Culture

New research presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, held online) shows that a shorter time from symptom onset to hospitalisation is associated with more serious disease and death in patients with COVID-19. The study is by Dr Annie Wong-Beringer and colleagues, University of Southern California (USC) School of Pharmacy, Los Angeles, CA, USA, and presented at ECCVID by co-author Amanda Chron.

Patients with COVID-19 assessed in this study presented to the Huntington Memorial Hospital, Pasadena, CA, USA, for care after varying duration of symptom onset. In this study, the authors evaluated patient characteristics and the relationship between the timeline of symptoms prior to hospitalisation and the resultant outcomes.

All patients who were hospitalised from home due to COVID-19 between March 14, 2020 to May 14, 2020 with a positive PCR result for SARS-CoV-2 were evaluated via retrospective review of electronic medical records to obtain pertinent demographic, laboratory, and clinical information. Patients were grouped based on the time from onset of symptoms to hospitalisation and compared for clinical characteristics, treatment, and outcomes.

The study included 252 patients; 33% presented within 3 days while 27% were after 1 week from onset of symptoms. Patients presenting shortly (within 3 days) after symptom onset tended to be older (65 vs 58 years) and were more likely to have hypertension (59% vs 41%) and chronic kidney disease (14% vs 3%) than those admitted after one week.

However, this group that presented within 3 days also presented with fewer symptoms overall such as fever (55% vs 66%), shortness of breath (48% vs 66%), non-productive cough (40% vs 66%,) and muscle/joint pain (12% vs 26%) but had higher levels of organ failure and a worse overall assessment based on a severity score called APACHE II, which factors in physiology, age and chronic conditions. This quicker-presenting group also ultimately were more likely to develop acute respiratory distress syndrome (13% vs 6%) and have higher mortality (15% vs 3%) than those presenting at hospital more than one week after symptom onset.

Further analysis of the study groups revealed that just over half of the patients (55%) received antiviral therapy, and it was more likely to be given to those who presented with fever with shortness of breath and/or septic shock. Despite receipt of antiviral therapy, mortality rate remained high at 23% in those presenting within 3 days compared to 5% in those presenting after one week. By comparison, among those who did not receive antiviral therapy, mortality was 7% in the quicker-presenting group whereas none died in the group presenting after 7 days.

The authors conclude: "Our findings suggest that patients with COVID-19 who had significant comorbidities became acutely ill with severe presentation shortly (within 3 days) following onset of symptoms and were at significant risk for complications and death despite receipt of antiviral therapy. Aggressive management and vaccine prioritisation should be directed at this patient population."

A contact tracing study presented at this year's ESCMID Conference on Coronavirus Disease (ECCVID) confirms the effectiveness of wearing of masks in public, handwashing, and social distancing to protect against SARS-CoV-2 infection. The study is by Assistant Professor Direk Limmathurotsakul, Mahidol University, Bangkok, Thailand, and Centre for Tropical Medicine and Global Health, University of Oxford, UK, and colleagues from the Thai Ministry of Public Health.

Evaluation of the effectiveness of mask-wearing by healthy people in the general public against SARS-CoV-2 infection is urgently needed. Given the current lack of evidence, the authors sought to evaluate the effectiveness of mask-wearing, handwashing, social distancing, and other protective measures against SARS-CoV-2 infection in public in Thailand.

They conducted a case-control study with 211 cases and 839 non-matched controls using all contact tracing records of Thailand's national Surveillance and Rapid Response Team. This study included contact investigations of three large clusters of COVID-19 identified in nightclubs, boxing stadiums, and a state enterprise office in Thailand.

Cases were asymptomatic contacts of COVID-19 patients identified between 1 and 31 March 2020 who were diagnosed with COVID-19 by 21 April 2020; controls were asymptomatic contacts who were not diagnosed with COVID-19. Participants were asked about practices during contact periods with a case. Adjusted odds ratios were estimated for associations between protective measures and diagnosis of COVID-19 using statistical modelling.

The researchers found that wearing masks all the time during contact was independently associated with a 77% lower risk of COVID-19 infection compared to not wearing masks. However, only wearing masks sometimes during contact was not associated with reduced risk of infection. The type of mask worn was not independently associated with infection. Those who wore masks all the time also were more likely to practice social distancing.

Maintaining at least a 1 metre distance from the COVID-19 patient reduced the risk of infection by 85%, while restricting close contact with a case to less than 15 minutes reduced the risk of being infected by 76% compared with contact of more than 15 minutes. Frequent handwashing also reduced the risk of infection by 66%.

The authors conclude: "Our findings support consistent wearing of masks, handwashing, and social distancing in public to protect against COVID-19 infection."

Criticisms of COVID-19 models by Democratic elites in May 2020 appeared to undermine public support for the models' use - and trust in science more broadly - according to a series of survey experiments conducted with the participation of more than 6,000 Americans. However, whether Republican elites criticized or supported the models appeared to have little effect. Sarah Kreps and Douglas Kriner suggest the lack of response to Republican messaging could be due to the party's split messaging on science-backed guidance for this issue. When Democrats criticized COVID-19 models, however, it strongly contradicted the public's expectations. "The fact is that whether or not political leaders' science communication sways people, they have an ethical obligation to treat the science with care, acknowledging uncertainty while asserting that we are constantly updating with new understandings and data about the virus," says Kreps, the co-author of the study. Since models are built on abstractions and incomplete data that make them inherently uncertain, and research on the novel coronavirus is still in its infancy, models predicting the virus' spread have sometimes been inaccurate. It has remained unclear how competing communications about uncertainty in COVID-19 models affects public support for and trust in science. To better understand the effects of science communications in the context of the pandemic, Kreps and Kriner developed five survey experiments and used them to assess shifting public attitudes toward references to COVID-19 models from prominent Democrats and Republicans. The surveys were designed to test responses to both the cue giver (the Democrat or Republican) and to whether his or her statement ignored, acknowledged, highlighted, or weaponized model uncertainty. Based on their findings, Kreps suggests scientists should avoid emphasizing dire implications associated with epidemiological models while sidestepping uncertainty altogether, since this approach could backfire if projections prove incorrect. "Instead, they should acknowledge that models are simplifications of reality and our best estimate based on a lot of moving parts," she says. "Politicians can help convey to the public what we know and what we still don't know about the virus, and stress the need to adapt policies in response to new information," Kriner adds.

