Culture

Researchers at the University of Maryland School of Medicine published one of the most comprehensive analyses of how genes get expressed during infection (known as a transcriptome). The analyses include three different strains of the bacteria Streptococcus pneumoniae, which causes pneumonia, meningitis and middle-ear infections. It also includes analyses of the lungs and four other organs in an animal model where the bacteria resides, multiplies and takes hold in the body. Their findings were published today in the Proceedings of the National Academy of Sciences.

"Our new analysis provides valuable new information about the animal host and pathogen interactions that take place during pneumococcal infections," said study principal investigator Hervé Tettelin, PhD, a Professor of Microbiology and Immunology, and scientist at the Institute for Genome Sciences in the University of Maryland School of Medicine. "It could ultimately help researchers develop new treatments for this bacterial infection."

Symptoms of pneumococcal infection can include fever, cough, shortness of breath, chest pain, stiff neck, confusion, increased sensitivity to light, joint pain, chills, ear pain, sleeplessness, and irritability, according to the Centers for Disease Control and Prevention. With the introduction of the first pneumococcal vaccine in 2000, deaths attributable to these infections have declined. However, increasing antibiotic resistance have made some of these infections more difficult to treat.

The University of Maryland School of Medicine researchers collaborated with researchers at the University of Alabama at Birmingham and Yale University School of Medicine to analyze gene expression in various infection sites including the nose and throat passages, the heart, bloodstream, lungs, and kidneys. They created an atlas from this gene expression data and found that the bacteria behaves differently depending on which site it infects within the mouse model, and the mouse organs, in turn, also respond differently. They also found certain S. pneumoniae genes were always highly expressed at all anatomical sites, which makes them ideal targets for new vaccines or therapies. In an animal challenge experiment, the researchers found that an anti-inflammatory treatment called interferon beta worked to prevent the bacteria from invading vital organs.

"This promoted host survival and provided us with important insights into potentially new avenues for treatment," said study co-author Adonis D'Mello, a graduate student in molecular medicine at the Institute for Genome Sciences. "We were able to build upon analytical pipelines to provide a more comprehensive way of studying diverse systemic pathogens."

Funding was provided through the Merck Investigator Studies Program that supports hypothesis-generating clinical and pre-clinical research that is initiated, designed and implemented by external investigators. This project was also supported with funds from the National Institutes of Health, National Institute of Allergy and Infectious Diseases.

"This is a very exciting basic research finding that could have widespread implications in our understanding of a widespread and potentially dangerous infectious disease," said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "It also has broader applicability for the field of transcriptome research to identify potential new treatments for diseases."

Unraveling the links among obesity, aging, telomere lengths and metabolic diseases is the subject of the study published today in Nature Metabolism by a collaborative research team at The University of Texas Health Science Center at Houston (UTHealth).

Telomeres act as protective caps at the end of chromosomes to prevent them from replication errors during cell divisions. Every time a chromosome replicates itself, telomeres shorten. When the telomeres become too short, the cell can no longer replicate its chromosomes safely and becomes arrested, or senescent. That shortening has been linked to the aging process and development of degenerative diseases.

"Recent studies have also shown the connection between obesity-induced metabolic diseases, such as Type 2 diabetes, and the accumulation of senescent cells, which entered the state of irreversible proliferation arrest," said lead author Mikhail Kolonin, PhD, professor and Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research with McGovern Medical School at UTHealth. "Cell senescence can be caused by telomere shortening due to excessive stem cell division."

It has been unclear how excessive feeding and obesity are linked with cell senescence mechanistically. The authors hypothesized that overfeeding, causing excessive stem cell proliferation and telomere attrition, predisposes adipose (fat) cells to premature senescence and tissue dysfunction.

"Until now we have not been able to investigate the process in laboratory mice because they have abnormally long telomeres that do not shorten sufficiently to trigger replicative senescence within their lifespan," said Kolonin, who is the director of the Center for Metabolic and Degenerative Diseases at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at McGovern Medical School.

Telomere shortening is prevented by telomerase, an enzyme rebuilding the telomeres at each cell division. The group created mice with telomerase genetically inactivated in stem cells giving rise to adipocytes, the lipid-storing cells of fat tissue. Simulating clinical observations, these mice underwent replicative senescence in fat tissue, further advanced by high-calorie diet, and developed Type 2 diabetes.

To further assess translational relevance of these findings, the group analyzed biopsies from patients undergoing bariatric surgery. Shorter telomeres were observed in patients who were more resistant to the weight loss effects of the treatment and had a history of metabolic dysfunction. Combined, these results provide a new insight on the mechanistic links between aging, diet-induced obesity, and metabolic disease.

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Accounting for recent population aging is critical for estimating non-COVID-19 excess deaths in the U.S.

Estimates of excess mortality during the coronavirus disease 2019 (COVID-19) pandemic provide an important metric for quantifying deaths due to COVID-19 as well as those indirectly caused by COVID-
19. To evaluate the excess deaths in 2020 without consideration of changes to the underlying population structure can result in overestimated excess deaths. The growth of the U.S. population, particularly in older age groups, means a higher expected number of deaths in 2020 from all causes, even in the absence of COVID-19.

