Body

Patients who received a transplanted liver infected with hepatitis C and were later treated for the infection performed as well in recovery as transplant patients who received an organ free of infection, according to study from the University of Cincinnati College of Medicine and UC Health recently published in the journal Liver Transplantation.

Two sets of 32 patients were enrolled in groups: one group receiving livers for transplant from donors testing positive for hepatitis C (HCV) and a second receiving livers for transplant from donors testing negative for the infection. One patient in the experimental group died as a result of factors not related to hepatitis C during transplantation.

"What we found is that you can use hepatitis C infected livers and the results in this interim analysis are the same whether there is a need to treat organs affected by hepatitis C or not," explains Shimul Shah, MD, professor of surgery in the UC College of Medicine, the James and Catherine Orr Endowed Chair of Liver Transplantation, section chief of transplantation at UC Health and senior author of the study. "Everyone who received a liver affected by hepatitis C was cleared of the virus."

As part of the clinical trial, 32 patients received HCV-positive livers while a control group of 32 patients, all at University of Cincinnati Medical Center, received non infected livers for transplantation between June 2018 and October 2019. No HCV treatment failures were reported and there were no differences in 30-day and one-year graft (or organ) and patient survival, length of hospital stay, complications or blood infections between the two groups.

"HCV-positive organs can be safely used in patients who do not have the infection, and HCV can be safely eradicated, thereby increasing the chances for the patients to receive vital organ transplants," said Nadeem Anwar, a professor in the UC Department of Internal Medicine, a UC Health physician and first author of the scholarly journal.

"There is a big difference between the demand and supply of livers and previously organs affected with hepatitis C were being discarded," said Anwar. "With this study it is clear that we can help more patients get transplanted using HCV-positive organs."

"With the opioid crisis, unfortunately, there have been more overdose-related deaths and some of these patients do donate organs," said Anwar. "Some of these organs may be hep C-positive, but since the donors are young, the livers are still in very good condition and can be used for transplants."

Nationally, there are 13,000 patients waiting for liver transplants. In 2019, 133 liver transplants were performed at UC Medical Center, said Shah.

"This is the largest study of liver transplantation published in North America," said Shah. "This is the first one published for liver transplant patients proving you can do this safely and that's why we wanted to get it out there."

The median age for individuals receiving a HCV-positive liver in the study was 60, while for the control group the media age was 57. Median donor age was 37. Most of the participants in both groups were white males. Individuals needing treatment for hepatitis C received it 47 days after transplantation.

Shah said physicians wanted to make sure there were no complications from the liver transplant and they also needed to wait for insurance companies to cover the cost of hepatitis C medications, which typically consists of a 12-week regimen of an HCV protease inhibitor.

"With the excellent results that we demonstrated in this study, we have made this a standard of care at UC Medical Center to offer these organs to our patients," said Anwar.

DALLAS - June 22, 2020 - For decades, high-density lipoprotein (HDL) cholesterol has been dubbed "good cholesterol" because of its role in moving fats and other cholesterol molecules out of artery walls. People with higher HDL cholesterol levels tend to have lower rates of cardiovascular disease, studies have shown.

Now, UT Southwestern scientists have analyzed data on more than 15,000 people to better understand the association between HDL cholesterol, heart attacks, and strokes in diverse populations. They found that the number of HDL particles, a little-used measurement of HDL, is a more reliable predictor of heart attack and stroke risk than the standard HDL cholesterol metric. Moreover, they found that among black people, neither HDL measurement was significantly associated with heart attack.

"Previous studies have looked at HDL levels in the population as a whole," says Anand Rohatgi, M.D., an associate professor of internal medicine at UTSW. "But we know that sometimes biology differs by gender and race, so we thought it was important to separately tease apart what's happening in those populations, as well as how HDL is associated with stroke, which has been understudied."

According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death in the U.S. More than 12 percent of adults in the U.S. have high total cholesterol levels, and more than 18 percent have what's currently considered low levels of HDL cholesterol.

Cholesterol is a waxy substance that is used by the body to make hormones and keep cells functioning properly. But when low-density lipoprotein (LDL) cholesterol levels are too high, cholesterol can accumulate inside blood vessels, forming deposits called plaques. These plaques can eventually lead to blood vessel blockages that cause heart attacks or strokes. HDL cholesterol helps remove cholesterol from blood vessels. But recent studies have come to mixed conclusions about the association between HDL cholesterol levels and health outcomes.

