Culture

What The Study Did: One-third of COVID-19 patients from Hubei, China, had ocular manifestations, occurring frequently in patients with more severe physical conditions.

Authors: Liang Liang, M.D., of China Three Gorges University in Yichang, China, and Kaili Wu, M.D.,  of Sun Yat-sen University Guangzhou, China, are the corresponding authors.

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(doi:10.1001/jamaophthalmol.2020.1291)

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What The Viewpoint Says: Lessons learned from the 2003 severe acute respiratory syndrome (SARS) epidemic may help reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), the cause of coronavirus disease 2019 (COVID-19), to health care workers performing open tracheostomies, a surgical procedure to open an airway that may be required for many patients with COVID-19.

Authors: Woei Shyang Loh, M.B.B.S., of the National University of Singapore, is the corresponding author.

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(doi:10.1001/jamaoto.2020.0764)

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What The Study Did: Health care workers who come in close contact with a patient's head and neck are particularly at risk for developing coronavirus disease 2019 (COVID-19) because of the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) through respiratory droplets. This article provides safety recommendations for these health care workers regarding exams and surgical procedures based on a review of the literature and the experiences of physicians with firsthand knowledge of safety procedures during this pandemic.

Authors: Babak Givi, M.D., of NYU Langone Health in New York, is the corresponding author.

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(doi:10.1001/jamaoto.2020.0780)

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Visual feedback is just as important as a sense of body position when it comes to the involuntary reflexes that activate muscle movement, says a new study in the open-access journal eLife.

The findings provide insights into how the brain balances different types of sensory information to control the earliest stages of movement, adding to our understanding of how these processes are controlled in health and disease.

Throughout daily life, we alter our body movements in response to changing cues. For example, when reaching for a target object our brain uses visual information about where the object is, as well as information about our current body position and self-movement. This information changes constantly and quickly, and so there is a continuous, sophisticated feedback loop where the brain converts the information into the correct and precise muscle response. A key component of this feedback is the 'stretch reflex' of muscle, which occurs milliseconds before the actual voluntary muscle movement.

"Several studies have suggested that the brain integrates multiple types of sensory information to achieve voluntary muscle control," explains lead author Sho Ito, a researcher at NTT Communication Sciences Laboratories, Kanagawa, Japan. "However, it is not known whether control of the initial stretch reflex is calculated from multiple sensory sources or from a single source, such as visual information. In this study we examined how altering visual cues, such as distorting or eliminating this information, affected the intensity of muscle stretch reflexes."

The team conducted experiments with people who were asked to move a cursor towards a visual target. In the first experiment, the movement of the cursor was changed, distorting the visual feedback participants received. The researchers calculated the effect of this change in visual cursor feedback on muscle stretch reflex by mechanically measuring muscle activity at the wrist. They found that by introducing a discrepancy between the actual hand movement and the movement of the cursor on the screen, the strength of the muscle stretch reflex was reduced.

Next, they compared muscle stretch reflex when people received normal visual feedback on how the cursor was moving versus receiving a mirror-reversed version of how the cursor moved. In half of the trials, the cursor was made to disappear entirely during the task. Both the distortion and removal of the cursor contributed to changes in the muscle stretch reflex. Removal of the cursor reduced the intensity of the stretch reflex, suggesting that being able to see the cursor is important for sufficiently activating movement correction. Moreover, the longer the participants were unable to see the cursor, the lower the intensity of the stretch reflex and the greater the overall variability in people's movements. This suggests that being certain of our limb positioning is important in regulating the stretch reflex.

In the final experiment, the researchers looked at whether processing of visual information to coordinate muscle movement is always accompanied by a reduction in the muscle stretch reflex. For this, participants had to move the cursor towards the target again, but this time the target jumped around. This allowed the team to measure reflexes in the processing of visual information as well as the muscle stretch reflexes previously calculated. They found that the decrease in intensity of the muscle stretch reflex occurred only when distortion was introduced in the visual feedback, but not by a distorted map between visual target and motor action.

"Our study suggests that in the absence of clear visual cues, participants feel unsure of their own hand position, which reduces muscle stretch reflex and prevents an inaccurate or inappropriate movement," concludes senior author Hiroaki Gomi, Senior Distinguished Researcher and Group Leader at NTT Communication Sciences Laboratories. "The results show that feedback responses that control movement are calculated by the brain not from a single signal, but from multiple sources of sensory information including our vision, posture and sense of self-movement."