Researchers from the National Cancer Institute used data from the CDC National Center for Health Statistics and the U.S. Census Bureau to estimate excess mortality in the period March through August 2020. By accounting for the recent aging of the population, they found the number of excess non-COVID-19 deaths was 44,600, which is 65 percent fewer than estimated without considering population aging. The number of COVID-19 deaths during this period did not change with adjustment for population structure. According to the study authors, these excess death estimates may help guide clinical and public health interventions to prevent future unnecessary deaths by highlighting excess deaths by cause and age. They note that the tremendous loss of life directly or indirectly due to COVID-19 over such a short period should not be understated. Deaths are currently increasing with more than 17,000 COVID-19 deaths in the U.S. last week. Continued efforts to reduce COVID-19 infections and deaths remain an urgent priority.

Read the full text:https://www.acpjournals.org/doi/10.7326/M20-7385.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead corresponding, Meredith S. Shiels, PhD, MHS, can be reached through the NCI Press Office at ncipressofficers@mail.nih.gov.

2. During pandemic, researchers may need guidance on informed consent exceptions

A foundational requirement of ethical research is that persons provide informed consent. Yet, informed consent exceptions can be made when research poses no more than minimal risk to participants or would be impracticable to do without a waiver or alteration. The coronavirus disease 2019 (COVID-19) pandemic creates a challenge for these exceptions.

The authors from the University of Pennsylvania Perelman School of Medicine cite the example of a smoking-cessation trial. Before the pandemic, their institutional review board (IRB) had approved a trial comparing smoking cessation interventions among older, underserved adults. The study was approved using opt-out consent, a type of consent alteration. But because participants are required to submit samples in person or via a mobile laboratory, the risks associated with submitting samples may be higher than before the pandemic. To determine whether opt-out consent remains appropriate, the IRB must determine whether the study remains minimal risk. Examples such as this one make it important for IRBs to revisit informed consent exemptions during the pandemic.

Read the full text: https://www.acpjournals.org/doi/10.7326/M20-6993.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead corresponding, Emily A. Largent, JD, PhD, RN, can be reached through Melissa Moody at Melissa.Moody@Pennmedicine.upenn.edu.

Over 50 per cent of Asians living in the UK are severely deficient in vitamin D, leaving them more vulnerable to respiratory infections such as COVID-19 and musculoskeletal disorders, according to a large-scale population study published this week.

The journal Clinical Nutrition also reports that more than a third of Black Africans living in Britain have high levels of vitamin D deficiency, and lower socio-economic groups are more at risk.

Led by the Australian Centre for Precision Health, University of South Australia, using data from 440,581 UK Biobank participants, the study strengthens calls for a mandatory vitamin D fortification program in the United Kingdom.

Unlike most other high latitude western countries, the UK does not fortify any staple food items with vitamin D, aside from a small amount added to margarine.

The hormone is naturally synthesised in the body through sun exposure, but long winter months and less time spent outdoors have contributed to alarmingly high vitamin D deficiency in pockets of the UK, with overall levels falling below the most conservative global recommendations.

First author, UniSA PhD student Joshua Sutherland, says the findings show that certain ethnic and socio-economic groups, as well as those living in the northern areas of the UK, are far more likely to be vitamin D deficient.

"The reason that people with darker skin are more at risk is because higher levels of melanin, which increases skin pigmentation, can lessen the skin's ability to make vitamin D," Sutherland says. "But this, combined with spending more time indoors and consuming lower vitamin D-containing foods, can foster severe deficiency."

"Of almost half a million people surveyed, we found that 57 per cent of Asians were severely deficient in vitamin D (levels below 25 nmol/L) in winter/spring and 50.8 per cent in summer and autumn.

"Black Africans were the next most vulnerable (38.5 per cent deficient in winter and 30.8 per cent in summer), followed by mixed race people and Chinese participants. White Europeans had the lowest prevalence of vitamin D deficiency but many are still affected."

Vitamin D is a hormone that controls calcium levels in the blood and helps build strong bones, regulates immune and muscle function and contributes to overall health.

Regular consumption of oily fish has a protective effect, but Asians are less likely to eat fish or use vitamin D supplements compared to other ethnicities, the researchers found.

There was a clear seasonal contrast in vitamin D levels among white Europeans, with 17.5 per cent showing a deficiency in winter, compared to 5.9 per cent in summer. The seasonal variations were not as marked in other cultural groups.

Time spent outdoors, and high levels of TV and computer use were all strongly associated with a greater chance of vitamin D deficiency in white Europeans, but this association was much weaker for other ethnicities.

Nearly one third of study participants living in Edinburgh and Glasgow recorded low vitamin D levels in winter, while southern UK residents, from comparatively higher socio-economic regions, had less winter deficiency and were also more likely to take vitamin D supplements and eat more oily fish.

"These findings highlight the continuing need for effective health interventions to reduce the prevalence of vitamin D deficiency in the UK, both at the population level and within at-risk groups," Sutherland says.

"Fortification of a single food item, such as the proposed wheat fortification program, is tricky because some South Asian groups are more likely to eat millet and rice than wheat. It's clear the UK requires targeted public health measures to mitigate deficiency risk in all affected populations," he says.

The study was led by Professor Elina Hypponen, who is one of the world leading experts on vitamin D.

"The rate of severe deficiency was much higher in most population groups than we would have expected, so these results are really very alarming," says Prof Hypponen.

"The severity of vitamin D deficiency is concerning, especially with the high rates of COVID-19 infections in Europe and elsewhere in the northern hemisphere this winter. Clinical trials have shown that vitamin D supplements are beneficial in the prevention of respiratory infections and even mortality.

