Culture

One in ten have long-term effects 8 months following mild COVID-19

image: Researchers Charlotte Thålin and Sebastian Havervall at Danderyd Hospital and Karolinska Institutet.

Image: 
Ludvig Kostyal

Eight months after mild COVID-19, one in ten people still has at least one moderate to severe symptom that is perceived as having a negative impact on their work, social or home life. The most common long-term symptoms are a loss of smell and taste and fatigue. This is according to a study published in the journal JAMA, conducted by researchers at Danderyd Hospital and Karolinska Institutet in Sweden.

Since spring 2020, researchers at Danderyd Hospital and Karolinska Institutet have conducted the so-called COMMUNITY study, with the main purpose of examining immunity after COVID-19. In the first phase of the study in spring 2020, blood samples were collected from 2,149 employees at Danderyd Hospital, of whom about 19 percent had antibodies against SARS-CoV-2. Blood samples have since then been collected every four months, and study participants have responded to questionnaires regarding long-term symptoms and their impact on the quality of life.

In the third follow-up in January 2021, the research team examined self-reported presence of long-term symptoms and their impact on work, social and home life for participants who had had mild COVID-19 at least eight months earlier. This group consisted of 323 healthcare workers (83 percent women, median age 43 years) and was compared with 1,072 healthcare workers (86 percent women, median age 47 years) who did not have COVID-19 throughout the study period.

The results show that 26 percent of those who had COVID-19 previously, compared to 9 percent in the control group, had at least one moderate to severe symptom that lasted more than two months and that 11 percent, compared to 2 percent in the control group, had a minimum of one symptom with negative impact on work, social or home life that lasted at least eight months. The most common long-term symptoms were loss of smell and taste, fatigue, and respiratory problems.

"We investigated the presence of long-term symptoms after mild COVID-19 in a relatively young and healthy group of working individuals, and we found that the predominant long-term symptoms are loss of smell and taste. Fatigue and respiratory problems are also more common among participants who have had COVID-19 but do not occur to the same extent," says Charlotte Thålin, specialist physician, Ph.D. and lead researcher for the COMMUNITY study at Danderyd Hospital and Karolinska Institutet. "However, we do not see an increased prevalence of cognitive symptoms such as brain fatigue, memory and concentration problems or physical disorders such as muscle and joint pain, heart palpitations or long-term fever."

"Despite the fact that the study participants had a mild COVID-19 infection, a relatively large proportion report long-term symptoms with an impact on quality of life. In light of this, we believe that young and healthy individuals, as well as other groups in society, should have great respect for the virus that seems to be able to significantly impair quality of life, even for a long time after the infection," says Sebastian Havervall, deputy chief physician at Danderyd Hospital and PhD student in the project at Karolinska Institutet.

The COMMUNITY study will now continue, with the next follow-up taking place in May when a large proportion of study participants are expected to be vaccinated. In addition to monitoring immunity and the occurrence of re-infection, several projects regarding post- COVID are planned.

"We will, among other things, be studying COVID-19-associated loss of smell and taste more closely, and investigate whether the immune system, including autoimmunity, plays a role in post-COVID," says Charlotte Thålin.

Credit: 
Karolinska Institutet

A protein with a dual role: Both repair and mutation

image: (A) Mfd repair function. 1. An RNA polymerase is blocked by UV damage in DNA. 2. Mfd binds to RNA polymerase and DNA, and moves along the DNA to remove the RNA polymerase from the DNA. 3. By removing RNA polymerase, RNA is released and Mfd continues on its way, recruiting more DNA repair factors.
(B) Mfd mutagenesis function. 1. When an RNA polymerase travels through the DNA to read its inscriptions, it causes the accumulation of left-handed braids (corresponding to overtwisted DNA) ahead of the protein and right-handed braids (corresponding to undertwisted DNA behind the protein. 2. When Mfd interacts with an active RNA polymerase and binds to DNA, the right-handed braids are concentrated in the small area between Mfd and the RNA polymerase, causing the DNA to unwind. RNA can then be inserted into the double helix and form a DNA:RNA hybrid, the R-loop.

Image: 
© Terence Strick

The Mfd protein repairs bacterial DNA, but can also, to scientists' surprise, promote mutation.

Bacterial mutations can lead to antibiotic resistance.

Understanding this second "role" of the Mfd protein opens up opportunities for combating antibiotic resistance, and also the resistance of tumours to anti-cancer drugs and therapies.

Using a specialized protein, all bacteria are capable of rapidly and effectively repairing damage to their DNA from UV. However, this mutation frequency decline (Mfd) protein plays another role and causes mutations. A team involving scientists from CNRS, ENS-PSL and supported by Inserm has demonstrated and described this phenomenon. Better understanding of mutations opens up prospects in the fight against resistance to antibiotics and anti-cancer therapies. This study was published in PNAS on 5 April 2021.

