Body

Supercharged ‘clones’ spark scarlet fever’s re-emergence

image: The University of Queensland's Dr Stephan Brouwer is helping reveal why scarlet fever is making a comeback.

Image: 
The University of Queensland

A University of Queensland-led team of international researchers says supercharged “clones” of the bacteria Streptococcus pyogenes are to blame for the resurgence of the disease, which has caused high death rates for centuries.

UQ’s Dr Stephan Brouwer said health authorities globally were surprised when an epidemic was detected in Asian countries in 2011.

“The disease had mostly dissipated by the 1940s,” Dr Brouwer said.

“Like the virus that causes COVID-19, Streptococcus pyogenes bacteria are usually spread by people coughing or sneezing, with symptoms including a sore throat, fever, headaches, swollen lymph nodes, and a characteristic scarlet-coloured, red rash.

“Scarlet fever commonly affects children, typically aged between two and 10 years.

“After 2011, the global reach of the pandemic became evident with reports of a second outbreak in the UK, beginning in 2014, and we’ve now discovered outbreak isolates here in Australia.

“This global re-emergence of scarlet fever has caused a more than five-fold increase in disease rate and more than 600,000 cases around the world.”

Co-author Professor Mark Walker and the team found a variety of Streptococcus pyogenes bacteria that had acquired “superantigen” toxins, forming new clones.

“The toxins would have been transferred into the bacterium when it was infected by viruses that carried the toxin genes,” Professor Walker said.

“We’ve shown that these acquired toxins allow Streptococcus pyogenes to better colonise its host, which likely allows it to out-compete other strains.

“These supercharged bacterial clones have been causing our modern scarlet fever outbreaks.

“The research team then removed the toxin genes from the clones causing scarlet fever, and these modified 'knock-out' clones were found to be less able to colonise in an animal model of infection.”

For the time being, scarlet fever outbreaks have been dampened, largely due to public health policy measures introduced to control COVID-19.

“This year COVID-19 social distancing has kept scarlet fever outbreaks in check for now,” Professor Walker said.

“And the disease’s main target – children – have been at school less and also spending far less time in other large groups.

“But when social distancing eventually is relaxed, scarlet fever is likely to come back.

“We need to continue this research to improve diagnosis and to better manage these epidemics.

“Just like COVID-19, ultimately a vaccine will be critical for eradicating scarlet fever – one of history’s most pervasive and deadly childhood diseases.”

Credit: 
University of Queensland

New aerosol research indicates significantly less risk of COVID-19 transmission from

Since the outset of the COVID-19 pandemic, there has been much debate about the danger to hospital staff from anaesthetic procedures. Concerns include that placing a tube in the patient's airway (intubation) before surgery or removing it at the end (extubation) may produce a fine mist of small particles (called aerosols) and spread the COVID-19 virus to nearby staff.

This risk was judged so high that the procedures are classified 'aerosol generating procedures' (AGPs) for which respirators and high level personal protective equipment (PPE) are worn routinely, and after which surgery stops while the operating room is cleared of aerosols and special cleaning is undertaken. These requirements have dramatically slowed surgery and contributed to enormous waiting lists for surgery in the UK National Health Service (NHS), as well as similar problems in hospitals worldwide. Despite the presumed risk, no direct measurements of aerosols have ever been made during anaesthetic care in a hospital.

New research published in Anaesthesia (a journal of the Association of Anaesthetists) shows that these procedures may only produce a fraction of the aerosols previously thought, much less than would be produced during a single regular cough. This brings into question whether the procedures should be designated AGPs and provides an opportunity to dramatically speed up surgery.

The study is by Dr Jules Brown (North Bristol NHS Trust, Bristol, UK) working with Professor Jonathan Reid (Bristol Aerosol Research Centre, School of Chemistry, University of Bristol), Professor Tim Cook (Royal United Hospitals Bath NHS Foundation Trust, Bath, UK, and School of Medicine, University of Bristol, UK) and Professor Tony Pickering, (School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, UK), and colleagues.

To address this lack of evidence, the authors conducted real-time, high-resolution environmental monitoring in ultraclean ventilation operating theatres during anaesthesia procedures for insertion and removal of the tube from the patient's airway. The authors also studied procedures such as suction of the airway and 'mask ventilation' when the anaesthetist takes over the patients breathing before tube insertion. Put simply, they were able to quantify the aerosols generated during all these procedures, in a real clinical setting, and compare this to the aerosols produced by a single cough. Recordings were made of 19 tube insertions and 14 tube removals.

Against expectations, the authors found that tube insertion generated approximately one thousandth of the aerosol generated by a single cough. Tube removal produced more aerosol, especially when accompanied by a weak cough, but still less than 25% of that produced by a voluntary cough.

"These findings should trigger a re-evaluation of when it is necessary to use specific measures to protect against viral transmission by aerosol in operating rooms. De-escalation of these high-level protective measures would have a substantial impact on our ability to deliver healthcare to patients within the NHS and internationally," explain the authors.

"If we can agree these procedures do not generate aerosols we can reduce the PPE we wear and we can eliminate the major delays that currently exist between one patient leaving the operating room and starting the next case," they add.

"The results suggest that during anaesthesia tube insertion should not be considered a high-risk procedure," say the authors. "We detected no increases in aerosolised particles during face-mask ventilation, airway suction or repeated attempts at intubation. This reflects typical clinical practice by anaesthetists with a range of experience, providing further reassurance regarding the low level of aerosol generation."