"Vitamin D is not expensive and the doses which have shown the greatest benefits are those that we can all acquire over the counter from the local pharmacy. Given the COVID-19 pandemic, now is really the time for all who may be affected to take action," Prof Hypponen says.

A team of astronomers used the Keck I telescope to measure the distance to an ancient galaxy. They deduced the target galaxy GN-z11 is not only the oldest galaxy but also the most distant. It's so distant it defines the very boundary of the observable universe itself. The team hopes this study can shed light on a period of cosmological history when the universe was only a few hundred million years old.

We've all asked ourselves the big questions at times: "How big is the universe?" or "How and when did galaxies form?" Astronomers take these questions very seriously, and use fantastic tools that push the boundaries of technology to try and answer them. Professor Nobunari Kashikawa from the Department of Astronomy at the University of Tokyo is driven by his curiosity about galaxies. In particular, he sought the most distant one we can observe in order to find out how and when it came to be.

"From previous studies, the galaxy GN-z11 seems to be the farthest detectable galaxy from us, at 13.4 billion light years, or 134 nonillion kilometers (that's 134 followed by 30 zeros)," said Kashikawa. "But measuring and verifying such a distance is not an easy task."

Kashikawa and his team measured what's known as the redshift of GN-z11; this refers to the way light stretches out, becomes redder, the farther it travels. Certain chemical signatures, called emission lines, imprint distinct patterns in the light from distant objects. By measuring how stretched these telltale signatures are, astronomers can deduce how far the light must have traveled, thus giving away the distance from the target galaxy.

"We looked at ultraviolet light specifically, as that is the area of the electromagnetic spectrum we expected to find the redshifted chemical signatures," said Kashikawa. "The Hubble Space Telescope detected the signature multiple times in the spectrum of GN-z11. However, even the Hubble cannot resolve ultraviolet emission lines to the degree we needed. So we turned to a more up-to-date ground-based spectrograph, an instrument to measure emission lines, called MOSFIRE, which is mounted to the Keck I telescope in Hawaii."

The MOSFIRE captured the emission lines from GN-z11 in detail, which allowed the team to make a much better estimation on its distance than was possible from previous data. When working with distances at these scales, it is not sensible to use our familiar units of kilometers or even multiples of them; instead, astronomers use a value known as the redshift number denoted by z. Kashikawa and his team improved the accuracy of the galaxy's z value by a factor of 100. If subsequent observations can confirm this, then the astronomers can confidently say GN-z11 is the farthest galaxy ever detected in the universe.

An AI developed by Japanese researchers might soon help stroke survivors get the right treatment by detecting a patient's post-stroke depression (PSD) type, a frequently seen but often overlooked neuropsychiatric manifestation after a stroke that could impair functional recovery.

The AI was developed by Hiroshima University (HU) researchers using a probabilistic artificial neural network called log-linearized Gaussian mixture network. The neural network was trained to distinguish between depression, apathy, or anxiety based on 36 evaluation indices obtained from functional, physical, and cognitive tests on 274 patients.

Details about their research that analyzed the relationship between PSD and activities of daily living independence, degree of paralysis, stress awareness, and higher brain function using machine learning are published in Scientific Reports.

Early PSD detection

The researchers said each PSD type might have different underlying neuroanatomic mechanisms which could have a distinct impact on a patient's functional recovery. And its early detection is crucial to give the appropriate treatment needed by the patient.

"Depression is a highly comorbid neuropsychiatric symptom during the acute and subacute phase after a stroke and has been reported to negatively influence functional and cognitive recovery. Thus, early diagnosis and intervention are crucial for post-stroke depression," study author Seiji Hama, a research associate at HU's Graduate School of Biomedical and Health Science, said.

"However, PSD is multifactorial, and associated neurological symptoms may hinder the detection process. This study is the first step in aiming to accurately diagnose PSD using data obtained in routine practice without any special equipment."

The researchers tested the AI's diagnostic accuracy through the receiver operating characteristic curve which visually evaluates the performance of a machine learning algorithm by giving it an area under the curve (AUC) score. An AUC score of 1.0 means a perfect performance. The PSD detection AI scored above 0.85.

Stress threshold hypothesis

Various post-stroke physical disorders, cognitive dysfunction, and mood disorders associated with stress responses are intricately intertwined, making it difficult to understand the cause of PSD and, therefore, making its diagnosis challenging.

It is uncertain whether PSD occurs as part of the mourning process due to the physical impairments after a stroke or if it is brought about by biological factors associated with brain damage.

The study results, however, suggested that reduced stress adaptability due to stroke-induced brain lesions is behind PSD.

"One of the traditional hypotheses on the PSD mechanism was 'threshold hypothesis,' consistent with many previous reports demonstrating the association between the accumulation of lacunar infarcts within the basal ganglia, thalamus, and deep white matter and PSD," they said in their study.

Hama said they intend to conduct detailed analysis using MRI images to further clarify the origins of PSD and improve techniques to diagnose it in hopes of applying the technology to wearable devices. The researchers expect patient rehabilitation would be improved through the early diagnosis and treatment of PSD.

"If this diagnostic technique of PSD becomes possible to test with a wearable device, it will be possible to use it in the local community. By combining it with the test for cognitive function, we would like to verify its application to the preventive effect of strokes," he said.

Thinking like Earthlings may have caused scientists to overlook the electrochemical effects of Martian dust storms.