DNA can undergo many degradations, including UV degradation. Just as a landslide on a railway track will prevent a train from passing, the damage generated by UV rays is an obstacle to RNA polymerase, a protein that travels along the length of DNA to read its instructions. RNA polymerase being blocked at any point prevents damage from being repaired. To restore the "track", bacteria possess the Mfd protein that clears the blocked RNA polymerase, and then recruits other proteins to help with the repairs, avoiding mutations.

Biologists from the Institut de Biologie de l'ENS (CNRS/ENS - PSL/INSERM) have just solved the mystery behind a previously lesser-known role of this protein. It is involved in the formation of DNA areas where mutations appear more easily.

The cell machinery involving the Mfd protein normally repairs DNA, but when a bacterium faces certain stressors, such as the presence of an antibiotic, it takes another route: Mfd grips to an active RNA polymerase as it scrolls through DNA, rather than clearing a blocked RNA polymerase. Once bound together, the two proteins unwind the double DNA helix rapidly and on a large scale, forcing it open. The opening of the two DNA strands creates a favourable environment for the formation of particular zones facilitating mutations: R-loops.

R-loops are still poorly understood structures, but they are the source of many mutations: scientists have shown that nearly half of the mutations in bacteria are due to these structures. As antibiotic resistance is born from mutations, this work, which demonstrates the link between Mfd and R-loops, opens up new perspectives in the fight against antibiotic resistance.

The research team also points out that Mfd has equivalents in the various branches of life and that this mutation mechanism is probably universally present. In humans, for example, the protein homologous to Mfd is involved in accelerated ageing and evolution of tumor resistance to chemotherapy. Scientists believe that a mechanism similar to R-loop formation could occur in cancer cells, introducing mutations that can make them resistant to treatment.

Credit: 
CNRS

Family child care home providers with high diet self-efficacy are better equipped to manage stress

audio: For individuals who care for other people's children in their home, building self-efficacy for healthy eating is an important component of health promotion and can buffer the impact of stress on their diet quality.

Image: 
Journal of Nutrition Education and Behavior

Philadelphia, April 7, 2021 - Building family child care home providers' (FCCH) self-efficacy--an individual's belief in their ability to manage their situation--for healthy eating is an important component of health promotion and can buffer the impact of stress on their diet quality, according to a new study in the Journal of Nutrition Education and Behavior, published by Elsevier.

"The FCCH provider is an important source of child care in this country. A lot of families from lower-income environments use the FCCH because of its affordability and location," said Dianne Ward, EdD, of the Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

FCCH providers can experience multiple stressors including work-life balance, lack of social support from other early care and education professionals, and difficulties managing all aspects of both child care and business operations, often with little to no assistance.

To understand the potential determinants of the health of FCCH providers, a group at risk for high stress, poor sleep, and obesity, researchers examined stress levels, sleep quality, and diet self-efficacy of 166 licensed FCCH providers over the age of 18 from central North Carolina.

The study's results showed diet self-efficacy moderating the FCCH provider stress-diet quality relationship. When stress was low, diet quality was similar among individuals across all levels of diet self-efficacy. With higher stress, those with high diet self-efficacy seem to cope with the stress and have a better diet quality. In contrast, those with low diet self-efficacy seem to be negatively affected by stress and have a poorer diet quality.

"As nutrition professionals, we often get caught up in telling people what to eat. We need to remember to facilitate the how to eat. We need to give people the confidence that they can select, consume, and obtain the right food, and that if they do, they can have a healthy diet. The study underscored how important diet self-efficacy really is," noted Dr, Ward.

Credit: 
Elsevier

Poor children are 'failed by system' on road to higher education in lower-income countries

A generation of talented but disadvantaged children are being denied access to higher education because academic success in lower and middle-income countries is continually 'protected by wealth', a study has found.

The research, which used data from around 3,500 young people in Ethiopia, India, Peru and Vietnam, shows that promising but poorer students 'fall away' during their school years, as challenges associated with their socio-economic circumstances gradually erode their potential. Among children who showed similar levels of ability aged 8, for example, the wealthiest were often over 30 percentage points more likely than the least-wealthy to enter all forms of tertiary education: including university, technical colleges, and teacher training.

Even when they focused only on students who complete secondary school with comparable levels of learning, the researchers found that those from wealthier backgrounds were still more likely to progress to higher education. They describe their findings, reported in the British Education Research Journal, as indicative of the 'protective effect' of wealth in relation to academic advantage.

The study was undertaken by the Research in Equitable Access and Learning (REAL) Centre, Faculty of Education, University of Cambridge. Dr Sonia Ilie, its lead author, said: "In many lower-income countries, low socio-economic status is a continual barrier to young people's attainment. What is clear is that these inequalities in higher education access have nothing to do with ability: this is about systems which are consistently failing poorer children."

The data used in the research was from Young Lives, an international childhood poverty study which is tracking two cohorts of young people from Ethiopia, India, Peru and Vietnam. The Cambridge researchers focused on the group born in 1994/5. Young Lives includes information about education and attainment at ages 8, 12, 15, 19 and 22, and importantly therefore includes the many young people in lower-income countries who may enter higher education after age 19.