A research team at the German Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) developed a method to isolate and cryopreserve testicular cells. This will allow the safekeeping and biobanking of gametes and other cells of the male reproductive tract of threatened or endangered feline species. The findings have been published in the scientific journal "Cryobiology".

Cryopreservation in liquid nitrogen at -196°C is a common procedure to store germ cells (sperm and eggs) and embryos but can be damaging to cells. Initially, the team tested two different "freezing speeds", as the extent of freezing damage strongly depends on the speed of temperature reduction during the freezing process. To ensure that germ cells and embryos are functional again after thawing, cryoprotectants are usually applied before freezing. These must penetrate the cells before the temperature is lowered in order to prevent or weaken the formation of ice crystals inside the cells and thus prevent damage. Since the most commonly used cryoprotectants are cytotoxic at higher concentrations, the scientists tested two different concentrations for freezing.

Whereas usually a cryoprotectant penetrates individual cells relatively quickly, cells inside the tissue of an organ are difficult to reach by the cryoprotectant. In this study, the testicular tissue was therefore not preserved in small pieces but - after dissolution of the tissue complex - as a cell suspension so that the cryoprotectant could penetrate individual cells faster. This method has already been successfully used in some mammalian species and was adapted by scientists at the Leibniz-IZW for the conservation of feline testicular cells. To dissolve the tissue complex as gently as possible, the Leibniz-IZW researchers combined the mechanical preparation steps with the interruption of cell to cell contacts using a cocktail of enzymes.

"A particular problem in cryopreserving tissue or cell suspensions is the assessment of cell recovery after thawing. Ultimately, cell functionality can only be achieved in long-term cell culture experiments. However, in order to optimise the freezing process in the short term, we used two methods to assess the viability of the cells," explains Mohammad Bashawat, scientist at the Leibniz-IZW. Using fluorescent reporter molecules, the lower concentration of cryoprotectant combined with a slow freezing speed was clearly the most beneficial method. About 45 % of cryopreserved testicular cells of castrated domestic cats were vital again after thawing. Comparably good results were obtained in two pilot studies with testicular cells of an Asian golden cat and a cheetah. The Leibniz-IZW research team sees this as an important step towards preserving the germ lines of valuable animals for future applications in the context of species conservation and the maintenance of diversity in their genomes.

Of the 39 cat species that are currently extant, 25 are on the "Red List" of the International Union for the Conservation of Nature (IUCN) with a status varying from "vulnerable" to "critically endangered". Measures to enhance reproduction are becoming increasingly important for the conservation of genetic diversity in these species. These measures include cryopreservation of germ cells and artificial insemination. The testes of males which died or had to be euthanised contain stem cells and numerous immature precursors of male germ cells. In future, these could hopefully be matured into spermatozoa during spermatogenesis in the "test tube", as has previously been shown by research groups working with mice and humans. In order to have testicular cells of feline species available for such future projects, their cryopreservation is the method of choice, as this allows an almost unlimited storage of this valuable gene reserve ("cryobanking"). This is especially true for individuals which cannot supply functionally "mature" sperm because of their age or state of health.

More than 60 odorous substances were identified using combined chemo-analytical methods. The information gained provides a targeted strategy for avoiding off-odors. The results of this collaborative study with the Chair of Aroma and Smell Research at the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and the University of Alicante have now been published*.

In order to meet the targets of the new EU Packaging and Packaging Waste Directive concerning the recycling of packaging waste, new markets for recyclates produced from waste plastic packaging must be found. Recyclates produced from waste plastic packaging must have no off-odors if they are to be used as secondary raw materials for the manufacture of high-quality consumer products. Indeed, the off-odors in plastic recyclates prevent a closed cycle for the recycling of plastic packaging materials. Currently, there is a particularly high reusage rate for recyclates produced from polyethylene terephthalate (PET) bottles.

LDPE packaging waste in focus

The Sensory Analytics department at the Fraunhofer IVV characterizes and optimizes plastics and recyclates. The odorants in HDPE waste and the recyclates produced from packaging from bodycare products and detergents have already been analyzed. Low density polyethylene (LDPE) is one of the most commonly used plastics. It is widely used for packaging materials such as plastic shopping bags. Via various collection systems these bags end up as packaging waste. Part of the current study on post-consumer LDPE shopping bags concerned the effect of the collection strategy on the sensory impairment of the waste.