On Earth, dust particles are viewed mainly in terms of their physical effects, like erosion. But, in exotic locales from Mars to Venus to Jupiter's icy moon Europa, electrical effects can affect the chemical composition of a planetary body's surface and atmosphere in a relatively short time, according to new research from Washington University in St. Louis.

"This direction of scientific investigation has been largely overlooked in the past," said Alian Wang, research professor in the Department of Earth and Planetary Sciences in Arts & Sciences. "Researchers are used to thinking 'inside the box' based on terrestrial experience."

Wang's study in the Journal of Geophysical Research: Planetsfocuses on amorphous sulfur and chlorine salts found by the Curiosity rover at Gale crater on Mars. The chemical signature of these materials could have been induced by electrochemical processes during Martian dust activities in a relatively short geologic time frame: years to hundreds of years.

Low-strength electrostatic discharge causes electrochemical reactions that transform materials on the Martian surface, Wang explained, causing loss of crystallinity, removal of structural water and oxidation of certain elements like sulfur, chlorine and iron.

"The collective chemical effect of electrostatic discharge can be significant," Wang said. "This is the core idea of our new study."

The findings could inform science priorities for the next phase of Mars exploration missions, including NASA's Perseverance rover, China National Space Administration's Tianwen-1 lander and rover, and the European Space Agency's ExoMars lander and rover.

"'Explore the subsurface' is the suggestion that we would give to the next phase of Mars exploration missions," said Bradley Jolliff, the Scott Rudolph Professor of Earth and Planetary Sciences and a co-author on the paper.

"These missions are all seeking evidence for geological and hydrological evolution at their selected landing sites, and they are especially looking for and hoping to collect samples that contain traces of past biological activity," Jolliff said. "Exploring the subsurface would enable sampling of ancient materials -- some of which might still be safekeeping precious biomarkers."

A pioneering reconstruction of the brain belonging to one of the earliest dinosaurs to roam the Earth has shed new light on its possible diet and ability to move fast.

Research, led by the University of Bristol, used advanced imaging and 3-D modelling techniques to digitally rebuild the brain of Thecodontosaurus, better known as the Bristol dinosaur due to its origins in the UK city. The palaeontologists found Thecodontosaurus may have eaten meat, unlike its giant long-necked later relatives including Diplodocus and Brontosaurus, which only fed on plants.

Antonio Ballell, lead author of the study published today in Zoological Journal of the Linnean Society, said: "Our analysis of Thecodontosaurus' brain uncovered many fascinating features, some of which were quite surprising. Whereas its later relatives moved around ponderously on all fours, our findings suggest this species may have walked on two legs and been occasionally carnivorous."

Thecodontosaurus lived in the late Triassic age some 205 million years ago and was the size of a large dog. Although its fossils were discovered in the 1800s, many of which are carefully preserved at the University of Bristol, scientists have only very recently been able to deploy imaging software to extract new information without destroying them. 3-D models were generated from CT scans by digitally extracting the bone from the rock, identifying anatomical details about its brain and inner ear previously unseen in the fossil.

"Even though the actual brain is long gone, the software allows us to recreate brain and inner ear shape via the dimensions of the cavities left behind. The braincase of Thecodontosaurus is beautifully preserved so we compared it to other dinosaurs, identifying common features and some that are specific to Thecodontosaurus," Antonio said. "Its brain cast even showed the detail of the floccular lobes, located at the back of the brain, which are important for balance. Their large size indicate it was bipedal. This structure is also associated with the control of balance and eye and neck movements, suggesting Thecodontosaurus was relatively agile and could keep a stable gaze while moving fast."

Although Thecodontosaurus is known for being relatively small and agile, its diet has been debated.

Antonio, a PhD student at the University of Bristol's School of Earth Sciences, said: "Our analysis showed parts of the brain associated with keeping the head stable and eyes and gaze steady during movement were well-developed. This could also mean Thecodontosaurus could occasionally catch prey, although its tooth morphology suggests plants were the main component of its diet. It's possible it adopted omnivorous habits."

The researchers were also able to reconstruct the inner ears, allowing them estimate how well it could hear compared to other dinosaurs. Its hearing frequency was relatively high, pointing towards some sort of social complexity - an ability to recognise varied squeaks and honks from different animals.

Professor Mike Benton, study co-author, said: "It's great to see how new technologies are allowing us to find out even more about how this little dinosaur lived more than 200 million years ago.

"We began working on Thecodontosaurus in 1990, and it is the emblem of the Bristol Dinosaur Project, an educational outreach scheme where students go to speak about science in local schools. We're very fortunate to have so many well-preserved fossils of such an important dinosaur here in Bristol. This has helped us understand many aspects of the biology of Thecodontosaurus, but there are still many questions about this species yet to be explored."

Neuroscientists at UCL have found no significant association between COVID-19 and the potentially paralysing and sometimes fatal neurological condition Guillain-Barré syndrome.

Researchers say the findings, published in the journal Brain*, along with a linked scientific commentary** by UCL and other international experts, should provide the public with reassurance, as the UK's national coronavirus vaccination programme is rolled out.

Guillain-Barré syndrome (GBS) is a rare but serious autoimmune condition that attacks the peripheral nervous system, typically affecting the feet, hands and limbs, causing numbness, weakness and pain. While its exact cause is unknown, GBS often occurs after a gastroenteritis infection called Camplylobacter, with the immune system mistakenly attacking nerves rather than germs.

