Culture

Researchers develop more reliable rapid tests for COVID-19

Researchers at the University of Maryland School of Medicine (UMSOM) have developed two rapid diagnostic tests for COVID-19 that are nearly as accurate as the gold-standard test currently used in laboratories. Unlike the gold standard test, which extracts RNA and uses it to amplify the DNA of the virus, these new tests can detect the presence of the virus in as little as five minutes using different methods.

One test is a COVID-19 molecular diagnostic test, called Antisense, that uses electrochemical sensing to detect the presence of the virus. The other uses a simple assay of gold nanoparticles to detect a color change when the virus is present. Both tests were developed by Dipanjan Pan, PhD, Professor of Diagnostic Radiology and Nuclear Medicine and Pediatrics at UMSOM and his research team. Dr. Pan has a joint appointment at the University of Maryland Baltimore County (UMBC).

"These tests detect the presence of the virus within 5 to 10 minutes and rely on simple processes that can be performed with little lab training," said Dr. Pan. They do not require the extraction of the virus's RNA - which is both complicated and time consuming.

They also are more reliable than the rapid antigen tests currently on the market, which detect the virus only in those with significantly high viral levels. "These two newer tests are extremely sensitive and can detect the presence of the virus, even in those with low levels of the virus," Dr. Pan said.

Dr. Pan's team included UMSOM research fellow Maha Alafeef, UMSOM research associate Parikshit Moitra, PhD, and research fellow Ketan Dighe, from UMBC.

Last month, the U.S. Food and Drug Administration (FDA) registered the laboratory of Dr. Pan as an approved laboratory development site for the Antisense test. The move paves the way for Dr. Pan's laboratory to begin conducting the test at the university, in research settings, as it undergoes further development.

In February, RNA Disease Diagnostics, Inc. (RNADD) received an exclusive global license from UMB and UMBC to commercialize the test. Dr. Pan serves as an unpaid scientific advisor to the company.

This test detects the virus in a swab sample using an innovative technology called electrochemical sensing. It uses a unique dual-pronged molecular detection approach that integrates electrochemical sensing to rapidly detect the SARS-CoV-2 virus.

"The final prototype is like a glucometer, which patients with diabetes use at home to measure their blood glucose levels," said Dr. Pan, "and is just as easy for people to do themselves."

Dr. Pan and his colleagues, in collaboration with RNA Disease Diagnostics, are launching a study of NBA basketball players in New York City to compare the Antisense test to rapid COVID tests that the NBA is using to monitor COVID infections in its players.

"We would like to see whether our test can yield more reliable results compared to the existing platforms," he said. "Current antigen-based rapid COVID tests miss infections about 20 percent of the time and also have high rates of false positive results. Our Antisense test appears to be about 98 percent reliable, which is similar to the PCR test."

Similar to the Antisense test, the second rapid test also does not require the use of any advanced laboratory techniques, such as those commonly used to extract RNA, for analysis. It uses a simple assay containing plasmonic gold nanoparticles to detect a color change when the virus is present. In April, Dr. Pan and his colleagues published a stepwise protocol in the journal Nature Protocols, explaining how the nano-amplified colorimetric test works and how it can be used.

Once a nasal swab or saliva sample is obtained from a patient, the nucleic acid (bits of genetic material) in the sample is amplified via a simple process that takes about 10 minutes. The test uses a highly specific molecule attached to the gold nanoparticles to detect a particular protein. This protein is part of the genetic sequence that is unique to the novel coronavirus. When the biosensor binds to the virus's gene sequence, the gold nanoparticles respond by turning the liquid reagent from purple to blue.

"Innovations in COVID-19 testing remain incredibly important even as the epidemic appears to be waning in this country," 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. "As we continue to monitor infections in unvaccinated segments of our population and the potential spread of new variants, there will be a vital need for inexpensive rapid tests to ensure that we continue to maintain low infection rates."

Credit: 
University of Maryland School of Medicine

Researchers 3D print rotating microfilter for lab-on-a-chip applications

image: Researchers fabricated tiny magnetically driven rotating filters for use in microfluidic channels. The filters are just 70 microns wide and 60 microns tall with square openings that measure 6.5 microns on each side. Scale bar: 10 microns

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Dong Wu, University of Science and Technology of China

WASHINGTON -- Researchers have fabricated a magnetically driven rotary microfilter that can be used to filter particles inside a microfluidic device. They made the tiny turning filter by creating a magnetic material that could be used with a very precise 3D printing technique known as two-photon polymerization.

Microfluidic devices, also known as lab-on-a-chip devices, can be used to perform multiple laboratory functions inside a chip that usually measures a few square centimeters or less. These devices contain intricate networks of microfluidic channels and are becoming more and more complex. They may be useful for a variety of applications such as screening molecules for therapeutic potential or performing blood tests that detect disease.

"By changing the direction of external magnetic field, the microfilter we made can be remotely manipulated on demand to either filter certain-sized particles or to allow them all to pass," said Dong Wu, a member of the research team from the University of Science and Technology of China. "This functionality could be used for many types of chemical and biological studies performed in lab-on-a-chip devices and, importantly, makes it possible for the chips to be reused."

In The Optical Society (OSA) journal Optics Letters, Wu together with colleagues from the Hefei University of Technology and RIKEN Center for Advanced Photonics in Japan show that their new rotary microfilter filters can sort particles in a microfluidic device with high performance.

"This filter could eventually be used to sort cells of different sizes for applications such as isolating circulating tumor cells for analysis or detecting abnormally large cells that may indicate disease," said Chaowei Wang from University of Science and Technology of China. "With further development it might even be possible to use it in devices placed inside the body for cancer detection."

A more versatile filter

Filters with micrometer-sized holes are often used in microfluidic chips as a passive way to sort particles or cells based on sizes of the holes. However, because the number and shape of holes in the filter cannot be dynamically changed, available devices lack the flexibility to sort different types of particles or cells on demand. To expand the usefulness of microfluidic devices, the researchers developed a filter that can freely switch between modes such as selective filtering and passing.