The authors explain that with tube removal, a cough can occur as the patient's natural breathing reflexes return, and this does produce aerosols that are detectable for around five seconds. They say: "The risk of aerosol exposure for staff can be further reduced by using techniques that reduce coughing or by the anaesthetist simply stepping away, as our study showed much reduced particle numbers behind the patient's head compared to above their face."

The authors note some limitations to their study. "It should be acknowledged that while we have provided reassuring evidence around aerosol generation during these procedures, we have not directly studied the risk of SARS-CoV-2 transmission and our interpretation rests on the widely accepted link between aerosol generation and infection risk," they explain. For safety reasons, this study was not performed on patients with COVID-19, but on other patients to demonstrate the aerosols actually produced during these procedures which are common during anaesthesia and in intensive care.

They conclude: "The precautions many hospitals worldwide have introduced to mitigate the risks posed by viral aerosols have reduced operating theatre turnover, decreased hospital productivity and increased waiting times for elective and cancer surgery. A further important consideration relates to the cost and limited supply of PPE which has to be targeted to appropriate healthcare settings on the basis of risk. Our results raise important questions about the need for these precautions at the start and end of anaesthesia. These results should help inform future PPE guidelines by providing evidence on the relative risk of aerosol generation associated with tracheal intubation and extubation."

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AAGBI

Fostamatinib in chronic immune thrombocytopenia: No comparison -- added benefit not proven

Fostamatinib is approved for the treatment of chronic immune thrombocytopenia in adults who are refractory to other treatments (in particular to treatment with corticosteroids). The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in an early benefit assessment whether fostamatinib offers an added benefit for these patients in comparison with eltrombopag or romiplostim.

The drug manufacturer recognized both drugs as appropriate comparator therapy, but presented neither direct nor indirect comparisons between fostamatinib and the appropriate comparator therapy. IQWiG therefore concluded that an added benefit is not proven.

Comparisons with appropriate comparator therapy necessary

The approval studies, the data of which the manufacturer cited in its dossier, compared fostamatinib with placebo. Randomized controlled trials with direct comparisons between fostamatinib and eltrombopag or romiplostim are not available. The manufacturer did not identify any suitable data for an adjusted indirect comparison.

Comparisons with the appropriate comparator therapy are necessary, however, to understand the benefit and harm that the different treatment options have for the patients in relation to each other. They are the backbone of the early benefit assessment: There is no other way to determine an added benefit of the drug in comparison with the current standard treatment.

G-BA decides on the extent of added benefit

The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA). After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.

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Institute for Quality and Efficiency in Health Care

Promising treatment for aggressive childhood cancer

A drug has shown great promise in the treatment of neuroblastoma, an aggressive form of childhood cancer. The study was led by researchers at Lund University in Sweden, and is published in the journal Science Translational Medicine.

Every year, about 800 children in the US are diagnosed with neuroblastoma, an aggressive cancer of the nervous system that most frequently arises in the adrenal glands. Despite intensive chemotherapy, the disease can be difficult to cure and the prognosis is often poor. However, researchers at Lund University have now identified and tested a drug that has been shown to be very effective against neuroblastoma.

"Initially we conducted a large-scale drug screen where we examined how 500 drugs affected neuroblastoma cells from patients. Most of these medications have never before been used on patients with neuroblastoma", says Karin Hansson, doctoral student and first author of the study.

The researchers then obtained a "short list" of the most effective drugs. One of these was a so-called KSP inhibitor, particularly interesting as patients with a high proportion of KSP protein have the more aggressive variant of neuroblastoma, something that is synonymous with a worse prognosis.

When the researchers treated mice with this drug, they saw how the KSP inhibitor prevented tumour growth and drastically prolonged survival. In some cases, the tumour disappeared completely. KSP inhibitors block the protein in tumour cells, meaning that the cells can no longer divide and therefore eventually die.

The KSP inhibitor has not previously been used for neuroblastoma, but was shown to be extra effective against this type of cancer. It also did not affect healthy bone marrow cells, which is important as side effects are a major problem in childhood cancer therapies.

"The results were very clear and the treatment is very promising. But even so, there will probably be a need to combine this treatment with other drugs to completely knock out all tumour cells. Fortunately, the drug is already approved for use in humans. Now, of course, we hope that clinical trials for neuroblastoma will be initiated", concludes Daniel Bexell, associate professor and research group leader at Lund University.

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Lund University

Imaging technique could replace tissue biopsies in assessing drug resistance in cancer

image: False colour image of a breast tumour (outlined) pre- and post-treatment with a PI3Ka inhibitor. Weaker colours post-treatment indicate that the drug is working.

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Brindle Lab, University of Cambridge

Imaging techniques could replace the need for invasive tissue biopsies in helping rapidly determine whether cancer treatments are working effectively, according to researchers at the University of Cambridge.

In a study published in the journal Cancer Cell, researchers at the Cancer Research UK (CRUK) Cambridge Institute have shown how a new technique known as hyperpolarisation - which involves effectively magnetising molecules in a strong magnetic field - can be used to monitor how effective cancer drugs are at slowing a tumour's growth.

In healthy tissue, cell proliferation is a tightly controlled process. When this process goes wrong, cell proliferation can run away with itself, leading to unchecked growth and the development of tumours.

All tissue needs to be 'fed'. As part of this process - known as metabolism - our cells break down glucose and other sugars to produce pyruvate, which is in turn converted into lactate. This is important for producing energy and the building blocks for making new cells.