GBS is usually reversible, however in severe cases it can cause prolonged paralysis involving breathing muscles, require ventilator support and sometimes leave permanent neurological deficits. Early recognition by expert neurologists is key to proper treatment.

Historical context of virus- and vaccine-associated GBS

More cases of GBS were associated with the Zika virus outbreaks in Latin America (2016 and 2020) than expected by chance alone; and concerns have been raised in GBS research reports that a similar link may potentially exist between COVID-19 infection and GBS too.

Researchers also say fears of a global rise in GBS following mass vaccination may persist due to a historic small increase in GBS associated with the 1976 swine flu vaccination campaign in the USA. This vaccination campaign was halted because the risk of developing GBS was statistically increased from background, although subsequent statistical analysis found the risk of a link to be lower than initially thought. In every flu vaccination campaign since, the risk of GBS as a result of flu vaccination is estimated to be about one per million vaccination doses.

This study

In this epidemiological and cohort study, UCL researchers sought to investigate any causative association between COVID-19 infection and GBS.

The team assessed the number of GBS treatments reported to the NHS England National Immunoglobulin Database between 2016 and 2019. This was compared to the number of cases reported during the COVID-19 pandemic in the first half of 2020.

The annual incidence of GBS treated in UK hospitals between 2016 and 2019 was 1.65-1.88 per 100,000 individuals. Incidences of GBS fell 40-50% between March and May 2020 when compared to the same months of 2016-2019. This new finding contradicts that of other smaller and less extensive international studies.

First author, Dr Stephen Keddie (UCL Queen Square Institute of Neurology) said: "The possibility of SARS-CoV-2 driving a global spike in GBS has been eagerly monitored with a number of published small case series already asserting a causal link. However, a surge in GBS cases after the SARS-CoV-2 pandemic has not been detected as happened in the Zika virus pandemic.

"Our epidemiological study shows there was no increased incidence in GBS during the first wave of COVID-19; rather, there was a decrease and therefore no causal link of COVID-19 to GBS can be made."

Separately in this study the research team also tried to establish if there was any genetic or protein structure in SARS-CoV-2, the virus that causes COVID-19, which could trigger an immune response causing GBS. Unlike Camplylobacter, which contains human-like antigens causing an autoimmune response, no credible link was found with SARS-CoV-2.

Dr Keddie added: "Most COVID-19 vaccinations are based on the SARS-CoV-2 spike protein, which drives a complex immune response creating antibodies to fight infection.

"Our analysis shows SARS-CoV-2 contains no additional immunogenic material known or proven to drive GBS. Concerns that COVID vaccination might cause GBS in any significant numbers are therefore almost certainly unfounded."

Around 1,500 cases of GBS occur in the UK each year (two per 100,000 population). History suggests, researchers say, that mass vaccination might be blamed for cases of GBS when occurring by chance, particularly with billions of people expected to be immunised globally.

Corresponding author, Professor Michael Lunn (UCL Queen Square Institute of Neurology) said: "When we immunise the population against COVID-19, GBS (and other neurological illnesses) will occur, by chance alone, in the weeks after immunisation, the window for a normal response to the vaccine.

"These cases may cause concern in patients, politicians, and regulators and stoke anti-vaccination concerns, even though it is likely that most, if not all of the cases, will be associated with vaccination by chance alone.

"Such a severe illness may result in suspension or withdrawal of vaccination as a 'knee jerk' safety reaction but this must not happen unless there is a statistically demonstrated link through careful monitoring that is proven. We must accept small risks with any vaccination programme on this scale, and these are far lower than the risk from COVID infection."

Following the first recorded death of an anaesthetist from COVID-19 in the UK in November 2020, a review of available data published in Anaesthesia (a journal of the Association of Anaesthetists) shows that unexpectedly, despite their perceived increased exposure to COVID-19 patients and high-risk procedures, anaesthetists and intensive care doctors appear to be at lower risk of being infected with SARS-CoV-2 and developing COVID-19.

The analysis was carried out by Professor Tim Cook, Consultant in Anaesthesia and Intensive Care Medicine, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK, and School of Medicine, University of Bristol, UK, and Dr Simon Lenanne, General Practitioner, Ross-on-Wye, Herefordshire, UK. The authors undertook the review following the death on November 12, 2020, of anaesthetist Dr Krishnan Subramanian, who was aged 46 years and worked at the Royal Derby Hospital, UK.

"This very sad event is a moment for pause and reflection. Every death is a tragedy, and our first thoughts should be with Dr Subramanian's family, friends and colleagues," say the authors.

Reviewing numerous studies, the authors say that overall, healthcare workers in patient-facing roles are at two- to four-fold increased risk of infection and harm from COVID-19. Household members of healthcare staff are also at increased risk. However, it remains uncertain whether working in a patient-facing healthcare role significantly increases the risk of death from COVID-19.

"Three separate studies from Oxford, Leicester and Birmingham and including more than 20,000 healthcare staff indicate that those working in anaesthesia and intensive care had less than half the risk of infection than physicians dealing with COVID-19 patients on the wards. These studies also found significantly higher rates of infection in both front-line nurses and housekeeping staff compared to anaesthetists and intensivists," say the authors. "And in a study of Scottish of hospital admission of healthcare workers, working in ICU was again associated with approximately half the risk of working in 'front door' roles. Even household contacts of 'front door' healthcare workers had a higher risk of hospital admission than those working in ICU."