For the new paper, published in the journal Circulation, Rohatgi and his colleagues pooled together information on people who had participated in four large, nationwide studies - the Dallas Heart Study, Atherosclerosis Risk in Communities study, Multi-Ethnic Study of Atherosclerosis, and the Prevention of Renal and Vascular Endstage Disease study. In all, the studies included 15,784 people followed over an average of 8 to 12 years. Of the participants, 54 percent were male, 22 percent were black, and their average age was 56 years.

"By combining all these large existing cohorts, we had enough numbers to look at these populations that had been understudied in the past," says Kavisha Singh, M.D., a research fellow in cardiology at UTSW and first author of the new study.

In addition, the data included two different measurements of HDL: HDL-P levels tally how many particles of HDL are circulating in the blood. HDL-C levels, the standard test, instead quantify how much total HDL cholesterol is inside those particles. Since the number of HDL particles may vary with regards to how much cholesterol they contain, the two measurements can be quite different and are only moderately correlated.

In the study, people with the highest HDL-P levels, above 37 mmol/L, had a 37 percent lower risk of heart attack and a 34 percent lower risk of stroke than those who had the lowest HDL-P levels. In women, this association was stronger - those with the highest HDL-P levels had a 49 percent reduction in heart attacks and 46 percent reduction in stroke. While HDL-C predicted heart attack risk in the overall pool of people as well as in women, it was not associated with stroke.

When the researchers homed in on black participants, the results were different - neither HDL-C nor HDL-P was linked to a black person's risk of heart attack.

"If you're white, low HDL cholesterol is still a powerful predictor of heart attack and stroke risk, and that has not changed," says Rohatgi. "But if you're not white, it's not that straightforward."

A better understanding of how HDL can help predict disease, and how that association varies among populations, is vital to lowering rates of cardiovascular disease, the researchers say.

"These risk markers are really relevant in everyday primary care and cardiology," says Singh. "Doctors use cholesterol levels to make decisions like whether a patient goes on medication or not."

The team is planning future studies on the functionality of HDL particles among black people, how HDL-P may be used clinically, and whether HDL-P might be associated with specific subtypes of strokes.

Scientists at the Institute of Digital Healthcare, WMG and Warwick Medical School, at the University of Warwick, have analysed mortality statistics in the UK during the initial phases of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic, by analysing the weekly national mortality statistics over the last five years including the subgroup of respiratory mortality rates

They found there were fewer deaths recorded from the end of December 2019 until the end of March 2020 in comparison to the previous five years, including in the subgroup assessment of respiratory mortality rates

The researchers describe a SARS-CoV-2 Paradox that resulted in a lower death rate during the early stages of the pandemic in comparison to previous years, perhaps due to government enforced social distancing introduced in the middle of March.

Some had already engaged with social distancing before a formal lockdown, and precautions such as more hand washing, lead to a reduction in the mixing of those with infectious diseases including, but not exclusive of, SARS-CoV-2

An analysis of national weekly mortality rates between December 2019 - March 2020, compared to the same period for the previous five years, by researchers at WMG and WMS, University of Warwick, has shown that there have been fewer deaths registered this year during the lead up to the Covid-19 pandemic. Researchers have called this the SARS-CoV-2 Paradox - which could be due to early social distancing measures.

Researchers from the Institute of Digital Healthcare, WMG and Warwick Medical School, at the University of Warwick, have analysed the mortality statistics in the United Kingdom during the initial phases of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic to understand the impact of the pandemic on national mortality figures.

They did this by carrying out a retrospective review of weekly national mortality statistics in the United Kingdom over the previous 5 years, including subgroup assessment of respiratory mortality rates, from the end of November until the end of March.

The analysis found that during the first months of 2020, when the early phases of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic was apparent in the UK, there were consistently fewer deaths each week compared with the previous five years.

However, such a pattern has not been seen in the previous five years of data, researchers coined this the SARS-CoV-2 Paradox, and propose the reason why the death rate was lower during the early stages of the pandemic in comparison to previous years could be due to social distancing, as whilst the government enforced social distancing in the middle of March, some had already engaged with this, especially higher risk groups/elderly, leading to a reduction in the mixing of those with infectious diseases including, but not exclusive of, SARS-CoV-2.