Identification of odorants - the key step

Identification of the substances causing off-odors is essential in order to be able to take measures for odor optimization. Most of the odorants identified in the study are typical metabolites of microorganisms. Many of these metabolites had a cheese-like or feceslike odor. The odorants included carboxylic acids and sulfur-containing and nitrogencontaining components. The chemical structures of the odorants gave key insight into their origin. Using this information, the pathways into the packaging waste and via the recycling process into the recyclate were identified. Depending on which process step cannot remove an odorant or even results in a new odorant, targeted measures can be taken to reduce odorants or avoid the formation of new odorants.

Odorant reduction via separate collection in the yellow bag

The study showed that the way the packaging waste is collected has a large bearing on the odor quality of plastic shopping bags. There are significant benefits by separate collection in the yellow bag. Waste collected in this way had a significantly lower overall odor. In contrast, the waste fraction collected in the general household waste had more intense cheesy-like, sulfur-like, and feces-like odors. The higher organic fraction in the general waste favors the formation of these microbial degradation products. It was also demonstrated that the post-consumer LDPE shopping bags from the separate collection that were washed at 60 degrees had fewer odorants and a reduced overall odor than the unwashed bags.

Methods for odor identification in plastic waste

The Fraunhofer IVV scientists used sensory analytics to identify the odors. Sensory evaluation of the sample materials was first undertaken by a trained sensory panel. The odorants were then identified using chemo-analytical methods such as gas chromatography - olfactometry and with two-dimensional coupling with mass spectrometry. This enabled the chemical structures to be determined and also possible formation pathways and sources of the odorants to be identified. These key findings can now be used to develop customized solutions for optimization of the odor of plastic recyclates, starting at the waste collection stage.

Three previously unknown genetic mechanisms have been discovered in causing myopia otherwise known as short or near-sightedness, finds a new study.

The study, published today in Nature Genetics, led by King's College London, UCL and Kaiser Permanente in the USA, with the participation of the 23andMe, the genomics consumer company, found the ways in which genetics can play a part in myopia.

The study analysed the DNA in relation to the eyesight and degree of myopia in over half a million volunteers. The study identified about a thousand genetic variations in almost 450 genes which appeared to account for many cases of moderate or severe myopia in the population.

It found that the condition, which affects a third of the population in the United Kingdom, can be caused by the mechanisms by which light signals are transmitted by the retina in the eye to the brain. This study also showed other parts of the eye that transmit light are also involved. The findings of genetic markers may lead to being able to predict the condition in children.

Genes that participate in the maintenance of circadian rhythm were shown to be important in myopia and genes responsible for pigmentation of the eyes, hair and skin, were also associated.

Dr Pirro Hysi, from the School of Life Course Sciences, King's, said: "Myopia is an amazingly complex disorder, and for the first time we now have enough of the jigsaw pieces that the biology is becoming clear."

Myopia is commonly passed on from parents to children and genetics can reveal previously unknown myopia-causing mechanisms that may inspire future treatments. The study found that genes involved in the circadian rhythm - the inner biological clock regulating our 24-hour long sleep and wake cycles - could be an important factor.

Professor Jugnoo Rahi, from UCL Great Ormond Street Institute of Child Health, said: "Changes in day and night cycles are a possible explanation for the previous observations that myopia is more common in those who spend less time outdoors."

Dr Eric Jorgenson, from Kaiser Permanente North California said: "We previously knew that some severe genetic disorders affecting pigmentation caused changes at the back of the eye and resulted in severe myopia, but the strength and extent of the association between pigmentation and myopia in the general population was surprising."

If patients inherit enough genetic variants underlying these processes, short-sightedness will develop. For the first time, a genetic model based on the identified DNA variants successfully predicted up to 75% of myopia in the participants tested.

Professor Chris Hammond, from the School of Life Course Sciences, King's, said: "Very excitingly, we are now heading towards having the ability to predict which children will become short-sighted based on their genetic markers. If we can develop treatments to prevent myopia, these genetic findings may be able to help us identify those who are at highest risk and need them most."

Scientists have revealed intricate structural changes in plants, fungi and bacteria in response to light, according to a new study published today in the open-access journal eLife.

The findings provide new insights into the function of protein molecules called phytochromes that are present in these three types of organisms. The results could lead to tools that control the function of phytochromes to achieve more efficient growth patterns in plants and crops.