The researchers started by comparing basic entry rates into higher education among the poorest 25% and wealthiest 25% of participants. The percentage point gap between these quartiles was 45 in both India and Peru, 41 in Vietnam, and 17 in Ethiopia.

They then analysed higher education progression rates among increasingly comparable groups of students. First, they focused on those with similar demographic characteristics (for example, those specifically from urban settings). They then progressively added more information about their education to examine students who were both in school, and achieving certain attainment levels, aged 8, 12 and 15.

The gap between the poorest and richest students' likelihood of enrolling in higher education narrowed steadily as each level of information was factored in. Given the disparity in the 'raw' wealth gap, this indicates that children from poor backgrounds often fail to progress because they drop out, or under-achieve, throughout primary and secondary school.

Crucially, however, a gap still existed between rich and poor even among students who finished secondary school with comparable levels of learning. The size of the remaining gap reflected the complexities of each country's higher education systems, but showed that at the same level of schooling and learning, wealth played this protective effect.

The study also analysed the progress of 'high-promise' children. The researchers identified all children who had achieved a certain level of literacy at age 8, and then used numeracy and maths scores to compare the educational trajectories of the richest and poorest among this group.

Overall, the attainment gap between high-promise children from the top and bottom wealth quartiles widened during school, even though their test scores were similar at age 8. Ultimately, many more high-promise children from the richest quartile entered higher education compared with the poorest: the percentage point gap between the two groups was 39 in Peru, 32 in India and Vietnam, and 15 in Ethiopia.

"Even among children who do well to begin with, poverty clearly becomes an obstacle to progression," Ilie said. "The reverse also applies: if they are wealthy, even children with initially lower levels of learning catch up with their poorest peers. This is what we mean by the protective effect of wealth."

The study says that the first priority in addressing the higher education wealth gap should be targeted investment in primary education for the very poorest. This is already an emerging policy focus in many lower-income countries, where disadvantaged children, even if they go to school, often have poor learning outcomes. The reasons for this, documented in several other studies, include limited educational resources and support at home, and practical difficulties with school attendance.

The findings also indicate, however, that targeted support should continue during secondary education, where wealth-related barriers persist. In addition, the residual wealth gap even among those who finish secondary school highlights a need for initiatives that will reduce the cost of higher education for disadvantaged students.

The study suggests that means-tested grants may be one viable solution, but further evidence is required. It also warns that at present, taxation-based funding for higher education will essentially 'subsidise a socio-economic elite', while tuition fees will further prohibit access for the poorest.

Professor Pauline Rose, Director of the REAL Centre, said: "If we want to equalise opportunities at the point of entry into higher education, we have to intervene early, when the wealth gaps emerge. This study shows that targeted and sustained interventions and funding are needed for the poorest students not only in their earliest years, but throughout their educational careers."

Credit: 
University of Cambridge

Do school-based interventions help improve reading and math in at-risk children?

School-based interventions that target students with, or at risk of, academic difficulties in kindergarten to grade 6 have positive effects on reading and mathematics, according to an article published in Campbell Systematic Reviews.

The review analyzed evidence from 205 studies, 186 of which were randomized controlled trials, to examine the effects of targeted school-based interventions on students' performance on standardized tests in reading and math.

Peer-assisted instruction and small-group instruction by adults were among the most effective interventions. The authors noted that these have substantial potential to boost skills in students experiencing academic difficulties.

"It is exciting to see that there are many interventions with substantial impacts on math and reading skills, especially in these times when many students have not been able to attend school and the number of students who need extra help may be even larger than usual," said lead author Jens Dietrichson, PhD, of VIVE, the Danish Center for Social Science Research. "It is also interesting that there is large variation: far from all interventions have positive effects, and there are substantial and robust differences between the types of interventions. Thus, schools can boost the skills of students with difficulties by implementing targeted interventions, but it matters greatly how they do it."

Credit: 
Wiley

New findings on how diabetes impacts bone health

In addition to causing blood sugar imbalances, type 1 diabetes can contribute to nerve damage and sensory abnormalities--a condition call neuropathy--and has been linked to a higher risk of bone fractures. A new study published in the Journal of Bone and Mineral Research has examined the effects of type 1 diabetes and diabetic neuropathy on the skeleton.

Investigators found that type 1 diabetes and diabetic neuropathy have various impacts on bone structure, but these effects do not fully explain the higher fracture risk in patients with type 1 diabetes.

The results suggest that the increase in the risk of fractures in type 1 diabetes is multifactorial, with both skeletal and non-skeletal features involved.

"It is important to investigate what leads to an increased risk of fractures in type 1 diabetes. Our results suggest that in addition to bone features, balance and muscle strength also play a role," said lead author Tatiane Vilaca, MD, PhD, of the University of Sheffield, in the U.K. "These findings could help improve approaches to fracture prevention."

Credit: 
Wiley

What are the risk factors for experiencing side effects from childhood cancer treatments?