They created the new filter using two-photon polymerization, which uses a focused femtosecond laser beam to solidify, or polymerize, a liquid light-sensitive material known as photoresist. Thanks to two-photon absorption, the polymerization can be done in a very precise manner, enabling fabrication of complex structures on the micron scale.

To make the microfilter, the researchers synthesized magnetic nanoparticles and mixed them with the photoresist. Fabricating the rotary microfilter required them to optimize the laser power density, number of pulses and scanning intervals used for polymerization. After testing its magnetically driven properties on a glass slide, they integrated the microfilter into a microfluidic device.

Multiple filtering modes

To filter larger particles, a magnetic field perpendicular to the microchannel is applied. After the filtering process is complete, the large particles can be released by applying a magnetic field that is parallel to the microchannel, which will rotate the microfilter by 90°. The filtering process can then be repeated as needed.

The researchers verified the filtering performance of the filter using polystyrene particles with diameters of 8.0 and 2.5 microns that were mixed in an alcohol solution. "It was clear that particles smaller than the pore size easily passed through microfilter while bigger ones were filtered out," said Chenchu Zhang from University of Science and Technology of China. "When in passing mode, any larger particles captured by the filter were washed away with the fluid, which prevents filter clogging and allows reuse of the microfilter."

Credit: 
Optica

Early encounter of microbes and fetal immune system during second trimester of gestation

image: Using a combination of complementary approaches, Mishra et al identified the presence of live microbes in healthy human fetal tissues that prime T-cell during second trimester of gestation.

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Image may only be used with appropriate credit.

2 June 2021, Singapore - The human fetal immune system begins to develop early during gestation, however, factors responsible for fetal immune-priming remain elusive. Using multiple complementary approaches, Dr Florent Ginhoux from A*STAR's Singapore Immunology Network (SIgN), Professor Jerry Chan from KK Women's and Children's Hospital (KKH), Professor Salvatore Albani from the SingHealth Duke-NUS Translational Immunology Institute, with collaborators from Cambridge University explored potential exposure to microbial agents in-utero. The team identified live microbes across fetal organs that stimulate activation of fetal T-cells during the second trimester of gestation. Study published in scientific journal, Cell, on 24 June 2021.

The team profiled microbes across fetal organs using 16S-rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta and lungs, in the second trimester of gestation. They identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T-cells in fetal mesenteric lymph-node, supporting the role of microbial exposure in fetal immune-priming. Finally, using scanning electron microscope (SEM) and Ribonucleic acid (RNA) in situ hybridisation (RNA-ISH), discrete localisation of bacteria-like structures and eubacterial-RNA were visualised within the 14th week fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during second trimester of gestation and have broader implications on the establishment of immune competency and priming before birth.

The findings demonstrate that healthy human fetal tissues (in the second trimester of gestation) contain effector memory T-cells, a sparse biomass of bacteria and an active memory T-cell response towards fetal bacteria. It also demonstrates direct spatial localisation of bacterial entities, localised within the lumen of developing fetal gut, during second trimester of gestation.

Dr Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said, "Our study demonstrates that such microbial presence primes the fetal immune system, thereby putting early microbial memory in the context of fetal immune priming, a concept not explored before in fetal immunity. It will be interesting to explore the precise nature of these microbial antigen-specific circulatory and immune cells that reside in human fetal organ tissues, and their potential role in imparting selective defence against pathogenic microbes in neonatal and adult life. Taken together, these findings have wider implications in understanding the key factors involved in fetal immune system development and priming in utero, which may set the basis for life-long human health and immunity of the organism."

Credit: 
Agency for Science, Technology and Research (A*STAR), Singapore

Strict rest after sports-related concussion slows recovery and may prolong symptoms

Persisting symptoms thought to be complex interplay between effects of new injury and underlying conditions

Strict rest after a sports related concussion slows recovery and may prolong symptoms, says a consensus statement drawn up by a US expert panel on how best to treat and manage the condition, and published in the British Journal of Sports Medicine.

Most of these concussions get better within a month and can be effectively treated, it says.

Persisting symptoms are thought to be a complex interplay between the physical and psychological effects of the new injury and underlying conditions.

The consensus statement was developed by the Team Physician Consensus Conference (TPCC), an annual project-based alliance of six major professional associations,* with the aim of helping team doctors to provide the best medical care for athletes.

It updates a previous version on the management of concussion, published in 2011.

Data harvested from US emergency department visits, doctors' appointments, and a high school injury surveillance system (RIO) estimate the number of sports related concussions to be between 1 and 1.8 million every year in the USA alone among those up to the age of 18, with around 400,000 occurring in high school athletes.

But the symptoms of concussion aren't specific and there are currently no clinically useful diagnostic tests, such as blood tests, genetic tests or standard imaging techniques. So the true incidence and prevalence of sports related concussion remain unknown, says the statement.

Signs and symptoms indicating more severe brain or neck (cervical spine) injury and warranting immediate emergency care include:

Immediate seizure (at or minutes after impact)

More than brief loss of consciousness

Severe or worsening headache

Persistent or recurrent vomiting

Increasing lethargy, confusion

Tingling or numbness in hands and/or feet; double vision

Neck pain; bony tenderness; limited range of movement and/or deformity

And there is a range of symptoms that may occur immediately or some time later, which may also be indicative of concussion, says the statement.

These include: amnesia; disorientation; brain fog; inability to focus; slurred speech; excessive drowsiness; headache; dizziness; balance issues; visual disturbances; hypersensitivity to noise; irritability; and sleep disturbances.

Most sports related concussion is treatable, says the statement. And most affected athletes will recover fully within 2 (adults) to 4 weeks (children).

The number and severity of the initial array of symptoms best predict how long it will take to recover.

Factors that may prolong or complicate recovery include: previous concussions; loss of consciousness for more than 1 minute; younger age; pre-existing conditions, including migraine, ADHD, learning disabilities, depression, anxiety/panic attacks, and motion sickness.