Plants constantly adapt to changes in light and control their growth patterns according to light availability. They achieve this through phytochromes, the origin of light detection in all vegetation on Earth. Phytochromes can adopt two different shapes depending on the light available. To achieve this change in shape, a cascade of signals occurs starting at the chromophore - the point within the phytochrome where light is absorbed.

"The phytochrome allows organisms to distinguish between two colours of light, giving plants, fungi and bacteria primitive two-colour vision," explains lead author Elin Claesson, a doctoral student at the University of Gothenburg, Sweden. "Key to its function is the initial response to light, where the light signal is translated into structural changes over a fraction of a second. The mechanisms that allow this translation are poorly understood, because the technology for studying phytochromes immediately after light reaches them has not previously been available."

To address this gap, the team led by Sebastian Westenhoff, Professor at the Department of Chemistry & Molecular Biology, University of Gothenburg, and Marius Schmidt, Professor at the Physics Department, University of Wisconsin-Milwaukee, US, used a novel X-ray laser that can capture pictures of proteins at an atomic level every 10 femtoseconds (a quadrillionth of a second). This enabled them to reveal the movement of each atomic component of the phytochrome protein and piece together the cascade of events that triggers growth in response to light.

The team found surprisingly large rearrangements of the chromophore and its surrounding protein structures immediately after light absorption. They observed the twisting of part of the chromophore called the D-ring, which in turn causes displacement of the neighbouring rings as well as changes of atoms around the chromophore. Surprisingly, they also discovered the release of a water molecule, called pyrrole water, that is found in the same place in phytochromes across all organisms.

"These findings demonstrate that the initial response to light is highly collective and that many parts of the chromophore and phytochrome protein play an important role," concludes senior author Sebastian Westenhoff. "Our study confirms a previous working model of the twisting motion of the D-ring and suggests that the pyrrole water molecule is also important in this process. We propose that both chemical events work together enabling phytochrome proteins to translate light into structural signals, guiding the growth and development of plants, fungi and bacteria on Earth."

A study of women who experienced mental ill-health from a hormonal contraception indicates they value their mental well-being higher than a satisfactory sex life. Their experiences can influence their choice of contraception. This is one of four themes that researchers have identified in interviews with 24 women who experience negative effects of some hormonal contraception. The study, from Linköping University in Sweden, has been published in the European Journal of Contraception and Reproductive Health Care.

Gynaecologist Agota Malmborg often sees women who experience negative effects on sexual desire or mental health from hormonal contraception methods, such as pill, patch and ring. Questions of sexual undesired effects have been examined previously, but it has not been established whether female sexual function is directly linked with the hormones used in contraceptives, nor how advice should be formulated for the women who experience undesired effects.

In the present study, recently published in the European Journal of Contraception and Reproductive Health Care, Agota Malmborg and her colleagues have examined in depth the significance of problems for the women and their choice of contraceptive method. The researchers carried out extensive interviews with 24 women who had described in a previous questionnaire that they experienced a reduced sexual desire when using hormonal contraception. Four themes were identified.

Women who experienced a negative effect on mood from hormonal contraception described this as an important experience that was more significant than any negative effect on their sexual desire. Women who had experienced a worsening of their mental health were reluctant to try hormonal contraception again.

Most of the women said that it took time and experience, not only of the use of hormones but also of the natural cycle of menstruation and its variation, in order for them to gain a better understanding of the body's interactions between hormones, sexual function and mental state.

Another theme that the researchers identified concerned some women who experienced that hormonal contraception affected their sexual function. These women described how their body and genital area did not respond to stimuli, such as caresses, suggestive actions by another, and thoughts. Even though the women were ready for sexual activity, their body felt inaccessible, which in turn reduced their sexual desire.

"This was a new insight for us - that sexual desire starts not only in the head or as a response to, for example, caresses. It is also necessary that conditions in the genital area are beneficial. Some women described how the genital area became more swollen and mucous secretions became more fluid when ovulation occurred, and they experienced this as positive for their sexual desire. These women felt that they lost this ability when using hormone-based contraception", says Agota Malmborg. She is gynaecologist at Kvinnokliniken Ryhov in Jönköping and defended her doctoral thesis at Linköping University in December 2019.

The study also made it clear that an advisor, who is most often a midwife, plays an important role and can make a huge difference on how women experience these effects. An advisor can hasten the process of a woman coming to insight into which method of contraception is most suitable, and can make her choice of method easier. In contrast, less satisfactory advisory sessions can delay insight.