MADISON, Wis. -- The mature brain is infamously bad at repairing itself following damage like that caused by trauma or strokes, or from degenerative diseases like Parkinson's. Stem cells, which are endlessly adaptable, have offered the promise of better neural repair. But the brain's precisely tuned complexity has stymied the development of clinical treatments.

In a new study addressing these hurdles, University of Wisconsin-Madison researchers demonstrated a proof-of-concept stem cell treatment in a mouse model of Parkinson's disease. They found that neurons derived from stem cells can integrate well into the correct regions of the brain, connect with native neurons and restore motor functions.

The key is identity. By carefully tracking the fate of transplanted stem cells, the scientists found that the cells' identity -- dopamine-producing cells in the case of Parkinson's -- defined the connections they made and how they functioned.

Coupled with an increasing array of methods to produce dozens of unique neurons from stem cells, the scientists say this work suggests neural stem cell therapy is a realistic goal. However, much more research is needed to translate findings from mice to people.

The team, led by UW-Madison neuroscientist Su-Chun Zhang, published its findings Sept. 22 in the journal Cell Stem Cell. The research was led by Zhang lab postdoctoral researchers Yuejun Chen, Man Xiong and Yezheng Tao, who now hold faculty positions in China and Singapore.

"Our brain is wired in such an accurate way by very specialized nerve cells in particular locations so we can engage in all our complex behaviors. This all depends on circuits that are wired by specific cell types," says Zhang, a professor of neuroscience and neurology at UW-Madison's Waisman Center. "Neurological injuries usually affect specific brain regions or specific cell types, disrupting circuits. In order to treat those diseases, we have to restore these circuits."

To repair those circuits in the Parkinson's disease mouse model, the researchers began by coaxing human embryonic stem cells to differentiate into dopamine-producing neurons, the kind of cells that die in Parkinson's. They transplanted these new neurons into the midbrains of mice, the brain region most affected by Parkinson's degeneration.

Several months later, after the new neurons had time to integrate into the brain, the mice showed improved motor skills. Looking closely, Zhang's group was able to see that the transplanted neurons grew long distances to connect to motor-control regions of the brain. The nerve cells also established connections with regulatory regions of the brain that fed into the new neurons and prevented them from being overstimulated.

Both sets of connections -- feeding in and out of the transplanted neurons -- resembled the circuitry established by native neurons. This was only true for dopamine-producing cells. Similar experiments with cells producing the neurotransmitter glutamate, which is not involved in Parkinson's disease, did not repair motor circuits, revealing the importance of neuron identity in repairing damage.

To finally confirm that the transplanted neurons had repaired the Parkinson's-damaged circuits, the researchers inserted genetic on-and-off switches into the stem cells. These switches turn the cells' activity up or down when they are exposed to specialized designer drugs in the diet or through an injection.

When the stem cells were shut down, the mice's motor improvements vanished, suggesting the stem cells were essential for restoring Parkinson's-damaged brains. It also showed that this genetic switch technology could be used to fine-tune the activity of transplanted cells to optimize treatment.

The Zhang group and other researchers have spent years developing methods to turn stem cells into the many different types of neurons within the brain. Each neurological disease or injury would require its own specialized nerve cells to treat, but the treatment plans would likely be broadly similar. "We used Parkinson's as a model, but the principle is the same for many different neurological disorders," says Zhang.

The work has personal meaning to Zhang. As a physician and scientist, he often receives letters from families desperate for help treating neurological disorders or brain trauma. It's also an experience he can relate to. Six years ago, Zhang was in a bike accident and broke his neck. When he awoke partially paralyzed in the hospital, his first thought was of how stem cells -- which he had already researched for years -- could help him recover.

Now, largely rehabilitated after years of physical therapy, Zhang still believes that the right stem cell treatments could, in the future, help people like him and the families he hears from.

To that end, Zhang's group is currently testing similar treatments in primates, a step toward human trials.

"There is hope, but we need to take things one step at a time," he says.

One of the important objectives of green chemistry is the use of eco-friendly solvents and catalysts to perform chemical reactions. Catalysts such as organocatalysts, enzymes, and ionic liquids have shown very assuring results in synthesis by reducing the number of hazardous effects of chemical reactions. Among those catalysts, the activities of ascorbic acid are promising because of its extraordinary abilities.

Ascorbic acid (Vitamin C or ascorbate) is the most well-known vitamin found in different types of foods, most commonly in fruits. For many years, ascorbic acid has been used as a constituent of various dermatologic drugs and cosmetics. However, because of the lack of an enzyme called gulonolactone oxidase, humans and apes cannot synthesize ascorbic acid. Ascorbic acid was first isolated in 1928 by Hungarian biochemist Albert Szent-Györgyi and he named it as hexuronic acid. In 1932, Haworth and King independently established the molecular structure of hexuronic acid and renamed it as ascorbic acid.