Current evidence suggests that strict rest after a concussion slows recovery and increases the probability of prolonged symptoms. Recent research shows that progressive moderate aerobic exercise within the first week helps aid recovery.

Most athletes don't require over-the-counter and/or prescription meds for acute symptoms. And there's no current evidence to suggest that 'nutraceuticals' help to either ward off or treat concussion, says the statement.

Persisting symptoms, such as fatigue, headache, and anxiety, aren't usually caused by one factor alone, but are thought to be a complex interplay between the physical and psychological effects of the new injury and underlying conditions, says the statement.

In these circumstances, treatment should focus on the particular symptom: cognitive behavioural therapy and/or lifestyle changes to sleep, nutrition, and hydration, for example.

More high quality research is needed to fully understand young people's risks of taking part in sport after concussion and the effects on their long term brain health and wellbeing, says the statement.

"Most athletes who have been concussed will get better, and will be able to return to play," comments Dr Margot Putukian, TPCC executive committee member.*

"Each injury is unique and will have its own timeline. But athletes should take comfort in knowing that there are treatments out there, and there are steps they can take to aid their own recovery, she adds.

Credit: 
BMJ Group

Over half of cardiovascular disease deaths worldwide occur in Asia

The number of people dying from cardiovascular disease (CVD) in Asia is increasing rapidly, with over half of all CVD deaths globally in 2019 occurring in Asian countries, according to a state-of-the-art review paper published in the inaugural issue of JACC: Asia. The data demonstrates an urgent need to understand the burdens and epidemiological features of CVD in Asian countries to develop localized CVD prevention strategies to combat the epidemic.

From 1990 to 2019, the number of CVD deaths in Asia rose from 5.6 million to 10.8 million. Nearly 39% of these CVD deaths were premature, meaning they occurred in a person less than 70 years old, which was significantly higher than premature CVD deaths in the U.S. (23%). Most CVD deaths were due to ischemic heart disease (IHD) or stroke. According to the researchers, increasing CVD epidemics in Asia are due to demographic changes, socioeconomics, living environments, lifestyles, prevalence of CVD risk factors and capacities to prevent and treat CVD.

In this paper, authors reviewed data on CVD epidemiology in Asian countries from multiple sources and identified five epidemiological features in Asia: continuously increasing CVD mortality rate; geographic differences in CVD mortality; regional differences in the dominant CVD subtype; countries that are in different transition stages of the CVD epidemic; and the increasing epidemics and massive burdens of key modifiable CVD risk factors in most countries with inadequate capacities for management.

"Timely information on the burdens and epidemiological features of CVD in Asian countries is crucial to understanding the challenges and orienting the development of reasonable policies strategies and actions to combat the CVD epidemic," said Dong Zhao, MD, PhD, professor of preventive cardiology at the Beijing Institute of Heart, Lung and Blood Vessel Diseases at Beijing Anzhen Hospital, Capital Medical University, and a deputy editor of JACC: Asia.

From 1990-2019, the proportion of CVD deaths among total deaths in Asia increased from 23% to 35%, and crude CVD mortality rates grew in both men and women. The rising crude CVD mortality rates indicate the increasing burden of CVD in Asian populations.

There were significant geographic differences in crude CVD mortality rates among Asian countries in 2019. The highest CVD mortality rate in Asia was in Georgia (810.7 per 100,000 population) and the lowest was in Qatar (39.1 per 100,000 population), representing a 20-fold difference.

While IHD and stroke are the most common causes of CVD in Asia, epidemics of these two types of CVD varied substantially between Asian regions and countries. IHD was the most dominant cause of CVD deaths in Central, Western and Southern Asia, whereas deaths from stroke were more common than IHD deaths in Eastern and Southeastern Asia. In China, the dominant subtype of CVD deaths has shifted from stroke to IHD. According to the authors, the underlying cause of the differences in the dominant CVD subtypes among Asian regions or countries is still not well understood.

The paper also compared the characteristics of CVD spectrums (the distributions of relevant disease categories in total deaths) in low-, middle- and high-income (or developed) Asian countries since countries at different stages of economic development may feature different transition stages of the CVD epidemic.

"It is critical to recognize the characteristics of different transition stages of the CVD epidemic in different Asian countries in order to guide the identification of priority issues in public health, resource allocation and research in these countries," Zhao said.

Most Asian countries are in the second stage of the rapidly increasing CVD epidemic. In these countries like China, CVD mortality rates are relatively high, with the proportion of CVD deaths among total deaths generally greater than 40%. Characteristics of CVD epidemics in high-income or developed countries feature the third stage of the epidemiological transition, with lower proportions of CVD deaths. In Japan and South Korea, the proportions of CVD deaths among total deaths decreased from 34.9% and 36.2% in 1990, to 26.6% and 24.3% in 2019, respectively.

According to the researchers, the increasing prevalence of CVD risk factors is a major modifiable cause of the rising CVD epidemics in Asia. These risk factors include dietary, smoking, dyslipidemia, diabetes and hypertension, among many others.

"The information summarized in this review provides a complete picture of CVD epidemiology in Asia, highlighting specific requirements for the development of localized CVD prevention strategies and research, and may illuminate not only the current but also future challenges faced by different Asian countries," Zhao said.

Credit: 
American College of Cardiology

Research papers that omit 'mice' from titles receive misleading media coverage

image: Omitting mice from the paper's title: are scientists ignoring a relevant caveat?

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Image by sibya from Pixabay

There is increasing scrutiny around how science is communicated to the public, but what is the relationship between how scientists report their findings and how media reports it to the public? A study published in PLOS Biology by Marcia Triunfol at Humane Society International, in Washington, DC and Fabio Gouveia at Oswaldo Cruz Foundation in Rio de Janeiro, Brazil suggests that when authors of scientific papers omit the basic fact that a study was conducted in mice (and not in humans) from the article title, journalists reporting on the paper tend to do the same.