The authors also conducted an analysis to explore whether deaths of anaesthetists were lower than expected amongst the general population and amongst healthcare workers. Using data from The Royal College of Anaesthetists census, NHS Digital, the Office of National Statistics, and their own database of healthcare worker deaths the authors compared the expected and observed number of deaths amongst UK anaesthetists/ intensivists with various comparator groups.

Overall deaths amongst anaesthetists and intensivists were disproportionately low - ranging between less than a half to a quarter of expected deaths based on the numbers working in this speciality. The number of deaths expected among anaesthetists, based on representation of anaesthetists among doctors, and COVID-19 related deaths among the general population would be several times higher than the single death recorded so far (3 or 4 in total).

The authors explain: "This analysis indicates that, irrespective of the comparator group used, deaths among anaesthetists and intensivists are notably lower than expected and certainly not high, as some would have predicted."

The authors offer several possible explanations for the lower risk observed. These include better personal protective equipment or better use of it, working in well-ventilated environments and the possibilities that both the patients who are admitted to ICU are less infectious than those on the wards, and that the high risk procedures such as establishing a patient on a ventilator (including intubation) are not as high risk as has been assumed.

The authors say: "This analysis highlights both the relative safety of anaesthetists and intensivists from occupational harm from SARS-CoV-2 and the increased risks for others working on the wards, both in clinical and non-clinical roles."

They conclude: "It is our opinion that those working in anaesthesia and critical care should continue with current practices to maintain their own safety and that of their working environment. A more challenging question is whether some of the procedures that appear to keep anaesthetists and intensivists safe such as high level protective respirators should be extended to general practice and the wards where other healthcare workers are more at risk."

Dr Mike Nathanson, President of the Association of Anaesthetists, said: "The whole profession was saddened to hear of the tragic death of Dr Krishnan Subramanian. It is reassuring to see that, to date, we have lost no further anaesthestists or intensivists to COVID-19 despite their involvement on the front line of battling this pandemic. The death of each healthcare worker has been in our minds, however. This analysis reminds us of the risks, and of factors that may explain why anaesthetists and intensivists appear to have so far largely escaped the worst of this illness. We are not complacent, and we will continue to work for the wellbeing of the anaesthetists and intensivists we represent."

URBANA, Ill. - Carrots are a good source of beta-carotene, which is a precursor of vitamin A. But to get the full health benefits of this superfood, you need an active enzyme to produce this vitamin.

Beta-carotene is the bioactive compound that gives carrots their orange color. Studies with humans and mice show the conversion of beta-carotene to vitamin A reduces "bad" cholesterol in the blood. Thus, beta-carotene can help protect against atherosclerosis development, which leads to the accumulation of fats and cholesterol in our arteries. Atherosclerosis cardiovascular disease is the primary cause of death worldwide, says Jaume Amengual, assistant professor of personalized nutrition in the Department of Food Science and Human Nutrition at University of Illinois.

Amengual and his colleagues conducted two studies to further understand the effects of beta-carotene on cardiovascular health. They confirmed its importance, but identified a critical step in the process.

Beta-carotene converts to vitamin A with the help of an enzyme called beta-carotene oxygenase 1 (BCO1). A genetic variation determines if you have a more or less active version of BCO1. People with a less active enzyme could need other sources for vitamin A in their diet, Amengual says.

The first study, published in the Journal of Nutrition, analyzed blood and DNA samples from 767 healthy young adults aged 18 to 25. As expected the researchers found a correlation between BCO1 activity and bad cholesterol level.

"People who had a genetic variant associated with making the enzyme BCO1 more active had lower cholesterol in their blood. That was our first observation," Amengual notes.

To follow up on these findings, Amengual and his colleagues conducted a second study, published in the Journal of Lipid Research, using mice.

"In the human study, we saw that cholesterol was higher in people who do not produce much vitamin A. To know if that observation has an effect in the long run, we would have to wait 70 years to see if they develop cardiovascular. In real life, that is not doable. That's why we use animals for certain studies, so we can speed up the process," he explains.

"The main findings of the mice study reproduce what we found in humans. We saw that when we give beta-carotene to mice, they have lower cholesterol levels. These mice develop smaller atherosclerosis lesions, or plaques, in their arteries. This means that mice fed beta-carotene are more protected against atherosclerosis than those fed a diet without this bioactive compound," Amengual states.

In the second study, the researchers also investigated the biochemical pathways of these processes, determining where in the body the effect occurs.

"We narrow it down to the liver as the organ in charge of producing and secreting lipoproteins to the bloodstream, including those lipoproteins known as bad cholesterol. We observed that in mice with high levels of vitamin A, the secretion of lipids into the bloodstream slows down," Amengual notes.

Understanding how the BCO1 enzyme relates to cholesterol has important implications. Typically, high beta-carotene levels in the blood are associated with health benefits. But it could also be a sign of a less active BCO1 enzyme that is not converting the beta-carotene we eat into vitamin A.

Up to 50% of the population have the less-active variant of the enzyme, Amengual notes. That means their body is slower at producing vitamin A from a plant source, and they could need to get this nutrient directly from an animal source such as milk, or cheese, for example.

MELVILLE, N.Y., December 11, 2020 -- A lemony scent and light sounds could change the way you feel about yourself.