It could also be due to the emphasised importance of washing hands, staying home when you feel unwell and coughing or sneezing into a tissue, this is likely to reduce the number of cases of other infectious disease and, also, slow the spread of various infectious diseases. Finally, iatrogenic mortality may be reduced, as hospital admission numbers have reduced; and there may thus be a reduction in the spread of hospital-acquired infections, such as methicillin-resistant staphylococcus aureus (MRSA). Similarly, reductions in elective surgery (in order to prepare intensive care and hospital bed capacity) may result in fewer iatrogenic deaths.

The graph shows week 12, the 20th March there was an increase in deaths, with 2020 deaths being 10,645, and previous 5 year mean to be 10,573, this could be related to covid-19, as symptoms such as headaches and loss of taste weren't identified, however it could also be attributed to closed GPs, an overwhelmed A&E and ITUs being increasingly selective about which patients to take as lockdown was formally announced that week.

Professor Theo Arvanitis, from the Institute of Digital Healthcare at WMG, University of Warwick comments:

"Each year, infectious diseases make a significant contribution towards avoidable deaths in England and Wales. People with multi-morbidities are at particular risk, and this is a key area of research for the Institute of Digital Healthcare. Social distancing measures are likely to impact the spread of all infectious diseases, despite their target being a reduction in the spread of SARS-CoV-2 virus. This lack of disease spread could be causing a reduction in death rate. Another factor could be concerns around the virus, which could mean people are making more conscious health decisions in terms of eating, exercise, reducing smoking and resting, when they feel unwell, or seeking advice from 111 about their symptoms.

"It is important to note that whilst we have seen a reduction in mortality in the 'run-up' to seeing the full extent of SARS-CoV-2 that this may also have negative future consequences. It is possible that we may see a significant rebound if this mortality has simply been delayed rather than avoided in its entirety. If a rebound affect is seen, this may coincide with the peak demand for SARS-CoV-2 medical beds, creating an even greater healthcare need.

"Overall, this stresses the need for careful ongoing observation and exploration of these mortality trends. This assessment must take account not just of the SARS-CoV-2 peak, but also the time period prior to, and following the pandemic."

'England and Wales Mortality Statistics: The SARS-CoV-2 Paradox' is published in the Journal of International Medical Research, DOI: 10.1177/0300060520931298

A novel formulation of the prostate cancer drug abiraterone acetate - currently marketed as Zytiga - will dramatically improve the quality of life for people suffering from prostate cancer, as pre-clinical trials by the University of South Australia show the new formulation improves the drug's effectiveness by 40 per cent.

Developed by Professor Clive Prestidge's Nanostructure and Drug Delivery research group at UniSA's Cancer Research Institute, the breakthrough discovery uses an oil-based oral formulation that not only enables a smaller dose of the drug to be effective, but also has the potential to dramatically reduce possible side effects, such as joint swelling and diarrhoea.

Despite Zytiga being the leading formulation to treat prostate cancer, lead researcher, Dr Hayley Schultz says the new formulation will ultimately provide a better treatment for patients with prostate cancer.

Prostate cancer is the most commonly diagnosed cancer in men, with one in six at risk of diagnosis before the age of 85.
In 2019, more than 19,500 cases of prostate cancer were diagnosed in Australia. Globally, prostate cancer cases reached 1.28 million in 2018.

"Many drugs are poorly water soluble, so when they're ingested, they enter the gut but don't dissolve, which means that their therapeutic effect is limited," Dr Schultz says.

"This is the case for Zytiga. Here, only 10 per cent of the dose is absorbed, leaving the other 90 per cent undissolved, where it simply passes through the body as waste.

"On top of this, patients taking Zytiga must fast for two hours prior to taking the drug, and another hour after taking the drug to achieve predictable absorption. And as you can imagine, this can be painstakingly inconvenient.

"Our new formulation changes this. By using oils to mimic pharmaceutical food effects, we're able to significantly increase the drug's solubilisation and absorption, making it more effective and a far less invasive treatment for patients."

The new formulation uses very high levels of abiraterone acetate dissolved within a specific oil and encapsulated within porous silica microparticles to form a powder that can be made into tablets or filled into capsules. Applied to human treatment, it could reduce the dose from 1000mg to 700mg per day, without the need for fasting.