Alzheimer's Disease is an exclusively human condition that does not occur naturally in other species, but around 200 rodent models have been developed to study it. News stories frequently lead with headlines omitting that Alzheimer's Disease research findings are based on research using mice, not humans.

To test the hypothesis that how scientists report their research plays a role in the news reporting, the researchers analyzed 623 scientific papers published in 2018 and 2019 that used mice either as models or as the biological source for experimental studies in Alzheimer's Disease research. They then divided the papers into two groups; those that declared in their titles that mice were the study's main species, and those that omitted mice from the paper's title. The authors analyzed whether there was any difference between these groups regarding the number of news stories each paper generated.

The researchers found an association between articles' titles and news stories' headlines, suggesting that journalists tend to follow authors' decision to omit the species studied in the paper's title. They also found that papers not mentioning mice in their titles receive more press coverage and are significantly more highly tweeted than papers that do. The study had several limitations, including that the articles analyzed only included open access publications. Additionally, findings cannot be extended to other fields before a careful analysis is done.

According to the authors, "To our knowledge, this is the first study to present scientific evidence that the way science is reported by scientists plays a role in how journalists report science news. News stories' headlines that omit mice as the main study subject may mislead the public regarding the actual state of affairs in Alzheimer's Disease research while raising false hopes for patients and their families".

Dr. Triunfol notes, "We need to remember that most people only read the headlines of news stories. Thus, if the headline omits that the Alzheimer's study was done in mice, most keep the impression that the study findings apply to humans, which is not true. We now know that virtually all findings obtained in animal studies in Alzheimer's Disease do not replicate to humans".

Dr. Triunfol adds, "In a follow up study we will investigate why scientists choose to omit mice from their studies' titles. In this article we raised some hypothesis".

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PLOS

Drone footage reveals social secrets of killer whales

image: Killer whales making contact with each other

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University of Exeter

Killer whales have complex social structures including close "friendships", according to a new study that used drones to film the animals.

The findings show that killer whales spend more time interacting with certain individuals in their pod, and tend to favour those of the same sex and similar age.

The study, led by the University of Exeter and the Center for Whale Research (CWR), also found that the whales become less socially connected as they get older.

"Until now, research on killer whale social networks has relied on seeing the whales when they surface, and recording which whales are together," said lead author Dr Michael Weiss, of the University of Exeter.

"However, because resident killer whales stay in the social groups into which they're born, how closely related whales are seemed to be the only thing that explained their social structure.

"Looking down into the water from a drone allowed us to see details such as contact between individual whales.

"Our findings show that, even within these tight-knit groups, whales prefer to interact with specific individuals.

"It's like when your mom takes you to a party as a kid - you didn't choose the party, but you can still choose who to hang out with once you're there."

Patterns of physical contact - one of the social interactions the study measured - suggest that younger whales and females play a central social role in the group. The older the whale, the less central they became.

The new research built on more than four decades of data collected by CWR on southern resident killer whales, a critically endangered population in the Pacific Ocean.

"This study would not have been possible without the amazing work done by CWR," said Professor Darren Croft, of Exeter's Centre for Research in Animal Behaviour.

"By adding drones to our toolkit, we have been able to dive into the social lives of these animals as never before.

"We were amazed to see how much contact there is between whales - how tactile they are.

"In many species, including humans, physical contact tends to be a soothing, stress-relieving activity that reinforces social connection.

"We also examined occasions when whales surfaced together - as acting in unison is a sign of social ties in many species.

"We found fascinating parallels between the behaviour of whales and other mammals, and we are excited about the next stages of this research."

Credit: 
University of Exeter

Anti-inflammatory effects of omega-3 fatty acids could help reduce depression

The omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in oily fish. Researchers from the National Institute of Health Research (NIHR) Maudsley Biomedical Research Centre assessed the effects of high doses of EPA and DHA in lab-grown neurones and then in patients to help clarify how they reduce inflammation and depression. This novel approach allowed the scientists to identify an important molecular mechanism which can help inform the development of potential new treatments involving omega-3 fatty acids for patients with depression.

Lead author Dr Alessandra Borsini, NIHR Maudsley BRC Senior Postdoctoral Neuroscientist at King's College London, said: "Using a combination of laboratory and patient research our study has provided exciting new insight into how omega-3 fatty acids bring about anti-inflammatory effects that improve depression. For some time we have known that omega-3 PUFA can induce anti-depressant and anti-inflammatory effects but, without further understanding of how this happens in the human brain, it has been difficult to develop treatments. Our study has helped shine a light on the molecular mechanisms involved in this relationship which can inform the development of potential new treatments for depression using omega-3 PUFA."

Previous research has shown that people with major depressive disorder have higher levels of inflammation in their bodies than those without the disorder. There are currently no proven anti-inflammatory treatment strategies for depression and, although two important omega-3 PUFAs, EPA and DHA, have been shown to provide anti-inflammatory and antidepressant effects, the precise mechanism by which they do this is unknown.

Depression in a dish
The study set out to test the theory that when omega-3 fatty acids are utilised and processed in the body, some of their metabolites (known as lipid mediators) are able to protect the brain from the harmful effects of inflammation. Researchers used a validated in vitro human cell model known as 'depression in a dish' that was developed at the NIHR Maudsley Biomedical Research Centre and which uses cells from the hippocampus, a part of the brain fundamental in many cognitive, memory and learning areas thought to be important in depression. Hippocampal cells play an important role in the production of new neurones - neurogenesis.

The study showed that treating human hippocampal cells with EPA or DHA before being exposed to chemical messengers involved in inflammation called cytokines, prevented increased cell death and decreased neurogenesis. Both these impacts had been previously observed in cells exposed to cytokines alone. Further investigation confirmed these effects were mediated by the formation of several key lipid mediators produced by EPA and DHA, namely hydroxyeicosapentaenoic acid (HEPE), hydroxydocosahexaenoic acid (HDHA), epoxyeicosatetraenoic acid (EpETE) and epoxydocosapentaenoic acid (EpDPA), and these were detected for the first time in human hippocampal neurones. Further investigation showed that treatment with an enzyme inhibitor increased the availability of two of these metabolites (EpETE and EpDPA) suggesting a possible way by which future treatments could be optimised.