Steroids are essential for treating children with acute lymphoblastic leukemia, a type of cancer of the blood and bone marrow, but they can cause severe side effects such as psychological reactions and sleep problems. An analysis of all relevant studies published to date indicates that there's insufficient high-quality research investigating the risk factors for these side effects.

The analysis, which is published in Psycho-Oncology, included 24 studies. The authors of the analysis noted that overall, there is little evidence regarding risk factors for steroid-induced psychological reactions and sleep problems in children with acute lymphoblastic leukemia, and the quality of evidence is low. However, evidence suggests that the type and dose of steroids are not related to psychological reactions, but may be related to sleep problems. Younger patients seem at risk for behavioral problems and older patients for sleep problems.

"There is a lot to gain in the prevention and treatment of steroid-induced psychological and sleep problems, and recognition comes first," said senior author Raphaële R.L. van Litsenburg, MD, PhD, of the Princess Máxima Center in The Netherlands. "A standardized registration of these side effects and their risk factors is warranted for future studies."

Credit: 
Wiley

How has the COVID-19 pandemic impacted peoples' interactions with nature?

image: The COVID-19 pandemic and the global response to it have changed many of the interactions that humans have with nature, according to a new article published in People and Nature.

Image: 
Dr. Soga

The COVID-19 pandemic and the global response to it have changed many of the interactions that humans have with nature, in both positive and negative ways. A perspective article published in People and Nature considers these changes, discusses the potential long-term consequences, and provides recommendations for further research.

The authors of the article note that the pandemic constitutes a 'global natural experiment' in human-nature interactions that, without seeking to downplay or ignore its tragic consequences, provides a rare opportunity to produce in-depth knowledge about these interactions and to help establish actions that can have positive effects for both humans and nature.

"Although undeniably tragic, the COVID-19 pandemic may offer an invaluable opportunity to explore an appropriate future relationship between people and nature," said lead author Masashi Soga, PhD, of the University of Tokyo.

Credit: 
Wiley

Heavy water tastes sweet

image: Differences between the behavior of the transmembrane part of the human sweet taste receptor in H2O vs D2O base on analysis of three independent microsecond trajectories.

Image: 
Carmelo Tempra / IOCB Prague

Ordinary pure water has no distinct taste, but how about heavy water - does it taste sweet, as anecdotal evidence going back to 1930s may have indicated? And if yes - why, when D2O is chemically practically identical to H2O, of which it is a stable naturally-occurring isotope? These questions arose shortly after heavy water was isolated almost 100 years ago, but they had not been satisfactorily answered until now. Now, researchers Pavel Jungwirth and Phil Mason with students Carmelo Tempra and Victor Cruces Chamorro at the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague), together with the group of Masha Niv at the Hebrew University and Maik Behrens at the Technical University of Munich, found answers to these questions using molecular dynamics simulations, cell-based experiments, mouse models, and human subjects. In their research article published in Communications Biology, they show conclusively that, unlike ordinary water, heavy water tastes sweet to humans but not to mice, with this effect being mediated by the human sweet taste receptor.

Heavy water (D2O) differs from normal water (H2O) by an H-D isotopic substitution only, and as such, should not be chemically distinct. Leaving aside a trivial 10% change in density due to the doubled mass of D compared to H, differences in properties of D2O vs H2O, such as pH or melting and boiling points, are indeed very small. These differences are solely due to nuclear quantum effects, namely, changes in zero-point vibrations, which lead to a slightly stronger hydrogen bonding in D2O than in H2O.

"Despite the fact that the two isotopes are nominally chemically identical, we have shown conclusively that humans can distinguish by taste (which is based on chemical sensing) between H2O and D2O, with the latter having a distinct sweet taste," commented Pavel Jungwirth on the principal result of their study. In their work, the authors complement taste experiments on human subjects with tests on mice and on HEK 293T cells transfected with the human sweet taste receptor TAS1R2/TAS1R3, and with molecular modelling. The results consistently point to the fact that the sweet taste of heavy water is mediated in humans by the TAS1R2/TAS1R3 receptor. Future studies should be able to elucidate the precise sites and mechanisms of action, as well as the reason why D2O activates TAS1R2/TAS1R3 in particular, resulting in a sweet (but not other) taste.

While clearly not a practical sweetener, heavy water provides a glimpse into the wide-open chemical space of sweet molecules. Since heavy water has been used in medical procedures, the finding that it can elicit responses of the sweet taste receptor, which is located not only on the tongue but also in other tissues of the human body, represents an important information for clinicians and their patients. Moreover, due to wide application of D2O in chemical structure determination, chemists will benefit from being aware of the present observations.

Finally, it is worth mentioning that 86 years ago, Science published a short letter by H. C. Urey, Nobelist for the discovery of deuterium (H. C. Urey & G. Failla, Science, 81, 273, 1935. http://doi.org/10.1126/science.81.2098.273-a), stating authoritatively that D2O is undistinguishable from H2O by taste, which had a strong albeit misleading effect on the ongoing discussion about the subject.