Tumours have a different metabolism to healthy cells, and often produce more lactate. This metabolic pathway is affected by the presence of a protein known as FOXM1, which controls the production of a metabolic enzyme that converts pyruvate into lactate. FOXM1 also controls the production of many other proteins involved in cell growth and proliferation.

Around 70% of all cases of breast cancer are of a type known as estrogen-receptor (ER) positive. In many ER-positive breast cancer cases, an enzyme known as PI3K? is activated. This leads to an abundance of FOXM1, enabling the cancer cells to grow uncontrollably - the characteristic sign of a tumour cell.

Drugs that inhibit PI3K? are currently being tested in breast cancer patients. Such drugs should be able to decrease the amount of FOXM1 and check the tumour's growth. However, a patient's tumour may have an innate resistance to PI3K? inhibitors, or can acquire resistance over time, making the drugs increasingly less effective.

Dr Susana Ros, first author from the CRUK Cambridge Institute, said: "Thanks to advances in cancer treatments, our medicines are becoming more and more targeted, but not all drugs will work in every case - some tumours are resistant to particular drugs. What we need are biomarkers - biological signatures - that tell us whether a drug is working or not."

The researchers took breast cancer cells from patients and grew them in mouse 'avatars' to allow them to study the tumours in detail. They found that in tumours resistant to PI3K? inhibitors, cancer cells continue to produce FOXM1 - meaning that this molecule could be used as a biomarker for drug resistance in patients with ER-positive breast cancer.

Checking whether a tumour is continuing to produce FOXM1 - and hence whether the PI3K? inhibitor is still working - would usually involve an invasive tissue biopsy. However, researchers have used a new imaging technique to monitor this in real time and non-invasively.

The technique developed and used by the team is known as hyperpolarisation. First, the team produces a form of pyruvate whose carbon atoms are slightly heavier than normal carbon atoms (they carry an additional neutron and are hence known as carbon-13 molecules). The researchers then 'hyperpolarise' - or magnetise - the carbon-13 pyruvate by cooling it to around one degree above absolute zero (-272°C) and exposing it to extremely strong magnetic fields and microwave radiation. The frozen material is then thawed and dissolved into an injectable solution.

Patients are injected with the solution and then receive a regular MRI scan. The signal strength from the hyperpolarised carbon-13 pyruvate molecules is 10,000 times stronger than that from normal pyruvate, making the molecules visible on the scan. The researchers can use the scan to see how fast pyruvate is being converted into lactate - only the continued presence of FOXM1 would allow this to happen, and this would be a sign that the drugs are not working properly.

Dr Ros added: "We've been able to detect the presence of FOXM1, our biomarker, by using this new imaging technique in breast cancer models to look for a proxy - that is, how quickly pyruvate is converted to lactate."

Professor Kevin Brindle, senior author of the study, commented: "In the future, this could provide us with a rapid assessment of how a breast cancer patient is responding to treatment without the need for invasive biopsies. This information could help put an end to giving treatments that are not working and the side effects that accompany them. Currently, patients can wait a long time to find out if a treatment is working. This technique could shorten this time, and help to tailor treatment for individual patients."

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University of Cambridge

Consuming sugary beverages while breastfeeding affects cognitive development in children

A diet high in sugar during adulthood is associated with weight gain, and has also been linked to risk of type 2 diabetes, fatty liver disease, and heart disease. New research shows that when consumed by moms during the breastfeeding period, a high sugar diet can also impact developmental outcomes during infancy.

Michael I. Goran, PhD, Program Director for Diabetes and Obesity at Children's Hospital Los Angeles, has studied how sugar can impact family health. His previous research has shown that moms who consume sugary beverages and juices in the months after giving birth are at risk for weight gain, and may also expose their newborns to these added sugars through breast milk. A new study published in The American Journal of Clinical Nutrition reveals that consuming these beverages during the breastfeeding period may also lead to poorer cognitive development in children nearly two years later.

The participants were 88 mothers who reported sugary beverages and juices consumed per day during the first month of breastfeeding. Their children were assessed using the Bayley-III Scales of Infant Development at 2 years old. Moms who reported greater consumption of sugary beverages and juices had children with poorer cognitive development scores. The researchers speculated that added sugar from the mom's diet was passed to their infant through breast milk, and this exposure could conceivably interfere with brain development.

"Breastfeeding can have so many benefits," says Dr. Goran, "but we're seeing that breast milk is influenced by what moms eat and drink even more than we realized." He says that limiting added sugars, found in beverages such as soft drinks, may have benefits not only for moms, but also for babies. "Moms may not realize that what they eat and drink during breastfeeding may influence their infant's development down the road, but that's what our results indicate."

"Ultimately, we want babies to receive the best quality nutrition," says Paige K. Berger, PhD, RD, Postdoctoral Research Fellow and first author of the study. "Our findings may be used to guide future nutrition recommendations for moms during breastfeeding, to better ensure that babies are getting the right building blocks for cognitive development."

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Children's Hospital Los Angeles

Previous infection with other types of coronaviruses may lessen severity of COVID-19

(Boston) - Being previously infected with a coronaviruses that cause the "common cold" may decrease the severity of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infections, according to results of a new study. Led by researchers at Boston Medical Center and Boston University School of Medicine, the study also demonstrates that the immunity built up from previous non-SARS-CoV-2 coronavirus infections does not prevent individuals from getting COVID-19. Published in the Journal of Clinical Investigation, the findings provide important insight into the immune response against SARS-CoV-2, which could have significant implications on COVID-19 vaccine development.