Professor Anna Nicolaou, professor of Biological Chemistry at the Faculty of Medical and Human Sciences, The University of Manchester, who led the team that measured the lipid mediators using mass spectrometry said: "The lipid mediators that our research identified are broken down in the body relatively quickly, which means they may only be available for a relatively short time. By testing the effect of inhibitors of the enzymes involved in the metabolism of omega-3 PUFA we showed that we can greatly improve how long they can have an effect in the body and ultimately, increase their efficacy. This is very important for the development of new treatments and means that patients could be given higher doses of EPA and DHA together with these enzyme inhibitors to increase the amount of these important compounds in their blood over time."

Omega-3 metabolites in patients

The study assessed twenty-two patients with major depression who were given either 3 grams of EPA or 1.4 grams of DHA daily for twelve weeks. The lipid metabolites of EPA and DHA were measured in their blood before and after the omega-3 PUFA treatment, along with a score of their depressive symptoms. In both groups of patients, EPA or DHA treatment was associated with an increase in their respective metabolites and a significant improvement in depressive symptoms - an average reduction in symptom scores of 64% and 71% in the EPA and DHA groups respectively. In addition, higher levels of the same metabolites identified in the in vitro experiments were correlated with lower levels of depressive symptoms.

The levels of EPA and DHA used in this study are concentrations that most likely cannot be achieved with dietary consumption of oily fish, a rich source of omega-3 PUFAs, but require therapeutic supplements.

Future Research

The results of the study indicate that the bioactive lipid mediators produced by the breakdown of EPA and DHA in the body could be targeted as a mechanism to reduce depression and inflammation but there is a need to ensure that their effects are prolonged in order for this approach to be successful. Previous research indicates a key enzyme in the omega-3 fatty acid metabolism could be a valid option for drug repurposing and could be used for other inflammation-associated brain disorders, including depression, where at least a sub-group of patients often have chronic levels of inflammation.

Senior author of the paper, Professor Carmine Pariante, NIHR Maudsley BRC Affective Disorders Interface with Medicine Theme Lead said: "There is ever growing interest in the links between the immune system, inflammation and depression but in order to develop new treatments in this area we need to better understand the mechanisms behind these relationships. Our study has provided important insight into how known anti-inflammatory compounds - the omega-3 PUFA - help reduce depression. By identifying and measuring the exact lipid mediators that are involved, identifying the enzyme that prolongs their effects and finding the same lipid mediators in depressed patients treated with omega-3 PUFA and demonstrating improvements in symptoms, we have provided vital information to help shape clinical trials for future therapeutic approaches with omega-3 fatty acids.

"It is important to highlight that our research has not shown that by simply increasing omega-3 fatty acids in our diets or through taking nutritional supplements we can reduce inflammation or depression. The mechanisms behind the associations between depression and omega-3 PUFA are complicated and require further research and clinical trials to fully understand how they work and inform future therapeutic approaches."

The study was a collaboration between researchers from King's College London, The University of Manchester and China Medical University.

The paper Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis was published today (Wednesday 16 June) in Molecular Psychiatry.

Credit: 
King's College London

Greater than the sum of our parts: The evolution of collective intelligence

The period preceding the emergence of behaviourally modern humans was characterised by dramatic climatic and environmental variability - it is these pressures, occurring over hundreds of thousands of years that shaped human evolution.

New research published today in the Cambridge Archaeological Journal proposes a new theory of human cognitive evolution entitled 'Complementary Cognition' which suggests that in adapting to dramatic environmental and climactic variabilities our ancestors evolved to specialise in different, but complementary, ways of thinking.

Lead author Dr Helen Taylor, Research Associate at the University of Strathclyde and Affiliated Scholar at the McDonald Institute for Archaeological Research, University of Cambridge, explained: "This system of complementary cognition functions in a way that is similar to evolution at the genetic level but instead of underlying physical adaptation, may underlay our species' immense ability to create behavioural, cultural and technological adaptations. It provides insights into the evolution of uniquely human adaptations like language suggesting that this evolved in concert with specialisation in human cognition."

The theory of complementary cognition proposes that our species cooperatively adapt and evolve culturally through a system of collective cognitive search alongside genetic search which enables phenotypic adaptation (Darwin's theory of evolution through natural selection can be interpreted as a 'search' process) and cognitive search which enables behavioural adaptation.

Dr Taylor continued, "Each of these search systems is essentially a way of adapting using a mixture of building on and exploiting past solutions and exploring to update them; as a consequence, we see evolution in those solutions over time. This is the first study to explore the notion that individual members of our species are neurocognitively specialised in complementary cognitive search strategies."

Complementary cognition could lie at the core of explaining the exceptional level of cultural adaptation in our species and provides an explanatory framework for the emergence of language. Language can be viewed as evolving both as a means of facilitating cooperative search and as an inheritance mechanism for sharing the more complex results of complementary cognitive search. Language is viewed as an integral part of the system of complementary cognition.

The theory of complementary cognition brings together observations from disparate disciplines, showing that they can be viewed as various faces of the same underlying phenomenon.

Dr Taylor continued: "For example, a form of cognition currently viewed as a disorder, dyslexia, is shown to be a neurocognitive specialisation whose nature in turn predicts that our species evolved in a highly variable environment. This concurs with the conclusions of many other disciplines including palaeoarchaeological evidence confirming that the crucible of our species' evolution was highly variable."

Nick Posford, CEO, British Dyslexia Association said, "As the leading charity for dyslexia, we welcome Dr Helen Taylor's ground-breaking research on the evolution of complementary cognition. Whilst our current education and work environments are often not designed to make the most of dyslexia-associated thinking, we hope this research provides a starting point for further exploration of the economic, cultural and social benefits the whole of society can gain from the unique abilities of people with dyslexia."