Ascorbic acid is an antioxidant. Its oxidation-reduction potential and the stability of its oxidation products contribute values to the application of ascorbic acid as an antioxidant. In addition, as a water-soluble reducing agent and donor antioxidant, ascorbic acid can undergo three consecutive or active types: ascorbate (reduced form), dehydroascorbic acid (oxidized form) and ascorbate radical (intermediate oxidized form). The two-way reactions among these three forms occur very simply due to the low one-electron transfer potential. As a consequence, ascorbic acid has been accepted as a chemically unstable substnace. It is observed that ascorbic acid promptly undergoes pH-dependent autoxidation and makes hydrogen peroxide. In the presence of catalytic metals, this oxidation is accelerated. The combination of metal and ascorbic acid is a very efficient oxidizing system. This system is mainly employed for the hydroxylation of alkenes, aromatics, and other oxidation reactions. Besides, in the presence of catalytic metal ions, ascorbic acid can exert pro-oxidant effects. Ascorbic acid serves as a reducing cofactor for many enzymes.

In organic synthesis, ascorbic acid can be used as a reactant in the preparation of chiral synthons and also as a catalyst to accelerate the reaction. Several important reactions are performed with ascorbic acid: These include the oxidation of amines to carbonyl compounds, cross-coupling of disulfides with aryl iodides, ATRA of polyhalogenated compounds to alkenes, ATRP of polyhalogenated compounds to alkenes, ATRC of polychloroamides to cyclic amides, Amination of aryl halides to primary aromatic amines, oxidation of sulfides, arylation of arenes with anilines, cyclization of aryl radicals with arenes, metal-free synthesis of aryl sulfides, oxidative arylation of vinyl arenes to 2-aryl acetophenones, photoreductive removal of O-benzyl groups, photocatalytic reductive fluoroalkylation of nitrones, reduction of N-heterocyclic nitroaryls to anilines, synthesis of cyclic carbonates from CO2, dehalogenation of vicinal dibromo-, α-halo-, and α,α-dibromocarbonyl compounds, synthesis of quinolinones, aminocoumarins and anilines, solvent-free synthesis of polyhydroquinoline and acridine derivatives, benzylic C-H oxidation, synthesis of benzimidazoles, synthesis of triazoles, synthesis of α-acyloxy carboxamides, synthesis of 2-arylbutanoates, synthesis of benzodiazepines, synthesis of benzoxazepines, synthesis of dihydropyrimidinones, and synthesis of xanthenes. These examples are described in a review published in the journal, Current Organocatalysis. The examples included in this review demonstrate that ascorbic acid is a versatile catalyst for the synthesis of diverse organic compounds. Reactions catalyzed by ascorbic acid are performed in organic or aqueous media.

Ascorbic acid-catalyzed reactions follow diverse mechanistic pathways. The mechanism of most of the processes is proposed by the authors. The multiple functions of ascorbic acid are realized from the suggested mechanisms.

In view of the current situation of conducting organic reactions under environmentally benign circumstances, ascorbic acid-catalyzed mechanistically unique transformations are highly valuable. Based on this study, review, the authors anticipate that additional reactions will be discovered and investigated using ascorbic acid as a catalyst.

SAN ANTONIO - A new study implicates 160 genes in brain shrinkage seen on MRIs of 45,000 healthy adults. The shrinkage is in the cortex, the dimply outer layer of the brain that gives rise to thinking, awareness and action, and largely consists of gray matter.

The study, published Sept. 22 in the journal Nature Communications, examined 34 regions of the cortex in a discovery group of 22,894 individuals, then confirmed the findings in a replication group of 22,635 individuals.

“It is important to understand the biology of multiple regions of the cortex because each is affected differently in the various types of neurodegeneration including Alzheimer’s disease,” said Sudha Seshadri, MD, senior study author from The University of Texas Health Science Center at San Antonio (UT Health San Antonio).

“We asked, ‘What are the genes that seem to determine the thickness, area and volume of gray matter in these regions?’” Dr. Seshadri, who directs the university’s Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, added. “And the genes we found point to interesting pathways that seem to be involved in brain development, vascular and neurodegenerative disease, and some psychiatric conditions.”

Brain shrinkage occurs with normal aging, but the pattern of shrinkage in healthy individuals differs from the pattern in those who develop disease. The genes represent new targets of study for development of drugs to intervene before the onset of clinical symptoms, Dr. Seshadri said.

“This is a very rich resource, and it will be mined for many years to understand the different associations we are seeing,” Dr. Seshadri said. “We are excited to share it with the world.”

Large study samples

Claudia Satizabal, PhD, of the Biggs Institute and Department of Population Health Sciences in UT Health San Antonio’s Joe R. and Teresa Lozano Long School of Medicine, is one of the lead epidemiologists for the research. “This study has considerable statistical power,” Dr. Satizabal said. “Because the results from the first sample were replicated in a second equally large sample, it is less likely that the results are purely due to chance.”

Dr. Satizabal and Dr. Seshadri previously published a study on the volumes of structures deep within the brain that determine subconscious needs such as appetite and sleep. In this new paper the team examined the brain surface, which is important for conscious thinking abilities.

The discovery sample is from 20 study populations within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. The replication sample is from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.

Study limitations included the variability of instruments to image the brain among cohorts due to different scanners, field strengths and analysis software. The sample is composed mainly of European ancestry.

“We seek to add other ethnicities to the CHARGE cohorts, including our Hispanic population of South Texas,” Dr. Seshadri said.

LONDON, ONTARIO - For patients with kidney stones, ureteral stents (hollow devices placed in the ureter - the tube between the kidney and bladder) can be used temporarily to relieve urinary obstruction. Despite the use of antibiotics, ureteral stents often become encrusted with minerals and coated with bacteria. This can lead to complications like infection and the need for replacement surgery.

Published today in Cell Reports Medicine, researchers at Lawson Health Research Institute and Western University conducted a novel microbiome study to examine bacteria associated with ureteral stents. They found that nearly all the stents, whether visibly coated or not, had unique bacterial profiles that were most associated with a patient's medical condition rather than antibiotic use. For patients with ureteral stents, they may benefit from a personalized approach to care and antibiotic treatment.

The study included 241 patients from St. Joseph's Health Care London. The research team collected and analyzed patient urine samples and ureteral stents following surgical removal, as well as relevant patient information such as antibiotic use and history of infections.

