known as bleaching. Coral can survive for a time without their algae, so recovery is possible if conditions return to normal quickly. But in the absence of its partner the coral will eventually die, and the worse the bleaching is, the more likely that is to happen.

Experiments in the lab, as well as a few small field studies, began to suggest to researchers that nitrogen pollution, such as from fertilizer and sewage runoff, could exacerbate bleaching. Excess nitrogen in the water can short-circuit the beneficial partnership between corals and the algae. However, until now, it was not known if nutrient effects on bleaching occurred in many corals over large areas.

The UC Santa Barbara scientists decided to investigate the effects of nitrogen on coral bleaching -- on the scale of an entire island -- as part of their long-term ecological research project on the island of Moorea in French Polynesia.

The team surveyed more than 10,000 corals around Moorea during a moderate heatwave in 2016. They studied individual coral colonies in different habitats to capture the variability at a high resolution across the island as a whole. Since nitrogen concentrations naturally fluctuate in seawater, the researchers took samples from Turbinaria ornata, a large alga common on the reefs around Moorea. This provided a record of the nitrogen available to corals in the months leading up to the heatwave.

"These relationships are very complex," said lead author Mary Donovan, a postdoctoral researcher at the university's Marine Science Institute. "So, studying them at spatial and temporal scales that match those happening in nature is critical to revealing these really important interactions."

The team found that high levels of nitrogen pollution lowered the temperature at which coral began to bleach. It also increased the severity of bleaching. "It basically doubles how severe the bleaching is," said Russ Schmitt, a professor in the Department of Ecology, Evolution, and Marine Biology (EEMB). Coral bleached at extreme temperatures regardless of how much nitrogen was in the system, but even a little excess nitrogen could tip the scale toward severe bleaching under moderate heat conditions.

The scientists looked at the two most common types of branching coral in Moorea. They expected them to respond differently to nutrient pollution, since one is more sensitive to temperature stress than the other. However, both types of corals showed identical responses. This suggested that the strong effect nitrogen pollution has on coral at temperatures normally below levels that trigger bleaching may apply broadly to many coral species.

Climate change has increased the strength and frequency of marine heatwaves, which has increased the severity of bleaching, according to the researchers. Coral reefs are at a tipping point, they explained, so every strategy available to encourage reef health and resilience needs to be explored. "This study shows that it is possible to take some local actions such as reducing nutrient pollution to give reefs a chance, at least in the near term," said coauthor Sally Holbrook, also a professor in EEMB.

The researchers plan to continue investigating how the effect of nutrient pollution on bleaching translates into coral mortality. The team conducted a similar survey in 2019, a year that saw some of the highest water temperatures on record around the island of Moorea. Their findings should offer a better account of longer-term effects nutrient pollution has on coral reef ecosystems.

"Marine heatwaves and coral bleaching are the defining challenge facing coral reefs in the 21st century," said coauthor Deron Burkepile, a professor in EEMB. "Managing CO2 emissions requires global action, so as ecologists and conservationists, we're are also looking for levers we can pull at the local scale to help coral reef ecosystems withstand these global stressors while we also take action to address climate change."

SASKATOON--University of Saskatchewan (USask) researchers have used a novel combination of techniques to compare the effects of two families of pesticides used in agriculture, and found that at low dosages the newer pesticide is less toxic than a currently used neonicotinoid one.

USask biology professor Jack Gray's research on locusts, published in the Proceedings of the National Academy of Sciences (PNAS), may have implications for understanding the link between these pesticides and mortality in other species such as the "colony collapse disorder" responsible for the deaths of millions of bees worldwide.

"There is controversy over neonicotinoid pesticides," said Gray. "Their development suggested they were safer than other pesticides, but it is more complicated because their effects at non-lethal doses on insects and other species needed to be investigated further."

From his previous studies with locusts, Gray designed a virtual flight simulator where he tested how non-lethal doses of pesticides can affect the insects' ability to visually detect moving objects such as trees and predators. He and his team found that the newer sulfoxamine pesticide, sulfoxaflor (SFX), does not impair the insects' motion detection ability, while the current neonicotinoid imidacloprid (IMD) does.

"Even though this suggests that SFX isn't as toxic as the other pesticide at low dosages, more testing is needed to establish whether it a safer, preferable option for agriculture use," said Gray.

Gray and his team used an approach that looks at behaviour and neurophysiology, which have seldom been applied together for studying pesticide effects.

The results confirmed that IMD had negative effects on the locusts' ability to jump and escape dangers, while SFX did not. A potential explanation may be that SFX does not bind as strongly to the same receptor that determines the insects' sensitivity to the pesticides.

The USask team chose locusts because their nervous system is well studied, and the neurons that regulate their motion detection are common to a variety of other species including birds, and likely even humans.

"These findings may be applicable to other species to understand how these pesticides affect how fast the nervous system can send information," said Gray.

By using small electrodes in the insect's thorax, former USask PhD student Rachel Parkinson, first author of the paper, measured the electrical signals directly from a neuron in the insect's nervous system that detects visual motion and controls flight.

"The reaction time of locusts treated with the IMD pesticide slows down, impairing their ability to avoid objects," said Parkinson, now a post-doctoral fellow at the University of Oxford. The USask team also includes PhD student Sinan Zhang.

Targeting overactive immune cells and dampening their chronic neurotoxic effects may offer new therapeutic strategies for traumatic brain injury (TBI), according to new preclinical research in mice, which has been published today [Monday 24th February 2020] in the Journal of Neuroscience.

The collaborative research, which involved scientists from Trinity College Dublin and the University of Maryland School of Medicine, Baltimore, USA, also suggests that the impact of TBI on brain degeneration may be modifiable a relatively long time after the injury was sustained - something at odds with current thinking.

Traumatic brain injury and delayed treatment

Triggered by trauma, microglia - the brain's immune cells - morph into an inflammatory state, which helps to protect the brain. However, long-term inflammation after TBI may contribute to neurological degeneration and cognitive declines similar to those observed in TBI-associated neurodegenerative diseases, such as chronic traumatic encephalopathy and Alzheimer's disease.

The scientists involved in the new study found that highly delayed targeting of chronic inflammation pathways may be a very effective therapeutic strategy for TBI.

One month after a TBI, the team inhibited a particular receptor microglia need to survive. The inhibition killed 95% of the mice microglia cells. However, the cells bounced back to normal levels once the inhibition ends.

The researchers then stopped the inhibition after one week and let the mice recover for a few months. They found that the inhibition essentially "reset" the mice's microglia: the new cells were in a more normal, less inflammatory state. The mice recovered better than the mice that didn't receive treatment, showing less brain damage, fewer neuron deaths, and better motor and cognitive performance.

David Loane, Research assistant professor in Trinity's School of Biochemistry and Immunology, said:

"These preclinical studies suggest that the consequences of TBI on brain degeneration and related neurological impairment may be modifiable quite a long time after injury by targeting inflammation pathways, which is a finding at odds with widely accepted views about head injury."

"The exciting thing is the possibility that we may one day be able to minimise brain degeneration and neurological impairment in people who have suffered a TBI. It will of course always be incredibly important to act quickly whenever someone suffers a TBI, but our findings suggest targeting inflammation pathways further down the treatment line may make a major difference to long-term brain health and recovery."

Dr Loane has recently established a state-of-the-art, preclinical research laboratory in Trinity to study the neuroimmunology of TBI and related dementias. His work is supported by an SFI President of Ireland Future Research Leaders Award and the National Institutes of Health (USA).