At the same time, this may also provide insights into understanding the kind of cumulative cultural evolution seen in our species. Specialisation in complementary search strategies and cooperatively adapting would have vastly increased the ability of human groups to produce adaptive knowledge, enabling us to continually adapt to highly variable conditions. But in periods of greater stability and abundance when adaptive knowledge did not become obsolete at such a rate, it would have instead accumulated, and as such Complementary Cognition may also be a key factor in explaining cumulative cultural evolution.

Complementary cognition has enabled us to adapt to different environments, and may be at the heart of our species' success, enabling us to adapt much faster and more effectively than any other highly complex organism. However, this may also be our species' greatest vulnerability.

Dr Taylor concluded: "The impact of human activity on the environment is the most pressing and stark example of this. The challenge of collaborating and cooperatively adapting at scale creates many difficulties and we may have unwittingly put in place a number of cultural systems and practices, particularly in education, which are undermining our ability to adapt. These self-imposed limitations disrupt our complementary cognitive search capability and may restrict our capacity to find and act upon innovative and creative solutions."

"Complementary cognition should be seen as a starting point in exploring a rich area of human evolution and as a valuable tool in helping to create an adaptive and sustainable society. Our species may owe our spectacular technological and cultural achievements to neurocognitive specialisation and cooperative cognitive search, but our adaptive success so far may belie the importance of attaining an equilibrium of approaches. If this system becomes maladjusted, it can quickly lead to equally spectacular failures to adapt - and to survive, it is critical that this system be explored and understood further."

Credit: 
University of Cambridge

Drug rebates for insurers tied to higher costs for patients, especially the uninsured

Federal agencies that regulate drug pricing and healthcare insurance are concerned that an industry practice of using rebates to lower drug costs for insurers has led to increases in list prices and out-of-pockets costs for patients.

To investigate whether patients with or without insurance were paying more because of rebates to insurers, researchers led by the University of Washington examined cost and price data on more than 400 branded drugs. The study found that rebates were associated with increases in out-of-pocket costs for patients by an average of $6 for those with commercial insurance, $13 for Medicare patients and $39 for the uninsured.

"We know that list prices have been increasing quite dramatically as have rebates, but no one has looked into the association between rebates and out-of-pocket costs," said study lead author Kai Yeung, an affiliate assistant professor at the CHOICE Institute in the UW School of Pharmacy. "Increases in out-of-pocket costs are associated with rebates, however rebates also help keep premium costs down."

Consequently, said Yeung, who is also an assistant professor at Kaiser Permanente Bernard J. Tyson School of Medicine, "There has been inadequate focus on the impact the pricing mechanism has on the uninsured, who are most affected."

For the study published June 14 in JAMA, the researchers used data on 444 branded drugs without generic equivalents from national datasets involving healthcare costs and drug prices from 2007 to 2018 including the federal Medical Expenditure Panel Survey and SSR Health, a private company that collects and analyzes prescription drug pricing data.

Researchers point out that the cost increases can impact patient health, since higher costs can cause patients to take their medication less often. That, in turn, can lead to increased emergency room use and hospitalizations. People in their study who did not have insurance had the poorest health and those with lower incomes were less likely to take medication as prescribed when costs increased.

"Further," the researchers wrote, "uninsured individuals were more likely to be in racial minority groups, amplifying pre-existing disparities in healthcare access."

As a result, the authors suggest future research and policies should focus on decoupling list prices from what patients pay out of pocket, "especially for uninsured individuals."

"The biggest takeaway is understanding that the rebates work to reduce the cost of prescription drugs for insurance companies and may reduce premiums," said co-author Anirban Basu, the Stergachis Family endowed director of the CHOICE Institute and professor of health economics at the UW School of Pharmacy. "And while it's unclear how much the discounts are reducing premiums, they are definitely not translating to lower out-of-pocket costs for the patients who are using the treatment because of this structure of coinsurance and copayments tied to the list price."

Stacie Dusetzina, Vanderbilt University School of Medicine, Nashville, Tenn., is also a co-author. This research was supported in part by grant funding from the Donaghue Foundation's Greater Value Portfolio.

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University of Washington

New Web Tool Fights Antibacterial Resistance

In 1943, two scientists named Max Delbrück and Salvador Luria conducted an experiment to show that bacteria can mutate randomly, independent of external stimulus, such as an antibiotic that threatens a bacterial cells' survival. Today the Luria-Delbrück experiment is widely used in laboratories for a different purpose--scientists use this classic experiment to determine microbial mutation rates. When performing the Luria-Delbrück experiment, scientists need efficient computer algorithms to extract reliable estimates of mutation rates from data, and they also need well-designed software tools to access these sophisticated algorithms.

Through the years, several web tools that allow researchers to more easily input and analyze data on a computer were developed to increase efficiency and efficacy of the Luria-Delbrück experiment. However, no existing web tool allows scientists to access many recently developed algorithms that can extract even more accurate estimates of microbial mutation rates from data.

Qi Zheng, PhD, professor at the Texas A&M University School of Public Health, recently developed a new web tool called webSalvador to fill several gaps left by existing web tools. In the Microbiology Resource Announcements (MRA) Journal, Zheng explains how WebSalvador offers many desirable capabilities that are vital to bacteria mutation research, including more accurate methods for constructing confidence intervals and new methods for comparing mutation rates.

The web tool also eliminates the need for scientists to learn programming and software language, which Zheng described as an "important barrier" to using the Luria-Delbrück experiment to tackle important problems in mutation research, such as the global public health headache of bacterial drug resistance.

"Learning software languages can be challenging and time consuming for most biologists," Zheng said. "With webSalvador, biologists can input data and see results easily."