Previously, researchers have shown that visual and tactile stimulation can change a person's perception of their own body weight. Research being presented by Giada Brianza, of the University of Sussex, has found our hearing and sense of smell can also change how we feel about our self-image, which could help improve healthy behaviors.

The presentation, "Understanding the impact of sound and smell on body image perception," will be a part of the 179th Meeting of the Acoustical Society of America. This session will be presented on Dec. 11 at 12:20 p.m. Eastern U.S. The meeting will be held virtually Dec. 7-10.

To see if sounds could change body image perceptions, the researchers used headphones to alter in real time how patients heard their own footsteps. Heavier bodies produce lower frequency footsteps than lighter bodies, so the researchers thought that changing the sound could alter how a person perceives their own image.

When the researchers played higher-pitch footsteps that sounded like stilettos, the test subjects were walking faster compared with when they heard lower pitch sounds, like the sound boots make.

The researchers also tested how scents could change one's perceived body image. They found exposure to lemon-scented essential oils in combination with high-pitched sounds during the experiments made participants feel lighter than vanilla scents.

These first results in sound-scent body image association are still being studied, but already the power of audio on body image has promising applications. Since negative body image can lead to increased risks for eating disorders, isolation, and emotional distress, finding ways to manipulate self-image could enhance health through promoting better self-image.

The researchers believe that multisensory stimuli -- sound and smell, in particular -- should play a greater role in treating body image diseases, like eating disorders.

A new molecular probe from Stanford University could help reveal how our brains think and remember. This tool, called Fast Light and Calcium-Regulated Expression or FLiCRE (pronounced "flicker"), can be sent inside any cell to perform a variety of research tasks, including tagging, recording and controlling cellular functions.

"This work gets at a central goal of neuroscience: How do you find the system of neurons that underlie a thought or cognitive process? Neuroscientists have been wanting this type of tool for a long time," said Alice Ting, professor of genetics in the Stanford School of Medicine and of biology in the School of Humanities and sciences, whose team co-led this work with the lab of Stanford psychiatrist and bioengineer, Karl Deisseroth.

In proof-of-concept experiments, detailed in a paper published Dec. 11 in Cell, the researchers used FLiCRE to take a snapshot of neural activity associated with avoidance behavior in mice. By coupling the FLiCRE snapshot with RNA sequencing, they discovered that these activated neurons primarily belonged to a single cell type, which was inaccessible using genetic tools alone. They then used FLiCRE in combination with an opsin - a protein for controlling neural activity with light developed by Deisseroth - to reactivate those same neurons a day later, which led the mice to avoid entering a certain room. The brain region the researchers studied, called the nucleus accumbens, is thought to play an important role in human psychiatric diseases, including depression.

Modular molecular technology

FLiCRE is made up of two chains of molecular components that respond to the presence of blue light and calcium. This light sensitivity allows the researchers to precisely control the timing of their experiments, and calcium is an almost-universal indicator of cell activity. To get FLiCRE inside a cell, the researchers package it, in two parts, within a harmless virus. One part of FLiCRE attaches to the cell membrane and contains a protein that can enter the cell's nucleus and drive expression of whatever gene the researchers have selected. The other part of FLiCRE is responsible for freeing the protein under certain specific conditions, namely if the concentration of calcium is high and the cell is bathed in blue light.

Whereas existing tagging techniques require hours to activate, the FLiCRE tagging process takes just minutes. The researchers also designed FLiCRE so that they can use standard genetic sequencing to find the cells in which FLiCRE activated. This allows them to study tens of thousands of cells at once, while other techniques tend to require the analysis of multiple microscopic images that each contain hundreds of cells.

In one series of experiments, the researchers injected FLiCRE into cells in the nucleus accumbens and used an opsin to activate a neural pathway associated with avoidance behavior in the mice. Once the calcium in FLiCRE-containing cells spiked - the cellular indication that the mouse is avoiding something - the cells glowed a permanent red that was visible through a microscope. The researchers also sequenced the RNA of the cells to see which ones contained the fluorescent protein, producing a cell-by-cell record of neural activity.

"One goal was to map how brain regions are connected to each other in living animals, which is a really hard problem," said Christina Kim, a postdoctoral scholar in genetics at Stanford and co-lead author of the paper. "The beauty of FLiCRE is that we can pulse and activate neurons in one region and then record all of the connected downstream neurons. It is a really cool way to look at long-range brain activity connections."

In the next experiments, the researchers used the cellular activity map from the first experiments. They also adjusted FLiCRE so that the protein expressed the opsin protein, which can be controlled by orange light to alter neuronal activity. After activating FLiCRE in the cells, the researchers sent orange light through the fiber optic implant whenever the mice would enter a certain room. In response, the mice steered clear of that room, indicating that FLiCRE had indeed located cells in the brain that drive avoidant behavior.

A dream project

The development and testing of FLiCRE combined chemistry, genetics, biology and neuroscience, and many specialties within those disciplines. As a result, the tool has a wide range of possible applications, including in cells outside the brain, the researchers say.

"I moved to Stanford in 2016 with the hope of being able to carry out extremely interdisciplinary and collaborative projects such as this," said Ting. "This project has been one of the most rewarding aspects of my move to Stanford - seeing something this challenging and ambitious actually work out."

The researchers are now working on additional versions of FLiCRE, with a goal of streamlining the process. They are hoping to simplify its structure and also make it capable of working with other biochemical events, such as protein interactions or neurotransmitter release.