"We wanted to know which bacteria were present and whether the bacteria found in urine samples corresponded to the bacteria found on a patient's stent," explains Dr. Kait Al, Postdoctoral Fellow at Lawson and at Western's Schulich School of Medicine & Dentistry. "We found that there was a bacterial community present on almost all stents, even if they were not visibly affected, and that it differed from the bacterial community found in a patient's urine."

These findings challenge long-held beliefs that the urinary tract is a sterile environment devoid of bacteria.

The study revealed that the bacteria present were determined by an individual patient's medical condition. They differed significantly based on comorbidities like irritable bowel syndrome, obesity and hypertension. Antibiotic use within the past 30 days did not seem to have an effect on the types of bacteria detected on the stents.

"While more research is needed, our study suggests that antibiotic use during the placement of these stents could one day be more conservative or targeted based on each patient's condition," says Dr. Jeremy Burton, Lawson Scientist and Associate Professor at Schulich Medicine & Dentistry.

The team also discovered that in patients needing multiple stents, the bacterial community remained stable over time, suggesting that infections on a patient's previous stent could direct the course of treatment for their future device placements.

"This is the largest study of its kind, investigating bacteria both in urine and adhered to ureteral stents," states Dr. Hassan Razvi, Urologist at St. Joseph's, Lawson Associate Scientist and Professor at Schulich Medicine & Dentistry. "We hope this will be the first step towards personalized care, ultimately leading to fewer stent-associated infections."

Experts from the Department of Prehistory and Archaeology of the University of Seville have just published a study in the prestigious journal PLOS ONE on an important archaeological find in the Cueva de la Dehesilla (Cádiz). Specifically, two human skulls and a juvenile goat were discovered along with various archaeological structures and materials from a funerary ritual from the Middle Neolithic period (4800-4000 BC) hitherto unknown in the Iberian Peninsula.

"This finding opens new lines of research and anthropological scenarios, where human and animal sacrifice may have been related to ancestral cults, propitiatory rituals and divine prayers in commemorative festivities," explains US researcher Daniel García Rivero.

The archaeological site located in the Cueva de la Dehesilla consists of two adult human skulls, one male one female, the former being older. The female skull shows a depression in the frontal bone, which probably comes from an incomplete trepanation, as well as cuts in the occipital bone produced by decapitation. In addition, a wall was found separating the human skulls and the skeleton of the goat, on the one hand, from a stone altar with a stele and a hearth, on the other. Finally, several uniquely decorated ceramic vessels, some lithic objects and charred plant remains were discovered in the so-called Locus 2.

"These elements display various characteristics that make it an exceptional archaeological find. The differential treatment of skulls with traumatological evidence along with sacrificed animals, as well as the documented archaeological structures and materials do not match the normative funerary record we were working with until now. This discovery is of great importance not only because of its peculiarity, but also because it constitutes a sealed, intact ritual deposit, which is a great opportunity to gain a more detailed insight into the funerary and ritual behaviours of the Neolithic populations of the Iberian Peninsula", emphasises professor García Rivero.

Neolithic funeral rituals

This work contributes in a particular way to the knowledge of the funerary rituals of the middle part of the 5th millennium before Christ, currently the least well known period of the Neolithic populations of the Iberian Peninsula as a whole. The scarce funerary record from that time shows fundamentally individual burials, with secondary burials being unusual. The sort of context just discovered is really extraordinary. Burials usually occur in areas of habitat, and are mostly associated with remains of ceramics and shells, as well as homes, which reflect the importance of activities related to the use of fire, but without stone structures like those now documented in the mountains of Cádiz.

The study and review of the entire funerary record of this period allows us to offer a kind of cultural mosaic in relation to the funerary and ritual traditions of these peasant and herding populations, with a probable division between the Andalusian region and the eastern seaboard of the peninsula, the two regions where most data is available today.

Escherichia coli, known as E. coli, are bacteria which many people associate with causing mild food poisoning, but some types of E. coli can be fatal.

UNSW Science microbiologists studied an E. coli strain that causes a severe intestinal infection in humans: enterohemorrhagic E. coli (EHEC). Their findings were published this week in the journal PNAS (Proceedings of the National Academy of Sciences).

EHEC is a food-borne pathogen that releases Shiga toxins during infection, resulting in kidney and neurological damage.

Dr Jai Tree, the study's senior author, said the researchers' discovery of a new molecular pathway that controls Shiga toxin production was important because there was no commercially available treatment for EHEC infections.

"Antibiotic treatment of these infections is generally not recommended because antibiotics stimulate production of the Shiga toxin, leading to an increased risk of kidney failure, neurological damage, and death," Dr Tree said.

"The new pathway that we have found reduces toxin production and is not expected to be stimulated by antibiotic treatment. So, our results identify a potential new target for the development of drugs that can suppress Shiga toxin production during EHEC infection.

"It's still early days, however, and we need to conduct a lot more research to understand if our findings apply to a broad range of clinical EHEC isolates and to both types of Shiga toxins produced by human EHEC isolates."

How EHEC infections start

Dr Tree said there were several ways in which people could become infected with EHEC.

"EHEC is mainly found in the faeces of cows and sheep and people can become infected through contact with farm animals and their faeces, or via person-to-person infection if people come into contact with tiny amounts of faeces from a sick person - for example, directly or indirectly by touching contaminated surfaces," he said.

"This strain of E. coli can also spread through ingesting the bacteria by eating undercooked minced meat (for example, in hamburgers), eating contaminated fresh produce like salad vegetables, or drinking contaminated water or unpasteurised milk.

"Children under five years old and older people are at greatest risk of developing an EHEC infection."

EHEC outbreaks less common but deadly

Dr Tree said while the prevalence of EHEC was low compared to other foodborne pathogens, the disease could be very severe or even fatal. EHEC is a type of STEC (Shiga toxin-producing Escherichia coli).