The COVID-19 pandemic has led to more than 200,000 deaths in the US, and more than one million globally. There is a growing body of research looking into specific ways that the SARS-CoV-2 virus impacts different populations, including why some people are infected and are asymptomatic, as well as what increases ones mortality as a result of infection. There are a number of vaccines under development in order to determine what type of vaccine (mRNA, viral vector) will be most effective at preventing SARS-CoV-2 infections.

While SARS-CoV-2 is a relatively new pathogen, there are many other types of coronaviruses that are endemic in humans and can cause the "common cold" and pneumonia. These coronaviruses share some genetic sequences with SARS-CoV-2, and the immune responses from these coronaviruses can cross-react against SARS-CoV-2.

In this study, the researchers looked at electronic medical record data from individuals who had a respiratory panel test (CRP-PCR) result between May 18, 2015 and March 11, 2020. The CRP-PCR detects diverse respiratory pathogens including the endemic "common cold" coronaviruses. They also examined data from individuals who were tested for SARS-CoV-2 between March 12, 2020 and June 12, 2020. After adjusting for age, gender, body mass index, and diabetes mellitus diagnosis, COVID-19 hospitalized patients who had a previous positive CRP-PCR test result for a coronoavirus had significantly lower odds of being admitted to the intensive care unit (ICU), and lower trending odds of requiring mechanical ventilation during COVID. The probability of survival was also significantly higher in COVID-19 hospitalized patients with a previous positive test result for a "common cold" coronoavirus. However, a previous positive test result for a coronavirus did not prevent someone from getting infected with SARS-CoV-2.

"Our results show that people with evidence of a previous infection from a "common cold" coronavirus have less severe COVID-19 symptoms," said Manish Sagar, MD, an infectious diseases physician and researcher at Boston Medical Center, associate professor of medicine and microbiology at Boston University School of Medicine and the study's co-corresponding author. Another interesting finding, the authors note, is that immunity may prevent disease (COVID-19) in ways that are different from preventing infection by SARS-CoV-2. This is demonstrated by the fact that the patient groups had similar likelihoods of infection but differing likelihoods of ending up in the ICU or dying.

"People are routinely infected with coronaviruses that are different from SARS-CoV-2, and these study results could help identify patients at lower and greater risk of developing complications after being infected with SARS-CoV-2," said Joseph Mizgerd, ScD, professor of medicine, microbiology, and biochemistry at Boston University School of Medicine who is the study's co-corresponding author. "We hope that this study can be the springboard for identifying the types of immune responses for not necessarily preventing SARS-CoV-2 infection but rather limiting the damage from COVID-19."

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Boston Medical Center

Donors more likely to give to COVID causes when font matches message

COLUMBUS, Ohio - Appeals seeking donations to help fight hunger during the COVID-19 pandemic were more successful when the typeface in which the appeal was written mirrored the tone of the donation request, a new study has found.

In a study that asked prospective donors to consider whether and how much to give to a local food bank to help fight hunger during the coronavirus pandemic, researchers found that donors were more likely to give when heartfelt messages were written in typefaces that looked like handwriting, and when messages that talked about the power of an organization were written in typeface that looked more business-like.

In other words, make the font match the message to get more donations, the researchers said.

"Our research suggests that simply changing the typeface of appeals messages could make those appeals stronger and encourage people to make donations," said Huiling Huang, a consumer sciences doctoral student at The Ohio State University and lead author of the study, which was published last month in the International Journal of Contemporary Hospitality Management.

When the message was a warm one, with a tone that played up the emotions of what the fundraising organization could do, donors were more likely to give when the message was written in font that looked like handwriting.

When the message was focused on the competency of the organization, on its efficiency and on its power, donors were more likely to give when the message was written in a font that was clearly generated by a computer -- much like the font you're reading now.

Previous research in this area has found that donation requests that utilize warmth-focused messages emphasize friendliness, care and love -- characteristics that convey good intentions and a desire to help others. Donation requests that focus on an organization's capabilities, efficiency and effectiveness, on the other hand, convey that organization's ability to achieve a goal. Both are effective fundraising techniques, but this new study indicates that those appeals can be even more effective if paired with the appropriate typeface.

Huang said previous analyses have shown that most donation appeals are printed in a business-like font. Depending on the message, she said, those organizations might be leaving donations on the table.

For this study, researchers asked study participants to imagine that they were picking up takeout from a local restaurant, and that, in the drive-through line, there was a flyer stating that the restaurant had partnered with a local food bank to collect donations to offset the pressures the food bank faced because of the pandemic.

Researchers offered the "prospective donors" two sets of requests for donations. One set's message focused on the strength and competence of the organization. The other's message focused on warmth and the organization's ability to positively affect lives. Each was written in two different typefaces: One that looked similar to a person's handwriting, and one that was clearly computer-generated.

Then, the researchers asked the study participants how likely they were to make a donation. They also asked questions about how deeply the participants trusted and would be loyal to the hypothetical restaurant, based only on the donation appeal.

They found that study participants were more likely to give, by a factor of about one-sixth, when the message matched the typeface -- warm messages with handwritten font, competence-based messages with computer-generated font.

Study participants also reported feeling more trust toward the restaurant asking for donations when the typeface matched the tone of the appeal. The researchers measured trust because many businesses have turned to raising money or awareness for social causes -- what researchers call "Corporate Social Responsibility (CSR)" marketing -- to build loyalty in their brands.

Studies have shown that consumer trust in a business is related to loyalty.

"We focused on a restaurant for this study, but I think our findings can be applied to a broader context way beyond restaurants and hospitality," said Stephanie Liu, senior author on the paper and an assistant professor of hospitality management at Ohio State.