"It is extremely important to follow up whether a woman is satisfied with the method chosen. This is particularly important for young women, who are at the start of their sexual life, and have not yet gained experience of how their own hormones, sexual desire and mental health can vary", says Agota Malmborg.

She believes that further research in the field should focus on women who experience negative effects of hormonal contraception. Is it, for example, possible to predict which women run an increased risk of being affected?

"We must continue to work on which recommendations for contraception the healthcare system should give to the relatively small subgroup of women who experience undesired effects from hormonal contraception. This should also be a signal to researchers to continue to develop new methods of contraception, both with and without hormones, such that a wider range becomes available. Thus, we hope that more women, and indeed more men, can find a method that is suitable for them", says Agota Malmborg.

Organic soybean producers using no-till and reduced-tillage production methods that incorporate cover crops -- strategies that protect soil health and water quality -- can achieve similar yields at competitive costs compared to tillage-based production.

That's the conclusion of a new study by researchers in Penn State's College of Agricultural Sciences. These findings are significant, according to lead researcher John Wallace, assistant professor of weed science, because they may contribute to increased sustainable domestic production of organic soybeans.

The experiment, which focused on finding ways to reduce the intensity or frequency of tillage or soil disturbance in organic field crop production systems, was conducted on certified organic land at Penn State's Russell E. Larson Agricultural Research Center. Researchers compared tillage-based soybean production preceded by a cover crop mixture interseeded into corn, with reduced-tillage soybean production preceded by a roller-crimped cereal rye cover crop that was sown after corn silage.

According to researchers, the reduced-tillage soybean sequence resulted in 50% less soil disturbance compared to the tillage-based soybean sequence across study years, promising substantial gains in water quality and soil conservation. In addition, budget comparisons showed that the reduced-tillage soybean sequence resulted in lower input costs than the tillage-based soybean sequence. However, the reduced-tillage system was about $46 per acre less profitable because of slightly lower average yields.

"Organic grain producers are interested in reducing tillage to conserve soil and decrease labor and fuel costs," Wallace said. "In our research, we examined agronomic and economic tradeoffs associated with alternative strategies for reducing tillage frequency and intensity in a cover crop-soybean sequence, within a corn-soybean-spelt organic cropping system."

Weeds are a serious problem for organic growers of field crops because growers are unable to kill them with herbicides. Significantly, researchers found that weed biomass did not differ between soybean-production strategies. That matters because tillage and cultivation are the primary methods used by organic producers to reduce weeds and other pests.

Tillage-based soybean production marginally increased grain yield by fewer than three bushels per acre compared with the reduced-tillage soybean system.

The study, recently published in Renewable Agriculture and Food Systems, is the latest in a 15-year-long line of organic no-till research conducted in the College of Agricultural Sciences and led by William Curran, professor emeritus of weed science. Although he retired last year, Curran also participated in this study. Organic no-till field crop research continues at Penn State under the direction of Wallace and entomologist Mary Barbercheck.

Finding ways to allow more domestic production of organic soybeans is a huge issue, Wallace contends, because more than 70% of the organic soybeans that feed organically produced poultry in the U.S. are imported. They primarily come from Turkey, India and Argentina.

"There have been many cases of fraudulent imports -- crops that were not really produced organically -- coming from some of those countries, and that's depressed the premiums that U.S. producers are getting because we're being flooded with these imports," Wallace said. "And they're driving down the prices that U.S. producers can get."

Wallace added that he'd like to help American organic growers, especially those in the Mid-Atlantic region, produce more soybeans using environmentally responsible no-till and reduced-tillage methods.

Amyloid plaque formation directly causes brain tissue loss in animals, but a drug called lithium reduces the life-shortening effects of this loss, shows a study published today in eLife.

Patients with Alzheimer's disease experience progressive memory loss and loss of brain matter over time. This study provides new details about what happens in the brain in Alzheimer's disease and suggests a potential strategy to slow it.

Both the production of small protein fragments called Amyloid-ß and the assembly of these fragments into large clusters or plaques have been implicated in Alzheimer's disease. But teasing apart the role of Amyloid-ß versus the role of plaque formation has been difficult.

"There is currently a lack of tools that can directly control the formation of Amyloid-ß plaques in animals, which would allow scientists to examine the effects of plaque formation in Alzheimer's disease," explains lead author Lim Chu Hsien, a researcher at, and recent graduate of Yale-NUS College, Singapore, who is currently pursuing her medical degree at Duke-NUS Medical School, Singapore.