"EHEC outbreaks occur sporadically in Australia and worldwide. The most significant outbreak occurred in South Australia in 1995 and was caused by contaminated mettwurst, a semi-dry fermented sausage made from raw minced pork preserved by curing and smoking," he said.

"In that outbreak, 143 people were infected - 23 of them suffered kidney and neurological damage. Many of these severe cases were in infants who suffered permanent kidney damage and later required kidney transplants.

"A four-year-old girl suffered multiple strokes and died three days after admission to hospital. This episode triggered a major food safety investigation and outbreaks since 1995 have been smaller."

Dr Tree said globally, Shiga toxin-producing E. coli was still a major food safety concern after a large outbreak in Germany in 2011.

"The strain in Germany was spread mostly via consumption of contaminated sprouts and in several cases, from close contact with an infected person," he said.

"During this outbreak more than 4000 people were infected and 50 people died."

New pathway 'hiding in plain sight'

Dr Tree said the UNSW research was the first discovery of a new pathway that controls the Shiga toxins in almost 20 years.

"In 2001, researchers at Tufts and Harvard universities first showed how production of the Shiga toxin was controlled by a bacterial virus, known as a bacteriophage, within the genome. This has been the only known pathway that controls Shiga toxin production for almost two decades," he said.

"We have extended that work to show a new mechanism of toxin control that is, surprisingly, buried within the start of the DNA sequence that encodes the Shiga-toxin messenger RNA - a working copy of the gene.

"We discovered a very short piece of the toxin messenger RNA is made into a regulatory non-coding RNA that silences the toxin and promotes growth of the pathogen."

Dr Tree said their findings were a surprise because Shiga toxin genes have been well studied, with almost 7000 published studies in the past 40 years.

"Only recently have we been able use advances in RNA sequencing technology to detect the presence of the new regulatory non-coding RNA embedded within the Shiga toxin messenger RNA," he said.

"This new regulatory non-coding RNA had been hiding in plain sight for almost 20 years."

Implications for treating EHEC infections

Dr Tree said the researchers' findings opened up new possibilities for the treatment of EHEC infections.

"Patients largely receive supportive care to manage disease symptoms and to reduce the effects of the toxin on the kidneys," he said.

"Our work shows a new mechanism for controlling toxin production that may be amenable to new RNA-based therapeutics to inhibit toxin production during an infection. We anticipate this would expand intervention options and potentially allow use of antibiotics that are currently not recommended because they stimulate Shiga toxin production.

"New treatments could therefore reduce the risk of kidney damage, neurological complications and death. We look forward to testing these new interventions in the next stage of our research."

New research from the University of Sydney finds that even low levels of alcohol consumption during pregnancy can have an impact on a child's brain development and is associated with greater psychological and behavioural problems in youth including anxiety, depression and poor attention.

Published today in the prestigious American Journal of Psychiatry, the study was led by the University's Matilda Centre for Research in Mental Health and Substance Use.

The impact of low-level alcohol use during pregnancy on child development is relatively unknown and there has been extensive debate about whether there is a safe level of consumption.

The researchers investigated whether any alcohol consumption in pregnancy was related to psychological, behavioural, neural and cognitive differences in children aged nine to ten years. With a sample of 9,719 youth, this is the largest study to investigate the impacts of low-level alcohol use during pregnancy. Low levels of drinking were considered one to two drinks per occasion with maximum of six drinks per week.

"Our research found that even small amounts of alcohol consumed while pregnant can have a significant impact on a child's brain development," said lead author Ms Briana Lees, PhD candidate at the Matilda Centre.

"Previous research has shown that very heavy alcohol use, such as binge drinking, during pregnancy can cause harm to the baby. However, this study shows that any alcohol use during pregnancy, even low levels, is associated with subtle, yet significant behavioural and psychological effects in children including anxiety, depression and poor attention.

"This study is so important because in Australia, around 50 percent of women drink alcohol before they know they are pregnant, and 25 percent do so after they know. The vast majority consume one or two standard drinks per occasion which this study shows is enough to impact the baby's brain."

Study findings

In the study, 25 percent of children had been exposed to alcohol in utero (in the womb), 60 percent of these children had been exposed to low-level alcohol use, and 40 per cent had been exposed to heavier levels. Heavier exposure being three or more drinks per occasion or seven or more drinks per week.

Children who were exposed to low levels of alcohol in-utero at any time during pregnancy experienced more psychological/emotional problems (including anxiety, depression and being withdrawn) and behavioural problems (including poor attention and being impulsive) than unexposed children.
There was a 25 percent increased likelihood of an attention deficit hyperactivity disorder (ADHD) diagnosis in children who were exposed to slightly heavier levels of alcohol (approximately 36 drinks) in the first 6-7 weeks of pregnancy.
Heavier alcohol use during early pregnancy was also associated with rule breaking behaviour and aggression, with a 30 percent higher risk of the child being diagnosed with oppositional defiant disorder than unexposed youth.

There were differences observed in brain volume and surface area among the exposed children which contributed to the psychological and behavioural problems.
The estimated number of drinks consumed during pregnancy ranged from 0-90 with the average being 27. The majority of drinks were consumed in the first 6-7 weeks prior to pregnancy knowledge.

"Generally, the more a child was exposed to alcohol in utero the more severe the outcomes were," said Ms Lees.

"Children experienced negative effects even if they were only exposed to low levels of alcohol during very early pregnancy (approximately 16 drinks in the first six to seven weeks) and then the mother stopped drinking. The difficulty is many women don't know they are pregnant at that early stage.

Senior author Professor Maree Teesson, Director of the Matilda Centre said these findings are important for families, clinicians and policy makers moving forward.

"This research highlights the importance for women to be aware of the effects that even low levels of drinking can have on the brain development of babies," she said.

"The safest option during pregnancy is to abstain from drinking any alcohol.