Potential treatments for Covid-19 have been identified after the discovery of five genes associated with the most severe form of the disease.

Genetic evidence is second only to clinical trials as a way to tell which treatments will be effective in a disease. Existing drugs that target the actions of the genes reveal which drugs should be repurposed to treat Covid-19 in clinical trials, experts say.

Genes involved in two molecular processes - antiviral immunity and lung inflammation - were pinpointed. The breakthrough will help doctors understand how Covid-19 damages lungs at a molecular level.

Researchers from the University of Edinburgh made the discovery by studying the DNA of 2,700 patients in 208 intensive care units (ICUs) in the UK.

Researchers from the GenOMICC consortium - a global collaboration to study genetics in critical illness - compared the genetic information of Covid-19 patients in ICU with samples provided by healthy volunteers from other studies, such as UK Biobank, Generation Scotland and 100,000 Genomes.

The team found key differences in five genes of the ICU patients compared with samples provided by healthy volunteers. The genes - IFNAR2, TYK2, OAS1, DPP9 and CCR2 - partially explain why some people become desperately sick with Covid-19, while others are not affected.

Having highlighted the genes, the team were then able to predict the effect of drug treatments on patients, because some genetic variants respond in a similar way to particular drugs.

For example, they showed that a reduction in the activity of the TYK2 gene protects against Covid-19. A class of anti-inflammatory drugs called JAK inhibitors, which includes the drug baricitinib, produces this effect.

They also discovered that a boost in the activity of the gene INFAR2 is also likely to create protection, because it is likely to mimic the effect of treatment with interferon - proteins released by cells of the immune system to defend against viruses. However, experts caution that to be effective, patients might need the treatment early in disease.

Based on the findings published in Nature, the researchers say that clinical trials should focus on drugs that target these specific antiviral and anti-inflammatory pathways.

Dr Kenneth Baillie, the project's chief investigator and Academic Consultant in Critical Care Medicine and Senior Research Fellow at University of Edinburgh's Roslin Institute, said: "This is a stunning realisation of the promise of human genetics to help understand critical illness. Just like in sepsis and influenza, in Covid-19, damage to the lungs is caused by our own immune system, rather than the virus itself. Our genetic results provide a roadmap through the complexity of immune signals, showing the route to key drug targets.

"Our results immediately highlight which drugs should be at the top of the list for clinical testing. We can only test a few drugs at a time, so making the right choices will save thousands of lives.

"This work is only possible because of the generous contribution of the patients themselves and their families, research teams in NHS hospitals across the country, and the generous funding we've received from the public and organisations."

GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) started in 2015 as an open, global consortium of intensive care clinicians dedicated to understanding genetic factors that influence outcomes in intensive care from diseases such as SARS, influenza and sepsis. Throughout 2020 it has been focused on Covid-19 research in partnership with Genomics England.

PRINCETON, N.J.--The rise of populist movements is changing political systems around the world. As support for these "anti-elite" movements intensifies, many are scrambling to understand whether economic decline and intensifying inter-group conflict are playing a role.

A model developed by a team of researchers -- including Nolan McCarty of Princeton University -- shows how group polarization, rising inequality, and economic decline may be strongly connected.

The model develops a theory that group polarization tends to soar in times of economic duress and rising inequality. Yet, even after financial conditions improve, these divisions may remain deeply rooted.

This is why strengthened social safety nets are needed to help minimize conflict across social, ethnic, and racial groups, the researchers argue in Science Advances.

"Times arise when national unity is needed, like we're seeing now with Covid-19, but we shouldn't wait for a public health crisis or war to bring people together. Policymakers and those in government should act now by investing in and protecting social safety nets that can prevent widening social and political divisions," said McCarty, who is the Susan Dod Brown Professor of Politics and Public Affairs at the Princeton School of Public and International Affairs.

McCarty worked on the model with Alexander Stewart of the University of Houston and Joanna Bryson of the Hertie School in Berlin, Germany. Using models of cultural evolution and evolutionary game theory, the team designed their model to examine people's willingness to interact with people outside their own social group.

The model is based on a few assumptions -- the first being that an individual's economic success is tied to interactions with others and the performance of the underlying economy. They also assume that people tend to mimic the behavior of seemingly "successful" people so that social behaviors can spread through the public.

Lastly they assume that interactions within social in-group behavior is generally less risky with lower rewards while interactions with out-group members are more risky, but entail greater upside. This means that when economic conditions become more challenging, people will tend to prefer the safe bet of interacting with their own kind and avoid interactions with outsiders. As such behavior is mimicked, the interactions across groups declines precipitously.

The model may be helpful in explaining political trends seen around the world. First, the model supports theories arguing that economic shocks embolden those far-right movements predicated vilifying social out-groups. For example, the Great Depression and Global Financial Crisis both led to increased support for right-wing populists in a number of countries including the United States, and the United Kingdom.

When it comes to inequality, most models suggest that a significant wealth gap tends to empower those on the left, as they will seek income redistribution. The researchers' new model doesn't necessarily show such a shift, but instead a general move away from interactions across social identity groups. Since cross-group interactions are economically valuable, society gets poorer.

"Rather than continue the unproductive debate over whether 'economic anxiety' or group conflict is most responsible for our deeply divided politics, scholars should spend more effort considering the debilitating feedback between economics and identity," said McCarty.