"A lot of companies are using social responsibility messaging to enhance customer loyalty, and brands who solicit any types of donation can benefit from these findings. By matching the message to the font, they can build trust, which leads to loyalty."

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Ohio State University

COVID-score: A tool to evaluate public perception of countries' response to the pandemic

The Barcelona Institute for Global Health (ISGlobal), a center supported by the "la Caixa" Foundation, in coordination with the City University of New York Graduate School of Public Health & Health Policy (CUNY SPH) and other international institutions, has developed an easy and reliable tool to evaluate the public perception of governmental response to the COVID-19 pandemic.

According to an analysis of the first results obtained across 19 countries, the COVID-SCORE questionnaire can help public health officials and other decision makers identify and correct weaknesses in key aspects of a country's response, and track trends as the pandemic evolves.

Government response to the COVID-19 pandemic has varied considerably between countries. Although most governments have implemented a series of common measures such as mobility restrictions, closure of businesses, places of worship and schools, or shelter-at-home orders, the timing and approach have differed. One key element that determines the course of a pandemic is a society's compliance with such measures, which in turn depends on several factors such as trust in government or the clarity of the information that government sources provide.

"We need basic tools to help us assess the public perception of government responses in key aspects such as communication, or access to health services and social welfare," says Jeffrey V Lazarus, researcher at ISGlobal. Together with international colleagues, Lazarus coordinated the development of COVID-SCORE with 10 items related to key aspects of the government response, to be rated by the interviewees.

The study Lazarus and his colleagues published in PLOS ONE validates the tool and presents the first results from a survey conducted in June 2020 with over 13,400 participants from 19 countries heavily affected by the pandemic. The average score varied considerably between countries - from 35.76 out of a maximum of 100 for Ecuador to 80.48 for China, the country whose response was rated most positively. Countries in Asia tended to have higher scores, while Latin-American and European countries were among those with lowest scores.

As expected, the average score for a country was strongly associated with the level of trust in government, as reported in this survey and measured independently by the Wellcome Global Monitor.

"We know that public compliance with preventive measures greatly depends on the trust in public health experts, health systems and science," says Ayman El-Mohandes, Dean of CUNY SPH. Higher COVID-19 mortality or a greater percentage of respondents directly affected by the disease correlated with a lower score for the country, the researchers found.

The average score for the United States, with 773 respondents, was 50.57. Highest rated (3.16 out of 5) was the government's assistance with income, food, and shelter during the pandemic: this finding corresponds with the timing of the survey, which took place soon after initial emergency funds were distributed last spring. Notably, the US ranked seventeenth among the 19 countries surveyed with regard to government cooperation with other countries and international organisations such as the WHO (3.03 out of 5).

Spain, with 748 respondents, obtained an average score of 44.68. The highest-rated item was relative to the government's cooperation with other countries and international organisations such as the WHO (3.46 on a 1 to 5 scale), while the lowest-rated item was access to free and reliable COVID-19 testing in case of symptoms (2.09).

In all countries, questions about protection and assistance to vulnerable groups and help in meeting daily needs for income, food and shelter rated poorly, which underscores the need to give particular attention to the most vulnerable. Provision of mental health services was the lowest-rated item across all countries.

"This tool is easy to implement and can guide researchers and authorities in designing measures to better control the pandemic," says El-Mohandes. In addition, it can be done at different moments to assess the response as the pandemic evolves.

Average Score by Country

China 80.48

South Korea 74.54

South Africa 64.62

India 63.88

Germany 61.32

Canada 61.00

Singapore 57.55

Italy 51.71

United States 50.57

France 49.20

Russia 48.85

United Kingdom 48.66

Mexico 46.48

Nigeria 46.32

Spain 44.68

Sweden 42.07

Poland 41.28

Brazil 36.35

Ecuador 35.76

Credit: 
CUNY Graduate School of Public Health and Health Policy

Discovery holds potential for reversing vision loss

image: OMRF scientist Courtney Griffin, Ph.D.

Image: 
OMRF

An Oklahoma Medical Research Foundation discovery could pave the way for therapies to reverse vision loss common in premature infants and adults.

In a new study appearing in the Proceedings of the National Academy of Sciences, OMRF scientists have identified a compound that could give birth to therapies for a host of eye diseases that include retinopathy of prematurity and diabetic retinopathy.

"Potentially, even patients with advanced disease progression could see their fortunes turned around," said Courtney Griffin, Ph.D., the senior author of the study.

Several eye disorders occur when blood vessels grow out of control in the retina, the tissue that lines the back of the eye. In these forms of retinopathy, a web of vessels blocks light from reaching the retina, which is how we see. The overgrowth causes vision issues that can advance to total blindness.

Retinopathy in premature babies -- linked to high oxygen levels in NICU incubators that interrupts normal vessel development in the eye -- often resolves naturally over time. But not always. In those cases, and in adult diseases like diabetic retinopathy, vision damage can be irreversible.

Griffin and Chris Schafer, Ph.D., study the development of blood vessels. Schafer, a postdoctoral researcher, thought there might be clues to thinning this tangle of vessels if they analyzed a different set of vessels that naturally regress and disappear in mice soon after birth.

When they studied newborn mice, the OMRF researchers found that levels of a specific class of cellular proteins crashed as the mice experienced normal blood vessel loss in the eye.