Increasing the efficiency and efficacy of the Luria-Delbrück experiment is important because it can ultimately help advance mutation research, which is vital to many branches of life sciences. Zheng cites bacterial drug resistance as one of the most important applications of the Luria-Delbrück experiment, and refers to multi-drug resistant tuberculosis as an example in which advanced mutation research is vital. He calls microbial drug resistance a "wide-spread, global health problem."

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Texas A&M University

Quality supervision, coworker support key to child welfare caseworker retention

Instead of looking at the reasons child welfare caseworkers leave their jobs, Oregon State University researchers examined the common factors among workers who stay in the field, and what makes them feel most satisfied in their work.

In their recent study, researchers found that quality supervisory support and strong relationships with coworkers helped caseworkers feel appreciated and understood, while having adequate technology and equipment helped them manage their workload effectively

They hope child welfare agencies can use this information to support caseworkers and reduce the field's high turnover and burnout rates, which in turn will mean better support for children and families.

"Caseworkers have very challenging jobs, but some are satisfied with the work despite its challenges, and they intend to stay," said co-author Kelly Chandler, an assistant professor in OSU's College of Public Health and Human Sciences. "If we want to improve continuity in terms of service to children and families in the community, it's important to not only minimize the job challenges that are inevitable, but also think about which employees are really thriving and what we can learn from them."

Researchers sent a confidential online survey to all social service specialist caseworkers in Oregon's Department of Human Services in 2018 and were able to use the data from 485 respondents, including 222 from Child Protective Services.

The survey posed a series of statements and asked caseworkers to rank how strongly they agreed with them. The statements covered a range of topics, from job satisfaction and intention to remain, to more specific items about job resources, such as: "My supervisor gives me clear feedback on my job performance" and "I have the technology and equipment to do my job well."

For more quantitative points about job demands, researchers examined objective agency records to measure caseload and case severity. They took a unique approach to measure case severity, basing it on the number of substantiated abuse flags in a single client family, up to a total of five per family.

Case severity was the only job demand shown to have a significant negative impact on whether an employee was a "satisfied stayer;" that is, someone who intended to stay at the agency and was satisfied in their job. They compared satisfied stayers with undecided workers and found caseworkers were 8% less likely to be in the satisfied stayer group if they had severe caseloads.

On the flip side, all three job resources studied -- supervisor quality, coworker support and work tools -- were significantly and positively associated with caseworkers feeling satisfied and wanting to stay in their jobs.

Lead author Brianne Kothari, an assistant professor at OSU-Cascades, said that while there are obvious budget and salary factors that affect caseworker retention, this study demonstrates that agencies also need to remember the value of intangible support for their workers.

"It's really about finding how we can support caseworkers to increase their job satisfaction and intention to stay at ODHS," Kothari said. "They want to feel seen and heard. It might be a pat on the back for one person; it might be something else for another person. This study demonstrates the importance of quality supervisor relationships and the need to identify specific supervisory behaviors that benefit employees. It's also important to remember that all workers, including supervisors, need support."

That kind of emotional support, both from coworkers who are "in the trenches" together, and from supervisors who see how hard caseworkers are working, can go a long way toward helping employees feel that they're not alone, Chandler said.

This study aligns with a broader effort at Oregon DHS to transform the workplace culture and employ more trauma-informed approaches to training at all levels, Kothari said. And it opens the door for further collaboration between OSU and the agency, where researchers can work together to dig into the data and help the agency solidify the best evidence-based practices.

"This is part of our effort to figure out how we can better collaborate with state agencies, which I think really falls within the OSU land grant mission," Kothari said. With ODHS, "There are ways we can think about how we as a larger community can be supportive of these workers, who are really there because they want to make a difference in these children's and families' lives."

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Oregon State University

That song is stuck in your head, but it's helping you to remember

"So, no one told you life was going to be this way.
Your job's a joke, you're broke, you're love life's DOA.
It's like you're always stuck in second gear,
When it hasn't been your day, your week, your month, or even your year..."

If you have watched TV since the 1990s, the sitcom theme song, "I'll Be There for You," has likely been stuck in your head at one point or another. New research from UC Davis suggests these experiences are more than a passing nuisance -- they play an important role in helping memories form, not only for the song, but also related life events like hanging out with friends -- or watching other people hang with their friends on the '90s television show, Friends.

"Scientists have known for some time that music evokes autobiographical memories, and that those are among the emotional experiences with music that people cherish most," said Petr Janata, UC Davis professor of psychology and co-author on a new study.

"What hasn't been understood to date is how those memories form in the first place and how they become so durable, such that just hearing a bit of a song can trigger vivid remembering," said Janata.

The paper, "Spontaneous Mental Replay of Music Improves Memory for Incidentally Associated Event Knowledge," was published online in the Journal of Experimental Psychology: General. Co-authors are Janata and Benjamin Kubit, a postdoctoral researcher in cognitive neuroscience, both of the UC Davis Department of Psychology, and Center for Mind and Brain.

This new research offers an initial glimpse into these mechanisms and, somewhat surprisingly, finds that the songs that get stuck in your head help that process of strengthening memories as they first form, the authors said. Thus, this is the first research to link two of the most common phenomena people experience with music -- earworms (having a song stuck in your head) and music-evoked remembering.

For their latest study, the researchers worked with 25 to 31 different people in each of three experiments, over three different days, spaced weeks apart. Subjects first listened to unfamiliar music, and then, a week later, listened to the music again, this time paired with likewise unfamiliar movie clips. In one instance, movies were played without music. The research subjects, all UC Davis undergraduate and graduate students, were subsequently asked to remember as many details as they could from each movie as the music played. They were also quizzed about their recollection of the associated tunes and how often they experienced each of the tunes as an earworm. None of them had formal music training.

The more the tune played, the more accurate the memory

The results: the more often a tune played in a person's head, the more accurate the memory for the tune became and, critically, the more details the person remembered from the specific section of the movie with which the tune was paired.