"Our study thus resolves an old controversy concerning the sweet taste of heavy water using state-of-the-art experimental and computer modelling approaches, demonstrating that a small nuclear quantum effect can have a pronounced influence on such a basic biological function as taste recognition," concludes Pavel Jungwirth.

Credit: 
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)

South Korea data helps create framework to identify COVID-19 vulnerable areas worldwide

image: TTUHSC's Yoonjung Lee, Pharm.D., Ph.D., joined a group of researchers who developed a framework to identify pockets of COVID-19-vulnerable populations through the use of socioeconomic status and epidemiological determinants.

Image: 
TTUHSC

Though the U.S. and South Korea recorded their first official COVID-19 case on the same day, January 20, 2020, there were notable differences in how each country would ultimately address what has become the world's most severe pandemic since 1918.

Yoonjung Lee, Pharm.D., Ph.D., a pharmacy preceptor and pharmaceutical sciences researcher at the Texas Tech University Health Sciences Center (TTUHSC) Jerry H. Hodge School of Pharmacy, said she was surprised at how South Korea effectively managed the pandemic without the business shutdowns and lockdowns that occurred in China, the U.S. and many European countries.

"I am amazed at how the Korean government had prompt and effective public health interventions to not only address COVID-19, but also to address COVID-19-vulnerable populations simultaneously," Lee said. "That could be why the incidences of COVID-19 cases drastically decreased toward the late phase of our study."

The study Lee referred to is one that she and a group of researchers recently conducted to develop a methodological framework for identifying pockets of COVID-19-vulnerable populations through the use of socioeconomic status (SES) and epidemiological determinants. They then applied data taken from South Korea's response to COVID-19 to operationalize and demonstrate the value of the framework.

Other members of the research team included Principal Investigator David O. Carpenter, M.D., and primary author Bayarmagnai Weinstein, M.D., MPH, from the University of Albany; Alan R da Silva, Ph.D., (University of Brasília); Dimitrios E. Kouzoukas, Ph.D., (Edward Hines, Jr. VA Hospital); Tanima Bose, Ph.D., (Ludwig-Maximilian University of Munich); Gwang-Jin Kim, Ph.D., (University of Freiburg-Germany); Paola A. Correa, Ph.D., (Howard Hughes Medical Institute); Santhi Pondugula, Ph.D., (University of Florida); and Jihoo Kim, M.S., (Hanyang University-Seoul).

Their study, "Precision Mapping of COVID-19 Vulnerable Locales by Epidemiological and Socioeconomic Risk Factors, Developed Using South Korean Data," was published Jan. 12 in the International Journal of Environmental Research and Public Health.

In previous research conducted during and after more recent, and less severe pandemics such as SARS (Severe Acute Respiratory Syndrome), swine flu (H1N1) and MERS (Middle East Respiratory Syndrome), investigators had defined a gap in how these illnesses were detected and treated among differing populations. Those populations considered to be socioeconomically disadvantaged seemed to bear the brunt of the diseases while those populations considered to be more affluent and educated were significantly less affected.

Because of these earlier studies, Lee said the research team believed there was the potential to reduce the outbreak of COVID-19 by utilizing targeted interventions. However, those earlier studies focused solely on socioeconomic handpicked by their investigators. More recent studies also had provided COVID-19 risk factors but none had identified COVID-19-vulnerable locales associated with SES and epidemiological factors specific enough to the virus.

"Indeed, the previous studies used SES variables based on researchers' preferences, irrespective of their COVID-19 relevance. Consequently, the SES measures across these studies were incomparable, limiting their usefulness," she added.

Lee said her group's COVID-19 study identified and used seven specific socioeconomic and epidemiologic factors: health care access, health behavior, crowding, area morbidity, education, difficulty to social distancing and population mobility.

To ensure they captured information about the study population's socioeconomic and population health that was as complete as possible, Lee said the team applied Coleman's Foundations of Social Theory, which combines the observed social actions of individuals with the rational concept of economists that contends individuals acts independently of one another and for their own self-interest.

"Coleman's Social Theory guided us to collect data in each of three fundamental domains -- material, human and social capitals -- that concertedly characterize each geographic unit's SES and area-health status in the study," Lee explained.

Lee said the team further filtered the study's variables by utilizing Blumenshine's conceptual mechanistic framework, which describes the potential causes of disparities in the U.S. during an influenza or respiratory infection pandemic. It attributes those disparities to varying levels of exposure to the virus, differences in susceptibility to the disease and distinct variations in access to health care.

"That directed us to causally relevant variables to COVID-19, as they determine the likelihood of being exposed to the virus agent, of contracting the disease upon exposure and of receiving timely and effective treatment after the disease has developed," Lee said.

Integrating Coleman's Foundations of Social Theory and Blumenshine's mechanistic framework helped the research team formulate a universal SES definition and select SES indicators that were mechanistically and casually relevant to COVID-19 health outcomes. The development of this methodological framework made this research unique because it allowed the team to identify COVID-19-vulnerable locales through their associated SES and epidemiological determinants.