Using a technique called optogenetics, Lim and her colleagues were able to engineer Amyloid-ß fragments that would form plaques when exposed to light in the brains of fruit flies, tiny worms and zebrafish. The experiments showed that both the presence of Amyloid-ß and the formation of plaques were detrimental to the lifespan and health of these animals.

The team found that formation of the plaques caused both metabolic problems in the brain and physical damage that led to a loss of brain tissue. It also impaired the animals' sensory motor skills and behaviour.

Next, the researchers tested whether a drug called lithium that is used to treat some psychiatric disorders might mitigate the harm caused by light-induced plaque formation in fruit flies. They added lithium to the flies' food and found that this led to an extended lifespan in the insects.

"These data demonstrate the potential use of our optogenetics system for Alzheimer's disease drug testing," explains senior author Nicholas Tolwinski, Associate Professor of Science (Life Sciences) at Yale-NUS College, Singapore. "This light-driven plaque formation approach could be used in cells to enable mass screening of potential treatments. It might also help scientists study the effects of treatments on the different stages of Alzheimer's disease development."

WASHINGTON--Individuals taking a class of steroid hormones called glucocorticoids for conditions such as asthma, allergies and arthritis on a routine basis may be unable to mount a normal stress response and are at high risk if they are infected with the virus causing COVID-19, according to a new editorial published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Glucocorticoids are a class of medications used to treat a variety of inflammatory conditions and administered by many different routes, including tablets, topical creams and inhaled medications. Patients taking these medications may be more susceptible to COVID-19 as a result of the medication suppressing the immune system. They may also experience more severe disease once infected because these medications suppress their own steroid response to infection. Injectable supplemental glucocorticoid therapy in this setting can reverse the risk of potentially fatal adrenal failure and should be considered in every case.

Individuals with known primary adrenal insufficiency, also known as Addison's disease, and secondary adrenal insufficiency occurring in hypopituitarism should also take extra precautions. If patients develop symptoms such as a dry continuous cough and fever, they should double their oral glucocorticoid dose immediately and continue doing so until the fever has subsided. They, too, will require injectable glucocorticoid therapy should their condition worsen.

Endocrinologists can play a key role in recognizing, managing and implementing these measures, according to the authors.

According to the World Health Organizations, there are more than 719,000 confirmed cases of COVID-19. More than 33,000 people have died from the disease as of March 31.

"In our professional lives, we have not witnessed a healthcare crisis of this magnitude and severity," the authors wrote.

Among individuals with diabetes who contract COVID-19, the severity of the illness appears to be worse than in individuals who do not have diabetes, according to the authors. Published research from the Wuhan province in China found those with diabetes and high blood pressure were overrepresented among severely ill patients and those who died.

Scientists have already helped to uncover how the virus responsible for COVID-19 enters cells and spreads from one individual to another. Some have already made preliminary observations regarding the virus' interactions with the endocrine system.

"Endocrine-related targets are at the forefront of discovery science as we collectively tackle this pandemic," the authors wrote.

Philadelphia, March 31, 2020 - Genetic studies of attention-deficit/hyperactivity disorder (ADHD) show that it takes many common genetic variations combining together in one individual to increase risk substantially. At the same time, neuroimaging experts have found differences in how the brains of people diagnosed with ADHD are functionally connected. However it's unclear how genetic risk might be directly related to altered brain circuitry in individuals diagnosed with ADHD.

A new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, combined genetics and functional brain imaging to find that both genetic and neural factors influence ADHD diagnosis.

In the study, researchers focused their imaging analyses on selected brain regions, looking specifically at the communication between those regions and the rest of the brain in children with the diagnosis. One region's connectivity was linked to a higher risk of ADHD, while a second, different part of the brain seemed to compensate for genetic effects and reduced the chances of an ADHD diagnosis.

The authors believe this research will lead to a better understanding of how genetic risk factors alter different parts of the brain to change behaviors and why some people at higher genetic risk do not exhibit ADHD symptoms.

"We are now in a phase with enough data to answer some questions about the underlying genetics of a disorder that in the past have been difficult to elucidate," said senior author Damien Fair, PhD. "Previous imaging studies had shown different functional connectivity, and we assume those have a genetic basis."