"Dr. Schafer hypothesized that these cellular proteins might be an important 'off switch' to eliminate these vessels in a neonatal model," said Griffin, who holds the Scott Zarrow Chair in Biomedical Research at OMRF. "This is a new way of approaching these diseases. The current methods -- invasive surgeries or life-long injections into the eye -- only prevent the disease from advancing and often have serious complications."

Schafer identified an experimental compound that disables the proteins. It allowed him to flip the switch and test the idea.

"We wanted to trick blood vessels in diseased mice into thinking they were supposed to be regressing and naturally dying off," said Schafer. "This appears to be what happened."

Even more encouraging, Griffin said, the compound only impacted abnormal blood vessels with slow blood flow. The normal vessels needed in a healthy eye were spared.

The findings open the door to tailored therapies to reverse vision loss. It may also have implications in shrinking tumors that contain abnormal blood vessels in other parts of the body.

"We've shown that once these abnormal vessels have formed in the young eye, they're susceptible to being treated," said Griffin. The research team will now study the compound in models of adult eye diseases.

"More research is needed, but this could be a major advance in treatment for vision loss in patients of all ages," Griffin said.

Credit: 
Oklahoma Medical Research Foundation

Women more likely to embrace behaviors aimed at preventing the spread of COVID-19

Women are more likely than are men to follow guidelines outlined by medical experts to prevent the spread of COVID-19, new research finds.

In an article published in Behavioral Science & Policy, New York University and Yale University researchers report that women have practiced preventive practices of physical distancing, mask wearing, and maintaining hygiene to a greater degree than men. Women were also more likely to listen to experts and exhibit alarm and anxiety in response to COVID-19.

The findings are consistent with pre-pandemic health-care behaviors, the study's authors note.

"Previous research before the pandemic shows that women had been visiting doctors more frequently in their daily lives and following their recommendations more so than men," explains Irmak Olcaysoy Okten, a postdoctoral researcher in NYU's Department of Psychology and the paper's lead author. "They also pay more attention to the health-related needs of others. So it's not surprising that these tendencies would translate into greater efforts on behalf of women to prevent the spread of the pandemic."

The study's authors, who also included Anton Gollwitzer, a researcher at Yale University, and Gabriele Oettingen, a professor in NYU's Department of Psychology, compared women and men in endorsing preventive health practices during the peak period of the pandemic in the U.S.

The researchers' conclusions are based on three studies that employed various methodologies: a survey, on-the-street observations in different sites, and a county-level analysis of movement through GPS data from approximately 15 million smart-phone coordinates.

In the survey, researchers queried nearly 800 U.S. residents using Prolific--a research platform where individuals are compensated to complete short tasks. Questions asked about respondents' tendency to keep social distance and to stay at home (excluding shopping), frequency of hand washing, number of days of in-person contact with family or friends, and number of days of in-person contact with others.

In all their responses, women were more likely than were men to report following these practices; in all but one of these (in-person contact with others), the differences were statistically significant.

The survey also asked about which sources of information the respondents relied on for one particular behavior--social distancing. Notably, women were significantly more likely than men to rely on the following sources when deciding to what extent they distance themselves physically from others: medical experts, other countries' experiences, their governor, and social media.

In addition, women were much more likely then were men to attribute their behaviors to feeling anxious about the pandemic and their own health history as well as to feeling a responsibility to both themselves and to others.

In a second study, researchers observed a total of 300 pedestrians in three different U.S. locations by zip code (New York City/10012, New Haven, Conn./06511, and New Brunswick, NJ/08901) and tallied proper mask-wearing by covering the mouth and nose. They found a greater, and statistically significant, proportion of mask wearing among women (57.7 percent) than men (42.3 percent)--even though the gender distribution living in these zip codes was roughly equal.

In a final study, researchers compared overall movement as well as visits by men and women to nonessential retailers across U.S. counties. Nonessential retailers included restaurants, spas, fitness facilities, and florists, among others.

To do this, they analyzed aggregated GPS location data from approximately 3,000 U.S. counties and 15 million GPS smart-phone coordinates between March 9 and May 29. These numbers were obtained from Unacast, a company that collects mobility data from adults who have provided their consent. The researchers also took into account the fact that social distancing policies were instituted around mid-March and loosened toward the middle and end of April; as a result, social distancing increased and then decreased over time across these counties.

The results showed that tracked individuals in counties with a higher percentage of males showed comparatively less social distancing as the COVID-19 pandemic progressed between March 9 and May 29, as measured both by movement and by visits to nonessential retailers. In this analysis, the researchers considered the tracked sample as representative of a county's overall gender break-down.

These differences remained even after accounting for COVID-19 cases per capita in these counties, the presence of stay-at-home orders, and other demographic characteristics of the counties, such as income, education, and profession.

The authors acknowledge that the findings could have been driven by men and women holding jobs that differ--specifically, men could be more likely to hold jobs in certain sectors deemed essential and therefore exhibit greater movement. However, taking into account counties' percentages of employment in various types of professions did not alter the differences in behavior between genders. Specifically, the results were unchanged when they controlled for counties' percentage of workers in a long list of job areas--agriculture, mining, utilities, construction, manufacturing, wholesale trade, retail trade, health care and social assistance, and hospitality and food services, among others.

The researchers also considered the possible impact of political orientation. Notably, however, the effect of gender distribution on reduced physical distancing over time did not substantially decrease when they accounted for counties' percentage of votes for Donald Trump over Hillary Clinton in 2016.

"Fine-tuning health messages to alert men in particular to the critical role of maintaining social distancing, hygiene, and mask wearing may be an effective strategy in reducing the spread of the virus," says Olcaysoy Okten.