"This information is also important for women planning pregnancies. Even when planning pregnancy, it is safer to abstain from any drinking. Any alcohol consumption from conception throughout the entire pregnancy can impact the brain development of their baby."

AMES, Iowa - Computer simulations are showing astrophysicists how massive clumps of gas within galaxies scatter some stars from their orbits, eventually creating the smooth, exponential fade in the brightness of many galaxy disks.

Researchers from Iowa State University, the University of Wisconsin-Madison and IBM Research have advanced studies they started nearly 10 years ago. They originally focused on how massive clumps in young galaxies affect star orbits and create galaxy disks featuring bright centers fading to dark edges.

(As Curtis Struck, an Iowa State professor of physics and astronomy, wrote in a 2013 research summary: "In galaxy disks, the scars of a rough childhood, and adolescent blemishes, all smooth away with time.")

Now, the group has co-authored a new paper that says their ideas about the formation of exponential disks apply to more than young galaxies. It's also a process that is robust and universal in all kinds of galaxies. The exponential disks, after all, are common in spiral galaxies, dwarf elliptical galaxies and some irregular galaxies.

How can astrophysicists explain that?

By using realistic models to track star scattering within galaxies, "We feel we have a much deeper understanding of the physical processes that resolve this almost-50-year-old key problem," Struck said.

Gravitational impulses from massive clumps alter the orbits of stars, the researchers found. As a result, the overall star distribution of the disk changes, and the exponential brightness profile is a reflection of that new stellar distribution.

The astrophysicists' findings are reported in a paper just published online by the Monthly Notices of the Royal Astronomical Society. Co-authors are Struck; Jian Wu, an Iowa State doctoral student in physics and astronomy; Elena D'Onghia, an associate professor of astronomy at Wisconsin; and Bruce Elmegreen, a research scientist at IBM's Thomas J. Watson Research Center in Yorktown Heights, New York.

Stars are scattered, disks are smoothed

The latest computer modeling - led by Wu - is a capstone topping years of model improvements, Struck said. Previous models treated the gravitational forces of galaxy components more approximately, and researchers studied fewer cases.

The latest models show how star clusters and clumps of interstellar gases within galaxies can change the orbits of nearby stars. Some star-scattering events significantly change star orbits, even catching some stars in loops around massive clumps before they can escape to the general flow of a galaxy disk. Many other scattering events are less powerful, with fewer stars scattered and orbits remaining more circular.

"The nature of the scattering is far more complex than we previously understood," Struck said. "Despite all this complexity on small scales, it still averages out to the smooth light distribution on large scales."

The models also say something about the time it takes for these exponential galaxy disks to form, according to the researchers' paper. The types of clumps and initial densities of the disks affect the speed of the evolution, but not the final smoothness in brightness.

Speed in this case is a relative term because the timescales for these processes are billions of years.

Over all those years, and even with model galaxies where stars are initially distributed in a variety of ways, Wu said the models show the ubiquity of the star-scattering-to-exponential-falloff process.

"Stellar scattering is very general and universal," he said. "It works to explain the formation of exponential disks in so many cases."

Quebec and Montreal, September 25, 2020 - The relationship between the income levels of parents and their children once they reach adulthood is complex, but education could be one of the factors that influence Canadian intergenerational mobility. This according to a study recently published by INRS (Institut national de la recherche scientifique) professor Xavier St-Denis and Statistics Canada researcher Gaëlle Simard Duplain in Canadian Public Policy/Analyse de politiques. The study looks at the role education levels play in intergenerational income mobility in Canada.

Most studies available on the subject present results based on national or regional income mobility, which can be used to make geographic and historical comparisons. "The underlying mechanisms at play in the relationship between the income of parents and the income of their children, including their education levels and job characteristics, hasn't been studied much in Canada," explained Professor St-Denis.

To measure the effects of education on intergenerational mobility in Canada, the two researchers looked at the data from Statistics Canada's Longitudinal and International Study of Adults (LISA), which covers the period from 1982 to 2014. "Our study shows that in Canada, a child's education level explains 40.5% to 50.1% of the correlation between a child's income once they reach adulthood and their parent's income," said Professor St-Denis. "That's similar to the results observed in the United States and the UK."

Income inequality repeated from one generation to the next

According to the research results, social and economic inequalities occur early in life and have long-lasting effects.

The results also point to the existence of differentiation mechanisms that operate throughout the working lives of people with similar levels of education. "Intergenerational mobility partly results from the different characteristics in a child's environment, from their cumulative and complementary effects. It also results from the time, financial resources, and social capital that parents with a higher income are more likely to invest in their children's education," said Professor St-Denis, who recently joined INRS's Urbanisation Culture Société Research Centre.

If the income of people living in a society is only marginally dependent on their parents' income, that society is said to have a high degree of intergenerational mobility. In other words, the context in which children grow and evolve does not depend solely on their parents' economic situation. Access to education, for example, could depend not on parents' ability to pay for it, but on the child's interest in pursuing their studies.

Inversely, when the income of individuals in adulthood is, on average, similar to that of their parents, inequalities are reproduced to a much greater degree from one generation to the next. This can result in intergenerational income immobility.

A mix of ultrapotent antibodies from recovered COVID-19 patients has been shown to recognize and lock down the infection machinery of the pandemic coronavirus and keep it from entering cells. Each of the antibody types performs these overlapping tasks slightly differently.

Low doses of these antibodies, individually or as a cocktail, were also shown to protect hamsters from infection when exposed to the coronavirus by preventing it from replicating in their lungs.

An advantage of such cocktails is that they might also prevent the natural mutant forms of the virus that arose during this pandemic to escape treatment. As some variants in the infection machinery have already been discovered during the coronavirus pandemic, using a mix of antibodies allows for neutralization of a broad spectrum of such viral variants.