ADHD is a neurodevelopmental psychiatric disorder that affects about 5 percent of children and adolescents and 2.5 percent of adults worldwide. The disorder is characterized by inattentive or hyperactive symptoms with many variations.The paper focuses on 315 children between the ages of 8 and 12 who participated in a longitudinal ADHD study that began in 2008 at the Oregon Health & Science University in Portland, WA, USA, as a collaboration between Dr. Fair, a neuroscientist and imaging researcher, and co-author Joel Nigg, PhD, a pediatric psychologist.

In this study, led by Robert Hermosillo, PhD, a postdoctoral researcher in Fair's lab, the team selected three areas of the brain based on a brain tissue database that showed where ADHD risk genes were likely to alter brain activity. To measure the brain communication to-and-from these regions on each side of the brain, the researchers used resting-state non-invasive magnetic resonance imaging (MRI) scans.

To begin to bridge genetic and neuroimaging studies of ADHD, researchers used MRI to scan the brains of children. Two regions previously associated with ADHD stood out. In one, a higher ADHD genetic risk correlated with a more active brain circuit anchored by the nucleus accumbens (orange arrow). Interestingly a weaker connection anchored by the caudate nucleus (blue arrow) seemed to protect children at high genetic risk from ADHD behaviors.

Next, they calculated a cumulative ADHD genetic risk score in the children, based on recent genome-wide studies, including a dozen higher-risk genetic regions reported two years ago by a large international collaboration called the Psychiatric Genetics Consortium.

In one brain region anchored by the nucleus accumbens, they found a direct correlation with genetics. "Increased genetic risk means stronger communication between the visual areas and the reward centers," explained Dr. Hermosillo.

Another brain region anchored by the caudate yielded more puzzling results until the researchers tested its role as a mediator between genetics and behavior. "The less these two regions talk to each other, the higher the genetic risk for ADHD," said Dr. Hermosillo. "It seems to provide a certain resiliency against the genetic effects of ADHD. Even among those with high risk for ADHD, if these two brain regions are communicating very little, a child is unlikely to end up with that diagnosis."

A third region, the amygdala, showed no correlation between connectivity to the other brain regions and the genetics.

According to the authors, the findings suggest that a genetic score alone will not be enough to predict ADHD risk in individuals because the results show both a genetic and neural contribution toward an ADHD diagnosis. A future diagnostic tool will likely need to combine genetics and brain functional measures. "The brain is not at the mercy of genes," added Dr. Hermosillo. "It's a dynamic system not preprogrammed for disorders. It has the capacity to change."

According to a popular view, creativity is a product of the brain’s right hemisphere – innovative people are considered “right-brain thinkers” while “left-brain thinkers” are thought to be analytical and logical. Neuroscientists who are skeptical of this idea have argued that there is not enough evidence to support this idea and an ability as complex as human creativity must draw on vast swaths of both hemispheres. A new brain-imaging study out of Drexel University’s Creativity Research Lab sheds light on this controversy by studying the brain activity of jazz guitarists during improvisation.

The study, which was recently published in the journal NeuroImage, showed that creativity is, in fact, driven primarily by the right hemisphere in musicians who are comparatively inexperienced at improvisation. However, musicians who are highly experienced at improvisation rely primarily on their left hemisphere. This suggests that creativity is a “right-brain ability” when a person deals with an unfamiliar situation but that creativity draws on well-learned, left-hemisphere routines when a person is experienced at the task.

By taking into consideration how brain activity changes with experience, this research may contribute to the development of new methods for training people to be creative in their field. For instance, when a person is an expert, his or her performing is produced primarily by relatively unconscious, automatic processes that are difficult for a person to consciously alter, but easy to disrupt in the attempt, as when self-consciousness causes a person to “choke” or falter.

In contrast, novices’ performances tend to be under deliberate, conscious control. Thus, they are better able to make adjustments according to instructions given by a teacher or coach. Recordings of brain activity could reveal the point at which a performer is ready to release some conscious control and rely on unconscious, well-learned routines. Releasing conscious control prematurely may cause the performer to lock-in bad habits or nonoptimal technique.

The study was led by David Rosen, PhD, a recent Drexel doctoral graduate and current co-founder and chief operations officer of Secret Chord Laboratories, a music-technology startup company; and John Kounios, PhD, professor of psychology and director of the doctoral program in applied and cognitive brain sciences in Drexel’s College of Arts and Sciences.