Credit: 
New York University

Letter from leading researchers urges terminology update, shift in COVID-19 guidance

Scientists affiliated with leading research institutions across the U.S. state in a letter published Monday in the journal Science that researchers across disciplines must converge to deliver clear public health guidance about how SARS-CoV-2 is spread in the air.

The researchers write in the open letter that the scientific community must clarify the terminology used related to aerosols and droplets, and employ a more modern size threshold, rather than the existing one based on 1930s-era work. Authors include experts from the University of California San Diego, University of Maryland, Virginia Tech, and others.

Public health officials should make a clear distinction between droplets ejected by coughing or sneezing - which have inspired the social distancing mantra of six feet of separation between people - and aerosols that can carry the virus for much greater distances. Viruses in aerosols smaller than 100 microns can remain airborne in a confined space for prolonged periods of time, and accumulate in poorly ventilated air, leading to transmission.

"The balance of attention must be shifted to protecting against airborne transmission," said the group, led by Kimberly Prather, Director of the National Science Foundation-funded Center for Aerosol Impacts on Chemistry of the Environment based at Scripps Institution of Oceanography at UC San Diego.

"Viruses in aerosols can remain suspended in air for many seconds to hours, like smoke, and be inhaled," according to the letter. "They are highly concentrated near an infected person, so they can infect people most easily in close proximity. But aerosols containing infectious virus can also travel more than [two meters] and accumulate in poorly ventilated indoor air, leading to superspreading events."

In addition to mask wearing, social distancing and hygiene efforts, the researchers urge for public health officials to articulate the importance of moving activities outdoors, improving indoor air using ventilation and filtration, and improving protection for high risk workers.

"The goal of this letter is to make it clear that the SARS-Cov-2 virus travels in the air and people can become infected via inhalation," said Prather, a distinguished professor who holds a joint appointment between UC San Diego's Scripps Institution of Oceanography and its Department of Chemistry and Biochemistry. "It is important to acknowledge this pathway so efforts can focus on cleaning the air and providing guidance on how to avoid risky indoor settings."

Co-author Linsey Marr, the Charles P. Lunsford Professor of Civil and Environmental Engineering at Virginia Tech and an expert on airborne transmission of viruses, added, “It is important for people to wear masks at all times in public buildings and confined spaces, not only when we can’t maintain social distance. This isn’t just an academic question, but a point that will help reduce transmission if public health officials offer clear and forceful guidance about this.”

Credit: 
University of California - San Diego

Millimetre-precision drug delivery to the brain

Researchers at ETH Zurich have developed a method for concentrating and releasing drugs in the brain with pinpoint accuracy. This could make it possible in the future to deliver psychiatric and cancer drugs and other medications only to those regions of the brain where this is medically desirable.

Today, this is practically impossible - drugs travelling through the bloodstream reach the entire brain and body, which in some cases causes side effects. The new method is non-invasive, with precise drug delivery in the brain controlled from outside the head using ultrasound. Mehmet Fatih Yanik, Professor of Neurotechnology, and his team of scientists have published their findings in the journal Nature Communications.

In order to prevent a drug from acting on the entire brain and body, the new method involves special drug carriers that wrap the drugs in spherical lipid vesicles attached to gas-containing ultrasound-?sensitive microbubbles. These are injected into the bloodstream, which transports them to the brain. Next, the scientists use focused ultrasound waves in a two-?stage process. Focused ultrasound is already employed in oncology to destroy cancer tissue at precisely defined points in the body. In the new invention, however, the scientists work with much lower energy levels, which do not damage the tissue.

Trapping drugs with sound waves

In the first step, the scientists use low energy ultrasound waves to cause the drug carriers to aggregate at the desired site within the brain. "What we're doing is using pulses of ultrasound essentially to create a virtual cage from sound waves around the desired site. As the blood circulates, it flushes the drug carriers through the whole brain. But the ones that enter the cage can't get back out," Yanik explains.

In the second step, the researchers use a higher level of ultrasound energy to get the drug carriers to vibrate at this site. Shear forces destroy the lipid membranes around the drugs, releasing the drugs to be absorbed by the nerve tissue present at the site.

The researchers have demonstrated the effectiveness of the new method in experiments on rats. First they encapsulated a neuro-?inhibitory drug in the drug carriers. Then, using the new technique, they successfully blocked a specific neural network connecting two areas of the brain. The scientists were able to show in the experiments that only this one particular part of the neuronal network was blocked and that the drug did not act on the entire brain.

More efficient drug delivery

"Because our method aggregates drugs at the site in the brain where their effect is desired, we don't need nearly as high a dose," Yanik says. In their experiments on rats, for instance, the quantity of drug that they used was 1,300 times smaller than the typical dose needed.

Other research groups have already tried to use focused ultrasound to enhance delivery of drugs to specific regions of the brain. However, these approaches couldn't trap and concentrate drugs locally, and they instead relied on causing local damage to the blood vessel cells in order to increase the drug transport from the blood to the nerve tissue with potentially long-?term detrimental consequences. "In our approach, the physiological barrier between the bloodstream and nervous tissue remains intact," Yanik says.

The scientists are currently testing the effectiveness of their method in animal models of mental illness, for example to reduce anxiety, of neurological disorders and to target lethal brain tumours that are surgically inaccessible. Once its effectiveness and advantages have been confirmed in animals will researchers be able to advance application of the method to alleviate suffering in humans.

Credit: 
ETH Zurich

Promising breath-test for cancer

image: Flinders University cancer researcher Dr. Roger Yazbek.