Prof Prestidge says if the team can secure funding, clinical trials in humans could be just two years away.

"Based on our knowledge of this drug's pharmaceutical food effect, we hypothesise its absorption in humans will be extensively improved using this technology", Prof Prestidge says.

"Anything we can do to contribute to the development of a commercialised product to improve the lives of patients, is invaluable.

"This novel formulation is flexible enough to be adopted by thousands of different medicines; its potential to help patients of all kinds is exponential."

One in four adults in the UK are experiencing food insecurity, which is likely to have left them susceptible to hunger and potential malnutrition, during the COVID-19 pandemic. That is the main finding of a survey published today by Feeding Britain and Northumbria University's Healthy Living Lab.

The survey finds that 25% of adults have struggled during the pandemic to access food they can afford, and are likely to have been susceptible to hunger and potential malnutrition as a result. Meanwhile, nearly one in four adults looking after children have eaten less so they can feed the children in their household.

Half of all adults have tried to cope during the pandemic by purchasing less expensive food which they would not ordinarily choose to buy. That figure rises to nine in ten amongst adults who live in households that are the least food secure and most susceptible to hunger and potential malnutrition. Adults within this group are also the most likely to have used coping strategies which involve wasting less food, planning meals more carefully, and cooking main meals from scratch.

Even the high use of various coping strategies such as buying less expensive food, borrowing food, using food banks, sending children to eat elsewhere, and restricting the food they eat at a relatively high rate, has not enabled adults to become food secure and live free of hunger and potential malnutrition.

Adults who are the least food secure, and most susceptible to hunger and potential malnutrition, are also the most likely to have increased their use of coping strategies during the pandemic. Nearly one in three adults in this group, and who are looking after children, have resorted more frequently to eating less so that their children can eat, compared to only one in sixteen adults looking after children who report little or no problem in accessing the food they need.

Commenting on the findings, Andrew Forsey, Director of Feeding Britain said: "This survey reveals the lengths to which millions of people in our country are going to keep themselves and their families fed during the pandemic. It reveals also the uphill struggle that all too many of them have faced in doing so while attempting to maintain their dignity, independence, and self-sufficiency.

"During Feeding Britain's emergency food programme, through which our regional networks will have distributed a million meals by the end of June, it has become increasingly clear that a broader group of households, in addition to the very poorest, are struggling to pay the bills and still put food on the table. This survey shows, sadly, just how many of our fellow citizens are now in that group. They have been exposed to hunger and potential malnutrition by a combination of low income and isolation, which has tended to follow a loss of earnings or problems with the benefits system."

Professor Greta Defeyter, Director of Northumbria University's Healthy Living Lab, added: "These findings present an appalling picture of the high percentage of adults experiencing food insecurity in the UK. If we, as a country, are to stand a chance of getting to grips with this problem, we need the Prime Minister to oversee and implement with urgency a national food strategy which enhances the supply, affordability, and accessibility of nutritious food to everyone in our country, while minimising the need to deploy the many coping strategies, such as the use of food banks, which we have identified through this survey. These are often measures of last resort and do not compensate for an adequate income and the availability of affordable nutritious food within all communities."

On the back of the findings, Feeding Britain recommends the introduction of a jobs programme to prevent long-term unemployment, a review of deductions from Universal Credit and the suspension of the two-child limit, a seamless year-round school meals programme which includes breakfast and lunch for children, automatic registration and inflation-proofing for Healthy Start vouchers, innovation funding for community food programmes, and tougher employment protections for people in low-paid and precarious work.

Read the full report here.

Washington, DC - June 19, 2020 - Administering the MMR (measles, mumps, rubella) vaccine could serve as a preventive measure to dampen septic inflammation associated with COVID-19 infection, say a team of experts in this week's mBio, a journal of the American Society for Microbiology. Long-time collaborators and spouses Dr. Paul Fidel, Jr., Department Chair, Oral and Craniofacial Biology, and Associate Dean for Research, Louisiana State University Health School of Dentistry and Dr. Mairi Noverr Professor of Microbiology & Immunology at Tulane University School of Medicine in New Orleans co-authored the perspective article based on ideas stemming from research in their labs. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19, say the researchers.