With only one week between when they saw the movie, and when they were asked to remember as many details from the movie as they could while listening to the movie soundtrack, the effect of repeatedly experiencing a tune from the soundtrack as an earworm resulted in near-perfect retention of the movie details. These people's memories, in fact, were as good as when they had first seen the movie. Additionally, most subjects were able to report what they were typically doing when their earworms occurred, and none of them mentioned the associated movies coming to mind at those times.

"Our paper shows that even if you are playing that song in your mind and not pulling up details of memories explicitly, that is still going to help solidify those memories," Janata said.

"We typically think of earworms as random nuisance beyond our control, but our results show that earworms are a naturally occurring memory process that helps preserve recent experiences in long-term memory," Kubit said.

Future help for memory loss?

The authors said they hope the research, which is ongoing, could eventually lead to the development of nonpharmaceutical, music-based interventions to help people suffering from dementia and other neurological disorders to better remember events, people and daily tasks.

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University of California - Davis

Hollywood stereotypes of female journalists feed a 'vicious cycle' of sexism

When a fictional female journalist appears on screen, chances are she's about to sleep with one of her sources. It's a trope that infuriates actual women in news media -- and it can have real-life consequences, says University of Florida researcher Frank Waddell, Ph.D.

In shows like "House of Cards" and movies like "Thank You for Smoking," female reporters are quick to trade sex for information. Even when sex with sources has nothing to do with ambition -- such as the hookups in "Sharp Objects," "Top Five," "Trainwreck," and the "Gilmore Girls" reboot, to name a few -- it still portrays unethical behavior.

"In the past 20 to 30 years, Hollywood has really latched on to this. It's incredibly consistent," Waddell said.

At the same time, threats to female journalists have increased. A UNESCO study of 901 journalists from 125 countries shows that 73% experienced online harassment. And in a 2019 survey of women and gender non-conforming journalists in the United States and Canada, 70% experienced threats and 85% felt they had become less safe in past five years.

Waddell, an assistant professor in UF's College of Journalism and Communications, wanted to know who believes these sexist portrayals, as research shows we're most affected by media we perceive as realistic. In a study published in Journalism Studies, he was surprised to uncover no difference between men and women or liberals and conservatives, who tend to indicate lower levels of trust in mainstream media. Less surprising: People who already held sexist beliefs about women journalists found the portrayals believable. With repetition, Waddell explains, those views become more entrenched, creating a vicious cycle.

Understanding who falls for skewed portrayals of female journalists is the first step in finding solutions, he says.

"This is a very specific slice of the pie, but it's in the context of a larger conversation about declining trust in media overall," said Waddell, who is part of UF's multidisciplinary Consortium on Trust in Media and Technology.

In his original concept for the experiment, Waddell wanted to contrast reactions to sexist portrayals of women journalists in popular shows and movies with positive ones. He couldn't find any.

"I was actually struggling so badly to find positive examples that I couldn't do that part of the study," he said. ("Spotlight," the chronicle of the Boston Globe's reporting on child sex abuse in the Catholic church, is a rare exception, but Waddell was concerned that the subject matter could have skewed the data.)

Because most people have few, if any, first-hand encounters with reporters, Hollywood can have an outsized influence. Ways to counter that could include increased contact between regular folks and journalists, whether it's through town hall events, expanded social media interaction, or creative approaches to demystifying what goes on inside a newsroom, Waddell said.

"I'm also hoping that Hollywood can do a better job finding ways to dramatize the practice of journalism," he said. "People are treating women in the newsroom differently because they fail to recognize what they're seeing has nothing to do with real life."

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University of Florida

How political bias impacts believing sexual assault victims

New research from Syracuse University Newhouse School of Public Communications reveals a relationship between political biases and attitudes about sexual assault.

Authored by assistant professor Rebecca Ortiz and PhD student Andrea Smith, the article "A social identity threat perspective on why partisans may engage in greater victim blaming and sexual assault myth acceptance in the #MeToo era," was published in the peer-reviewed journal Violence Against Women.

Ortiz and Smith found that the stronger the partisan identity of Republicans and Democrats, the more likely they were to engage in victim blaming attitudes, which was then related to a lesser likelihood to perceive the #MeToo movement as having a positive impact in the United States, possibly as a way of defending their political identities in a time when many political leaders have been accused of sexual assault.

In this cross-sectional study, the researchers sent a survey to Democrats, Republicans and independents and asked them a series of questions related to how strongly they identify with their political party affiliation.

The next series of questions looked at their attitudes about sexual assault and violence against women. These questions explored how likely they were to agree with myths about sexual assault, such as believing that female victims are at least somewhat responsible. The researchers then broke down responses by political identity and gender.

"What we found is that the more Republicans and Democrats strongly identified with their party, the more likely they were to agree, or at least not strongly disagree, with these sexual assault myths and then the less likely they were to perceive the #MeToo movement as having a positive impact," said Ortiz. "As predicted, these sexual assault myth attitudes were significantly higher among Republicans than Democrats and among men than women. We also found that our participants aligned more closely by party than gender, such that Republican women more closely aligned with Republican men and Democratic men with Democratic women."

However, while the Democratic Party has championed the #MeToo movement and women's rights, the researchers' findings indicate that even strongly partisan Democrats may still be willing to, at least somewhat, question a victim's story or believe in sexual assault myths, perhaps especially when a Democratic politician is accused of harassment or assault.

This narrative has played out on both sides of the political spectrum. In 2016, former President Donald Trump was accused by several women of sexual misconduct and harassment. During the campaign, an infamous tape resurfaced of Trump making lewd remarks about women and bragging about sexually harassing women. He still won the election and enjoyed popular support from Republicans. Likewise, while many Democrats called out former President Trump for the numerous sexual assault allegations against him, some Democrats were far less willing to criticize President Biden when a similar accusation was made by a former staffer during the 2020 elections.

"It appears that both Democrats and Republicans have the potential to engage in victim blaming and acceptance of these harmful cultural myths about sexual assault survivors as a means of preserving and defending their political identities, perhaps especially when powerful members and leaders of their political group are accused of these crimes," said Ortiz.

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Syracuse University