In addition to preventing virus entry into host cells, the presence of the antibodies also seems to set off the infection-fighting actions of other immune cells, which arrive to clear out the virus.

"We believe that leveraging multiple, distinct, complementary mechanisms of action could provide additional benefits for clinical applications," the researchers noted.

The researchers determined how the antibodies worked on a molecular level through cryo-electron microscopy studies of the resulting changes in the configuration of the virus infection machinery. Besides directly preventing interactions with the host receptor, one of the two discovered antibodies locks the infection machinery in an inactive conformation, meaning it could not fuse with the host membrane on the surface of the cell. If unable to fuse, the coronavirus cannot break in and deliver its RNA to commandeer the cell.

The findings of this research are reported Sept. 24 in a rapid release paper in Science. Here is the paper.

The senior authors were Dr. Katja Fink of Vir Biotechnology and Dr. David Veesler, associate professor of biochemistry at the University of Washington School of Medicine. Veesler has studied the molecular structure and infection mechanisms of a variety of coronaviruses and other viruses.

The lead authors were M. Alejandra Tortorici of the UW Department of Biochemistry and the Institut Pasteur in Paris, and Martina Beltramello of Humab BioMed, a subsidiary of Vir Biotechnology in Switzerland. Researchers from Washington University in St Louis, Rega Institute in Belgium, the University of Milan, Italy, and the University of Texas in Dallas also collaborated on the research.

Efficient therapeutic options are needed to control the spread of SARS-CoV-2 that has caused more than 978,000 fatalities worldwide. While the world awaits approved vaccines, pharmaceuticals to prevent or treat infections from the pandemic coronavirus are being sought that might be quicker to develop and test. These might both address the gap until vaccines are widely distributed, and still be needed for use after vaccines are available.

"Our results pave the way to implement antibody cocktails for prophylaxis or therapy that might have the advantage of circumventing or limiting the emergence of viral escape mutants," the researchers noted. The antibody cocktail in their study needs to undergo trials in humans to determine safety and effectiveness.

As 2020 began, many pundits predicted a politically charged year, but few predicted that it would include a global pandemic overtaxing healthcare resources, strained U.S. race relations resulting in mass demonstrations across the globe, devastating fires consuming massive swaths of the United States, and a catastrophic global economic downturn. This month's special issue of the Journal of Public Policy & Marketing acknowledges the role that marketing does and can play in addressing political activities with articles that explore key topics like elections, voting, corporate political advocacy, and consumer political identities. Two commentaries from an industry veteran and an esteemed journal editor offer both applied and scholarly paths for future marketing strategies and research. While the articles were not intended to respond directly to the specific events, they still provide theories explaining firm, consumer, agency, and other stakeholder behaviors along with strategy implications.

"A Vote of Competence: How a Similar Upbringing to Political Candidates Influences Voting Choice," by Matthew D. Meng and Alexander Davidson

The authors explore a commonly used political strategy: showing how similar political candidates are to constituents and voters. The authors confirm this relationship but expand the understanding as it relates to a candidate's competence along with particular audiences for whom the strategy is most effective.

https://doi.org/10.1177/0743915620943181

"Citizen Participation in Political Markets: Extending Service-Dominant Logic to Public Policy," by Mark Peterson and Robert W. Godby

The results of this study suggest that the decisions offered by citizens in a research setting reflect citizens' competence for informing elected representatives and policy makers regarding budgeting. When constituents can be brought into the process of ongoing governance in an effective and manageable fashion that does not require an expensive referendum or election, distortions of democracy will be reduced.

https://doi.org/10.1177/0743915620912287

"To Change the Law, Defy the Law: Hijacking the Cause and Co-Opting Its Advocate," by Bernard Cova

This research examines how the advocates of a cause respond to corporate approaches that integrate marketing and political activities for the cause. The findings reveal that such marketing activities resemble co-optation of the initial advocate of the cause and hijacking of the cause they advocate for.

https://doi.org/10.1177/0743915620943855

"Brands Taking a Stand: Authentic Brand Activism or Woke Washing?" by Jessica Vredenburg, Sommer Kapitan, Amanda Spry, and Joya A. Kemper

The authors draw on theory to determine how and when a brand engaging with a sociopolitical cause can be viewed as authentic, finding that moderate, optimal incongruence between brand and cause acts as a boundary condition. They explore important policy and practice implications for current and aspiring brand activists, from specific brand-level standards in marketing efforts to third-party certifications and public sector partnerships.

https://doi.org/10.1177/0743915620947359

"The Activist Company: Examining a Company's Pursuit of Societal Change Through Corporate Activism Using an Institutional Theoretical Lens," by Meike Eilert and Abigail Nappier Cherup

Using institutional theory, the authors create a framework showing how corporate activism can address these societal problems through influence and change strategies that can target the institutional environment "top-down" or "bottom-up." This framework further investigates how the company's identity orientation facilitates corporate activism.

https://doi.org/10.1177/0743915620947408

"Political Ideology in Consumer Resistance: Analyzing Far-Right Opposition to Multicultural Marketing," by Sofia Ulver and Christofer Laurell

The authors explore the discursive efforts in far-right consumer resistance to advance a political agenda through protests directed at brands' multicultural advertising and analyze how these consumers conceptualize their adversaries in the marketplace. In contrast to previous framings of adversaries identified in consumer research, where resistance is typically anticapitalist and directed toward firms' unethical conduct or the exploitation by the global market economy per se, the authors find that the following discursive themes stand out in the far-right consumer resistance: the emphasis on the state as main antagonist, the indifference to capitalism as a potential adversary, and overt contestation of liberal ethics.