"Through this approach, we could have universal SES variables with acceptable generalizability and methodological capacity," Lee said. "Consequently, this helped make our study's regression model stronger and more accurate by using SES variables that were relevant to COVID-19."

Lee said the significance of the research is that it provides a methodological framework and precision mapping method that is globally replicable for COVID-19 and future pandemics because it provides robust SES measurements based on the established theories for reducing bias from arbitrary data selections. In fact, she contended, the novelty of the work speaks to the integrity of the study's design and the statistical methodology of the research.

"Firstly, the combined use of global and spatial statistical methods increased the accuracy as global models verified the geographical model," Lee said. "Secondly, we collaborated in this study with Alan da Silva, who developed the negative binomial extension of the geographically weighted regression. His application of this method eliminated the tool's erroneous use while also optimizing the model to study the data. Lastly, our study showed the progression of the COVID-19 epidemic over three consecutive time-periods, which was a novel approach at the time of the study."

In using the South Korea data, the study showed the risk of COVID-19 increased with higher area morbidity, risky health behaviors, crowding and population mobility. Other factors that influenced risk included education, lower social distancing and the ability to access health. Yet, Lee said, falling COVID-19 risks and spatial shifts over three consecutive time periods (early-phase, middle-phase and late-phase) reflected effective public health interventions in South Korea.

"This finding can be different if other data is used, though the South Korean data, based on our knowledge, was the most detailed and publicly available data with open access, which was the reason why we used South Korean data in our study," Lee said. "Therefore, as depicted in our study, it is crucial to identify COVID-19-vulnerable locales associated with SES and COVID-19 specific epidemiological factors and then to target prompt and effective public health interventions toward these locales for effective pandemic control."

Credit: 
Texas Tech University Health Sciences Center

The incredible bacterial 'homing missiles' that scientists want to harness

image: An illustration of tailocins, and their altruistic action painted by author Vivek Mutalik's daughter, Antara.

Image: 
Antara Mutalik

Imagine there are arrows that are lethal when fired on your enemies yet harmless if they fall on your friends. It's easy to see how these would be an amazing advantage in warfare, if they were real. However, something just like these arrows does indeed exist, and they are used in warfare ... just on a different scale.

These weapons are called tailocins, and the reality is almost stranger than fiction.

"Tailocins are extremely strong protein nanomachines made by bacteria," explained Vivek Mutalik, a research scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) who studies tailocins and phages, the bacteria-infecting viruses that tailocins appear to be remnants of. "They look like phages but they don't have the capsid, which is the 'head' of the phage that contains the viral DNA and replication machinery. So, they're like a spring-powered needle that goes and sits on the target cell, then appears to poke all the way through the cell membrane making a hole to the cytoplasm, so the cell loses its ions and contents and collapses."

A wide variety of bacteria are capable of producing tailocins, and seem to do so under stress conditions. Because the tailocins are only lethal to specific strains - so specific, in fact, that they have earned the nickname "bacterial homing missiles" - tailocins appear to be a tool used by bacteria to compete with their rivals. Due to their similarity with phages, scientists believe that the tailocins are produced by DNA that was originally inserted into bacterial genomes during viral infections (viruses give their hosts instructions to make more of themselves), and over evolutionary time, the bacteria discarded the parts of the phage DNA that weren't beneficial but kept the parts that could be co-opted for their own benefit.

But, unlike most abilities that are selected through evolution, tailocins do not save the individual. According to Mutalik, bacteria are killed if they produce tailocins, just as they would be if they were infected by true phage virus, because the pointed nanomachines erupt through the membrane to exit the producing cell much like replicated viral particles. But once released, the tailocins only target certain strains, sparing the other cells of the host lineage.

"They benefit kin but the individual is sacrificed, which is a type of altruistic behavior. But we don't yet understand how this phenomenon happens in nature," said Mutalik. Scientists also don't know precisely how the stabbing needle plunger of the tailocin functions.

These topics, and tailocins as a whole, are an area of hot research due to the many possible applications. Mutalik and his colleagues in Berkeley Lab's Biosciences Area along with collaborators at UC Berkeley are interested in harnessing tailocins to better study microbiomes. Other groups are keen to use tailocins as an alternative to traditional antibiotics -which indiscriminately wipe out beneficial strains alongside the bad and are increasingly ineffective due to the evolution of drug-resistance traits.

In their most recent paper, the collaborative Berkeley team explored the genetic basis and physical mechanisms governing how tailocins attack specific strains, and looked at genetic similarities and differences between tailocin producers and their target strains.

After examining 12 strains of soil bacteria known to use tailocins, the biologists found evidence that differences in the lipopolysaccharides - fat- and sugar-based molecules - attached to the outer membranes could determine whether or not a strain is targeted by a particular tailocin.