Image: 
Flinders University

The global quest to use a person's breath analysis for rapid, inexpensive and accurate early-stage testing for cancer and other diseases has taken a leap forward.

In a new paper in the British Journal of Cancer, Flinders University researchers have reported significant progress in developing a method to test exhaled breath profiles which accurately differentiate head and neck cancer from non-cancer patients.

The Australian researchers collected breath samples from 181 patients suspected of having early-stage head and neck squamous cell carcinoma (HNSCC) before any treatment began.

"We sought to determine the diagnostic accuracy of breath analysis as a non-invasive test for detecting head and neck cancer, which in time may result in a simple method to improve treatment outcomes and patient morbidity," says lead researchers Dr Roger Yazbek and Associate Professor Eng Ooi.

Worldwide, head and neck cancer accounts for 6% of all cancers, killing more than 300,000 people per year globally. Tobacco, alcohol and poor oral hygiene are known major risk factors for this cancer.

A surge in human papilloma virus (HPV)-associated head and neck cancers is seeing these cancers affecting a much younger population, the researchers say.

Current therapies are effective at treating early-stage disease, however late-stage presentations are common, and often associated with poor prognosis and high treatment-related morbidity.

In the Australian study, a selected ion flow-tube mass spectrometer was used to analyse breath for volatile organic compounds. Using statistical modelling, the Flinders researchers were able to develop a breath test that could differentiate cancer and control (benign disease) patients, with an average sensitivity and specificity of 85%.

Diagnosis was confirmed by analysis of tissue biopsies.

"With these strong results, we hope to trial the method in primary care settings, such as GP clinics, to further develop its use in early-stage screening for HNSCC in the community," says co-lead author Dr Nuwan Dharmawardana.

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Flinders University

New method for in utero 4D imaging of baby hearts may aid diagnosis of congenital heart disease

Researchers at King's College London have developed a new method for helping detect congenital heart disease of a baby in pregnant mothers using MRI. Existing in-utero approaches are compromised by fetal motion, but the novel method corrects the motion to present 4D visualizations of the heart depicting major vessels and blood flow circulation. With further development, the method could become a new tool for aiding diagnosis of congenital heart disease where conventional methods like ultrasound might fail.

For the first time, in a new paper published today in Nature Communications, researchers have been able to look at the fetal heart in four dimensions - the images are still 3D but change through time as the heart beats. Rather than just getting a snapshot of the heart, say a single picture, a series of images is taken allowing cardiologists to see the heart contracting and beating.

While this is standard for adult imaging, until now it has not been possible for the fetal heart because of the spontaneous movement of the baby and the rapid speed of its beating heart - twice as fast as an adult's.
Researcher Dr Tom Roberts, from King's College London, said the 4D volumes are achieved by stitching them together using mathematical motion-correction techniques and models.

"The results in the paper are exciting because no one has been able to look at the fetal heart using MRI in four dimensions like this," he said. "When we give these videos of the beating heart to the doctors, they are able to interact and examine the direction of blood flow instantly."

"The heart is a pump. Our method is very beneficial because doctors can start to measure how much blood is pumped out with each heartbeat, which can be used to tell how effectively the heart is performing. We can measure the amount of blood going through the aorta and other major vessels, simultaneously. We can get new types of measurements that you weren't able to do before in fetal MRI."

Currently diagnosis of congenital heart disease (CHD) mainly focuses on whether the fetal heart has formed in an incorrect way, but with this new technology the researchers hope to measure how well the heart is performing as well.

CHD has a broad range of different pathologies. This means sometimes there are relatively straight forward heart diseases but there are also more complicated ones which can be quite difficult to diagnose with ultrasound which currently is the main tool used.

The challenge is that while fetal blood flow can be measured using ultrasound, the measurements can often be unreliable.
MRI measurements of blood flow are easily performed in adult hearts to help tell if the heart is beating efficiently or not, or whether a vessel might have some abnormal flow of blood.
"When we scan a fetus, it moves and wriggles around however it wants which can prevent you from measuring the blood flow in the tiny vessels," Dr Roberts said.
"In our work, we've developed methods to correct for this motion and build those 3D movies where we can measure blood flow in any region or vessel of the fetal heart."

"The great thing about MRI is that it can offer really detailed, high resolution images of the fetal heart. We can use MRI for looking at the tiny vessels in the fetal heart which may be no more than 5mm wide."
Dr Tom Roberts said the team hopes the research will lead to improved care for babies born with congenital heart disease.

"If CHD is detected prior to birth, then doctors can prepare appropriate care immediately at birth, which can sometimes be life-saving. It also gives parents advance time to prepare, when otherwise the CHD might have been discovered at birth, which can be very stressful," he said.
"We are trying to advance fetal cardiac MRI as a way of potentially improving outcomes in congenital heart disease, either by being able to offer a better diagnosis or being able to look for congenital heart disease at an earlier time during pregnancy."

Second author and clinical senior lecturer in paediatric cardiology Kuberan Pushparajah said the clinical teams are very excited by the opportunities this will bring as this world leading innovation in fetal 4D imaging is applied into clinic.
"The technical challenges that have been overcome by the team in this work represent a massive leap forward in the field of fetal cardiac MRI," he said.
"We will now be able to simultaneously study the heart structures and track blood flow through it as it beats using MRI for the very first time."

"This is key in the assessment of congenital heart disease where the heart structures and connections are abnormal and can be very complex. This will help us better understand and diagnose congenital heart disease to improve patient care."

Credit: 
King's College London