The team recorded high-density electroencephalograms (EEGs) from 32 jazz guitar players, some of whom were highly experienced and others less experienced. Each musician improvised to six jazz lead sheets (songs) with programmed drums, bass and piano accompaniment. The 192 recorded jazz improvisations (six jazz songs by 32 participants) were subsequently played for four expert jazz musicians and teachers individually so they could rate each for creativity and other qualities.

The researchers compared the EEGs recorded during highly rated performances with EEGs recorded during performances that were rated to be less creative. For highly rated performances compared with less-creative performances, there was greater activity in posterior left-hemisphere areas of the brain; for performances with lower ratings compared with those with higher ratings, there was greater activity in right-hemisphere, mostly frontal, areas.

By themselves, these results might suggest that highly creative performances are associated with posterior left-hemisphere areas and that less-creative performances are associated with right-hemisphere areas. This pattern is misleading, however, according to the researchers, because it does not take experience of the musician into consideration.

Some of these musicians were highly experienced, having given many public performances over decades. Other musicians were much less experienced, having given only a very small number of public performances. When the researchers reanalyzed the EEGs to statistically control for the level of experience of the performers, a very different pattern of results emerged. Virtually all of the brain-activity differences between highly creative and less-creative performances were found in the right hemisphere, mostly in the frontal region.

This finding is in line with the team’s other research that used electrical stimulation to study how creative expression is generated in musicians’ brains and its study of how experienced and inexperienced jazz musicians reacted to being exhorted to play “even more creatively.”

The new study reveals the brain areas that support creative musical improvisation for highly experienced musicians and their less-experienced counterparts and addresses the controversial question of the roles of the left and right hemispheres in creativity. Furthermore, it raises an important issue that goes to the heart of the definition and understanding of creativity.

“If creativity is defined in terms of the quality of a product, such as a song, invention, poem or painting, then the left hemisphere plays a key role,” said Kounios. “However, if creativity is understood as a person’s ability to deal with novel, unfamiliar situations, as is the case for novice improvisers, then the right hemisphere plays the leading role.”

The study, “Dual-Process Contributions to Creativity in Jazz Improvisations: An SPM-EEG Study” was funded by a grant from the National Science Foundation. It was published in the journal NeuroImage. Co-authors included Yongtaek Oh, doctoral student; Brian Erickson, post-doctoral researcher; Fengqing (Zoe) Zhang, PhD; and Youngmoo Kim, PhD, of Drexel.

DOI

10.1016/j.neuroimage.2020.116632

Fast communication between our brain cells - or neurotransmission as it is called - is hugely important for our brain to work properly. Some of the messengers involved in this form of communication are neuropeptides, which are chemicals produced in the brain.

Some of these peptides are involved in causing the feeling of pain. In a new study, researchers from the University of Copenhagen show how the neuropeptide Big Dynorphin binds to a receptor involved in sending pain signals around the brain.

"We have mapped exactly how and where Big Dynorphin binds to this receptor, which can cause a pain signal to be sent inside the body. Big Dynorphin is the most potent regulator of this particular receptor discovered in the human body so far. The painkillers that we use today affect other types of receptors. This means that our discovery could pave the way for a new type of painkilling medicine via this receptor, potentially helping to circumvent some of the typical adverse effects of opioids." says author to the study Stephan Pless, Professor at the Department of Drug Design and Pharmacology.

Relevant for inflammation and chronic pain

The new study is published in PNAS and it investigates the interaction between Big Dynorphin and the receptor called Acid-Sensing Ion Channel (ASIC). The researchers have mapped the interaction and signaling using a wide range of methods.

They made manipulations on the peptide and the receptor using technologies such as electrophysiology, genetically encoded cross-linkers, as well as CRISPR. Normally, the biological interaction within the brain cell occurs very fast, but their approach allowed the researchers to trap the interactions and map them.

"We know that both the receptor and Big Dynorphin are upregulated in patients with inflammation and chronic pain. This means that there are many more of them than under normal conditions. And that, in theory at least, can lead to more pain and the risk of long-lasting negative effect on brain health. This means that our result could have implications for these diseases in terms of drug development," says co-first author of the study Dr Nina Braun.

Potential for pain reduction

Other researchers have previously shown that if they knock out the ASIC receptor, they have been able to reduce pain in mouse models. This underlines the potential of the new findings from the University of Copenhagen.

The researchers are looking forward to exploiting the mechanism pharmacologically in their coming studies. They hope to find relevant compounds that could show potential for pain reduction for these vulnerable patient-groups.