https://doi.org/10.1177/0743915620947083

"Politics at the Mall: The Moral Foundations of Boycotts," by Daniel Fernandes

This article demonstrates that although both liberals and conservatives engage in consumer political actions, they do so for different reasons influenced by their unique moral concerns: Liberals engage in boycotts and buycotts that are associated with the protection of harm and fairness moral values (individualizing moral values), whereas conservatives engage in boycotts and buycotts that are associated with the protection of authority, loyalty, and purity moral values (binding moral values). In addition, the individualizing moral values lead to a generally more positive attitude toward boycotts, which explains why liberals are more likely to boycott and buycott.

https://doi.org/10.1177/0743915620943178

"Commentary: Brand Activism in a Political World," by Christine Moorman

The Editor in Chief of the venerable Journal of Marketing and author of "The CMO Survey" analyzes CMO's changing opinions on firm activism.

https://doi.org/10.1177/0743915620945260

"Commentary: Patagonia and the Business of Activism," by Vincent Stanley

Patagonia's Director of Philosophy discusses the brand's decision to take public stands on critical issues such as climate change.

https://doi.org/10.1177/0743915620943181

For the full issue and contact information, visit https://journals.sagepub.com/toc/ppoa/39/4.

TAMPA, Fla. (Sept. 25, 2020) - As COVID-19 quickly spread worldwide this spring, shortages of supplies, including the nasopharyngeal (nasal) swabs used to collect viral samples, limited diagnostic testing.

Now, a multisite clinical trial led by the University of South Florida Health (USF Health) Morsani College of Medicine and its primary hospital affiliate Tampa General Hospital (TGH) provides the first evidence that 3D-printed alternative nasal swabs work as well, and safely, as the standard synthetic flocked nasal swabs.

The results were published online Sept. 10 in Clinical Infectious Diseases. A commentary accompanying the paper cites the authors' timely, collaborative response to supply chain disruptions affecting testing capacity early in the pandemic.

Seeking a solution to an unprecedented demand for nasal swabs at their own institution and others, USF Health researchers in the Departments of Radiology and Infectious Diseases reached out to colleagues at TGH; Northwell Health, New York's largest health care provider; and leading 3D-printer manufacturer Formlabs. Working around the clock, this multidisciplinary team rapidly designed, tested and produced a 3D printed nasal swab prototype as a replacement for commercially-made flocked nasal swabs. Bench testing (24-hour, 3-day, and leeching) using respiratory syncytial virus as a proxy for SARS-CoV-2, as well as local clinical validation of the final prototype (fabricated with FDA-approved nontoxic, surgical grade materials), was successfully completed in mid-March 2020.

The larger-scale clinical trial began in late March at three sites: TGH, Northwell Health, and Philadelphia-based Thomas Jefferson University Hospital. (Other sites joined later.)

Although USF Health held a provisional patent on the concept and design of the new 3D printed swab, they freely shared the information with hospitals, clinics, governments and international agencies experiencing supply chain shortages. Since the first batches of 3D printed swabs were processed, tens of millions of the USF Health-invented devices have been used in 22 countries, said lead author Summer Decker, PhD, an associate professor of radiology at the USF Health Morsani College of Medicine. Dr. Decker directs the USF Health Radiology-TGH Division of 3D Clinical Applications, a group with expertise in creating and printing 3D anatomical models for surgeons and other clinicians as well as designing medical devices.

"In the midst of a pandemic, our team of experts representing academic medicine, health care delivery systems, and the medical device industry put aside boundaries to quickly work together toward a common purpose," Dr. Decker said. "It's rewarding that the novel design for a 3D swab we created has been adopted around the world, equipping more providers to diagnose COVID-19 and hopefully help prevent its spread."

The gold standard for diagnosing respiratory infections is to look for viral genetic material found in mucosal fluid collected with a long, slender swab inserted into the patient's nose and back of the throat. The nasal swab is put into a plastic tube with chemicals that stabilize the sample until the virus-specific genetic material can be extracted and amplified by polymerase chain reaction (PCR) in a diagnostics laboratory. Conventional swabs feature a bushy tip coated with nylon flock; the USF Health doctors designed a tip with a 3D printed textured pattern able to capture a sufficient sample for COVID testing while keeping patient safety and comfort in mind.

The clinical trial fully tested the safety and effectiveness of this 3D printed swab in 291 symptomatic adults undergoing COVID-19 screening at the TGH, Northwell Health and Thomas Jefferson University Hospital sites. The 3D printed nasal swab was compared to the standard synthetic nasal swab across three SARS-CoV-2 testing platforms FDA-authorized for emergency use -- a modified version of the Center for Disease Control and Prevention's real-time reverse transcriptase PCR diagnostic panel, and two commercial molecular diagnostic tests.

"This trial provided the first rigorous head-to-head comparison to make sure that the 3D swab performed as well as the standard," said principal investigator Kami Kim, MD, professor and division director for infectious disease at the USF Health Morsani College of Medicine. "Across all three platforms used in our study, we demonstrated that the commercial swab and the 3D printed swab were comparable for accurate detection of COVID-19 infection."

For both swabs, the only adverse patient reaction documented during the trial was a few instances of slight nasal bleeding. The cost of materials per 3D printed nasal swab ranges from 26-to 46-cents, while commercial swabs cost about $1 each, the authors reported.

Given the ongoing need for widespread COVID-19 testing, the study authors concluded that 3D printing technology offers a viable, cost-efficient option to address swab supply shortages, particularly when local hospitals or other clinical sites already have 3D printing labs equipped to print and process the devices.

Frank Rybicki, MD, PhD, vice chair of operations and quality at the University of Cincinnati College of Medicine's Department of Radiology, wrote a commentary on 3D printing in medicine to accompany the Clinical Infectious Diseases paper. The article frames the contributions of Decker et. al. in the context of the larger 3D manufacturing community.

"Among all parts 3D printed during COVID-19, nasopharyngeal swabs have received the most attention, with participants ranging from humanitarians to charlatans," Dr. Rybicki wrote in his summary. "The authors should be congratulated for staying on the right side of the curve, and for their perseverance, leadership, scientific rigor, and good will."