"The bacteria we studied live in a challenging, resource-poor environment, so we're interested to see how they might be using tailocins to fight for survival," said Adam Arkin, co-lead author and a senior faculty scientist in the Biosciences Area and technical co-manager of the Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA) Scientific Focus Area. Arkin noted that although scientists can easily induce bacteria to produce tailocins in the lab (and can easily insert the genes into culturable strains for mass production, which will be handy if we want to make tailocins into medicines) there are still a lot of unanswered questions about how bacteria deploy tailocins in their natural environment, as well as how - and why - particular strains are targeted with an assassin's precision.

"Once we understand the targeting mechanisms, we can start using these tailocins ourselves," Arkin added. "The potential for medicine is obviously huge, but it would also be incredible for the kind of science we do, which is studying how environmental microbes interact and the roles of these interactions in important ecological processes, like carbon sequestration and nitrogen processing."

Currently, it's very difficult to figure out what each microbe in a community is doing, as scientists can't easily add and subtract strains and observe the outcome. With properly harnessed tailocins, these experiments could be done easily.

Mutalik, Arkin, and their colleagues are also conducting follow-up studies aiming to reveal tailocins' mechanisms of action. They plan to use the advanced imaging facilities at Berkeley Lab to take atomic-level snapshots of the entire process, from the moment the tailocin binds to the target cell all the way to cell deflation. Essentially, they'll be filming frames of a microscopic slasher movie.

Credit: 
DOE/Lawrence Berkeley National Laboratory

AI-powered symptom checkers can help healthcare systems deal with the COVID-19 burden

AI-powered symptom checkers can potentially reduce the number of people going to in-person clinics during the pandemic, but first, researchers say, people need to know they exist.

COVID symptom checkers are digital self-assessment tools that use AI to help users identify their level of COVID-19 risk and assess whether they need to seek urgent care based on their reported symptoms. These tools also aim to provide reassurance to people who are experiencing symptoms that are not COVID-19 related.

Most platforms, like Babylon and Isabel, are public-facing tools, but the University of California, San Francisco (UCSF) has one of the first COVID-19 symptom checkers that is fully integrated with the users' medical records, allowing for immediate appointment scheduling.

A mixed-methods study at the University of Waterloo found that 18- to 34-year-old young adults, typically the first age group to adopt new technologies, were unaware of the existence of these platforms.

"Young adults are usually eager adopters of technology, so we were a little surprised by this finding," said lead researcher Stephanie Aboueid, a PhD candidate in the School of Public Health and Health Systems. "Symptom checkers have the potential to reduce the burden on health-care systems and the risk of person-to-person infection, so we wanted to find out how to improve these platforms so more people use them."

Of the 22 university students interviewed in winter and spring of 2020, nine of them did not know the tools exist. The researchers also conducted a survey on general symptom checkers in winter 2021, and data suggested 88 per cent (1,365 out of 1,545) of participants did not use one in the past year.

Findings from the smaller qualitative study suggest that three-quarters of those who had used government-issued symptom checkers were satisfied with them. Those who used non-government symptom checkers found the experience suboptimal, citing a lack of trust and credibility.

"One of the findings was that users wanted more personalization and were less trusting of tools that gave the same results to everyone," Aboueid said. "The UCSF system was able to reduce the number of visits while taking into account underlying conditions along with the symptom checks and booking follow-up appointments when needed."

Besides more personalization, the researchers found that other improvements to existing symptom checkers include providing users more information about the creators of the platform, providing more explanation of the symptoms in lay language, more language options and the option to get tested at a nearby location.

Credit: 
University of Waterloo

Characteristics of multisystem inflammatory syndrome in children during COVID-19

What The Study Did: The clinical and other characteristics of multisystem inflammatory syndrome in children in the United States, a condition that occurs in association with the COVID-19 pandemic, are described in this study.

Authors: Ermias D. Belay, M.D., of the Centers for Disease Control and Prevention in Atlanta, is the corresponding author.

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

(doi:10.1001/jamapediatrics.2021.0630)

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

Credit: 
JAMA Network

Gut microbiome plays role in autism

Washington, D.C. - April 6, 2021 - A new study has demonstrated that autism spectrum disorder is related to changes in the gut microbiome. The findings are published this week in mSystems, an open-access journal of the American Society for Microbiology.

"Longitudinally, we were able to see that within an individual, changes in the microbiome were associated with changes in behavior," said principal study investigator Catherine Lozupone, PhD, a microbiologist in the Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado. "If we are going to understand the link between the gut microbiome and autism, we need more collaborative efforts across different regions and centers to get really thorough generalizable information about this relationship."

In the new study, researchers compared the gut microbiome composition between individuals with autism spectrum disorder and neurotypical controls in Arizona and Colorado using standardized DNA extraction and sequencing methods. The researchers found that the gut microbiome composition differed between individuals in Arizona and those in Colorado and gastrointestinal symptoms were significantly higher in those with autism compared with those without autism in Arizona but not Colorado. Gut microbiome composition was significantly associated with autism while controlling for study-site location but not when controlling for gastrointestinal symptoms.

The researchers also longitudinally evaluated the gut microbiome's relationship to autism behavioral severity, diet, and gastrointestinal symptoms in the individuals from Colorado. "We reached out to study participants every three months or so and had them fill out a number of checklists, one being the aberrant behavior checklist which looks at behaviors that are associated like inappropriate speech and repetitive motions," said Dr. Lozupone. "A food frequency questionnaire asked participants what they were eating in the past week. We also asked what types of GI symptoms participants were experiencing. We obtained fecal samples to look at the microbiome. We collected all this data to see how it related to each other."

In the longitudinal analysis, the researchers found that difference in levels of lethargy/social withdrawal measured in individuals at different time points correlated with the degree of change in gut microbiome composition and that a worsening of inappropriate speech between time points was associated with decreased gut microbiome diversity.

"We need more research, but our work shows that the gut microbiome is playing a role in the provocation of symptoms in kids with autism spectrum disorder," said Dr. Lozupone.

"This further supports the fact that the gut microbiome could be a valuable therapeutic target for children with autism spectrum disorders. I know that some labs have been exploring things like fecal microbiome transplant in these children and having some promising results."

Further work to tease out the mechanisms at play could lead to new therapies for children with autism.

Credit: 
American Society for Microbiology

Young people with autism improved their communication with their families during lockdown

The period with the strictest lockdown conditions and quarantining posed additional problems for young people with autism spectrum disorder (ASD) and their families, given that their routines were suddenly disrupted. Routines form an essential aspect of their everyday life and life structure. However, their response and adaptation to this new situation was better than expected in aspects like communication and interaction with their families.

A study conducted by researchers from the Universitat Oberta de Catalunya, the University of Perugia and the ABAULA Occupational Therapy and Child and Adolescent Psychology Centre in Girona studied the behaviour of young people who suffer autism spectrum disorder during the strictest lockdown period (March, April, May and June 2020) to lay the foundations for future support more in line with their actual needs.

According to the authors of the study, most of the families that participated in the study observed a change in the emotional state of their child with ASD. Specifically, parents stressed that during lockdown their children were happier, calmer and more placid than they were before it. To a great extent, they benefitted from the increase in the amount of time they spent with their families and the routines they adopted.

"Families stressed that children and adolescents with ASD adapted to the situation much better than they expected. In fact, following an initial period of complexity, they improved in aspects such as communication, relationships and emotional responses and they even participated more often in routines proposed by their families", highlighted Cristina Mumbardó Adam, an affiliated member of the UOC's Cognition and Language Research Group (GRECIL), a Disability and Quality of Life: Educational Aspects (DISQUAVI) researcher and the lead author of this study.

In this sense, the authors relate that, in the European context, normal working hours do not necessarily make it easy for families to spend more quality time with their children, given that long working days make it hard to strike a work-life balance. However, the timetable flexibility brought in with the pandemic has provided families with more time to look after, grow with, teach and make progress with their children.

Care and technological support

In spite of these results, families with these children in their care also stressed that they suffered greater difficulties at the start of the quarantine. This was not just due to the disruption of their habits, but also because their care and educational resources were not prepared for this new situation.

"Families lamented the lack of support from their schools, which, like all schools, had to reorganize, which took some time to achieve. However, families did highly appreciate having more time to spend with their children, to get to know them better and be able to broaden their range of interests", highlighted Mumbardó. The expert also stated that education centres and professionals "did everything they could during the quarantine to reach all their students" although the situation has shown that "it is clear that new measures are necessary to face such challenges."

Moreover, the experts also assessed the adaptation and response of youth with ASD to processes they were less familiar with, such as the use of new technologies to stay in contact, especially video calls.

They found that these youngsters also respond well to new remote communication channels. For example, seeing their family members, teachers and friends on video calls made during lockdown increased their well-being and calmness.

"Technology was of great help and although sometimes they did not know how to use these new means of communicating with someone, just being able to see a grandparent, classmates and other family members made them happier and calmer", said the researcher.

However, the authors point out that due to the variability of symptoms associated with ASD, the results are applicable to these families, but not necessarily to other family units.

Lack of social understanding

Additionally, the quarantine and lockdown situation also highlighted the lack of social understanding suffered by people with autism spectrum disorder and their families. This situation was especially evident at the specific times during the pandemic when the social groups with the greatest difficulties were allowed to go outside.

In this context, some families were rebuked by their neighbours for apparently not respecting the lockdown and they were unwilling to stigmatize their children by making them wear items like blue scarves as a means of identification. "This unpleasant situation was experienced by a lot of people who had the right to go outside because they needed to and it was very hard on many families", stated Mumbardó.

Finally, the experts explained that future research in this area must focus on benefits and the development of policies to ensure the well-being and academic performance of children with ASD who attend inclusive schools.

"Policymakers and stakeholders should take this study into account in any future decision-making processes related to the Covid-19 pandemic", concluded the authors.

Credit: 
Universitat Oberta de Catalunya (UOC)