"Live attenuated vaccines seemingly have some nonspecific benefits as well as immunity to the target pathogen. A clinical trial with MMR in high-risk populations may provide a low-risk-high-reward preventive measure in saving lives during the COVID-19 pandemic," said Dr. Fidel. "While we are conducting the clinical trials, I don't think it's going to hurt anybody to have an MMR vaccine that would protect against the measles, mumps, and rubella with this potential added benefit of helping against COVID-19."

Mounting evidence demonstrates that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing trained nonspecific innate immune cells for improved host responses against subsequent infections. Live attenuated vaccines induce nonspecific effects representing "trained innate immunity" by training leukocyte (immune system cells) precursors in the bone marrow to function more effectively against broader infectious insults.

In Dr. Noverr's laboratory, in collaboration with Dr. Fidel, vaccination with a live attenuated fungal strain-induced trained innate protection against lethal polymicrobial sepsis. The protection was mediated by long-lived myeloid-derived suppressor cells (MDSCs) previously reported inhibiting septic inflammation and mortality in several experimental models. The researchers say that an MMR vaccine should be able to induce MDSCs that can inhibit or reduce the severe lung inflammation/sepsis associated with COVID-19. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis.

Recent events provide support for the researchers' hypothesis. The milder symptoms seen in the 955 sailors on the U.S.S Roosevelt who tested positive for COVID-19 (only one hospitalization) may have been a consequence of the fact that the MMR vaccinations are given to all U.S. Navy recruits. In addition, epidemiological data suggest a correlation between people in geographical locations who routinely receive the MMR vaccine and reduced COVID-19 death rates. COVID-19 has not had a big impact on children, and the researchers hypothesize that one reason children are protected against viral infections that induce sepsis is their more recent and more frequent exposures to live attenuated vaccines that can also induce the trained suppressive MDSCs that limit inflammation and sepsis.

The researchers propose a clinical trial to test whether the MMR vaccine can protect against COVID-19, but in the meantime, they suggest that all adults, especially health care workers and individuals in nursing homes get the MMR vaccine. "If adults got the MMR as a child they likely still have some level of antibodies against measles, mumps, and rubella, but probably not the myeloid-derived suppressor cells," said Dr. Fidel. "While the MDSCs are long-lived, they are not life-long cells. So, a booster MMR would enhance the antibodies to measles, mumps, and rubella and reinitiate the MDSCs. We would hope that the MDSCs induced by the MMR would have a fairly good life-span to get through the critical time of the pandemic."

Dr. Noverr was recently awarded a "Fast Grant" (part of Emergent Ventures at the Mercatus Center, George Mason University) to test the efficacy of MMR directly in a nonhuman primate model of COVID-19 infection.

Pregnant and postpartum women are already at a high risk of depression and anxiety - one in seven women struggle with symptoms in the perinatal period. But the coronavirus pandemic is exacerbating those struggles according to a recent study published in Frontiers in Global Women's Health, which found that the likelihood of maternal depression and anxiety has substantially increased during the health crisis.

"The social and physical isolation measures that are critically needed to reduce the spread of the virus are taking a toll on the physical and mental health of many of us," says Dr. Margie Davenport of the University of Alberta, Canada, who co-authored the study.

For new moms, those stresses come with side effects. "We know that experiencing depression and anxiety during pregnancy and the postpartum period can have detrimental effects on the mental and physical health of both mother and baby that can persist for years." Such effects can include premature delivery, reduced mother-infant bonding, and developmental delays in infants.

The study surveyed 900 women - 520 of whom were pregnant and 380 of whom had given birth in the past year - and asked about their depression and anxiety symptoms before and during the pandemic. Before the pandemic began, 29% of those women experienced moderate to high anxiety symptoms, and 15% experienced depressive symptoms. During the pandemic, those numbers increased - 72% experienced anxiety and 41% experienced depression.

Because lockdown measures have affected daily routines and access to gyms, researchers also asked women whether their exercise habits had changed. Of the women surveyed, 64% reduced their physical activity since the pandemic began, while 15% increased and 21% experienced no change. Exercise is a known way to ease depression symptoms, so limited physical activity may result in an uptick in depressive symptoms. Indeed, the study found that women who engaged in at least 150 minutes of moderate physical activity a week had significantly lower symptoms of depression and anxiety.

The findings are somewhat limited given the fact that researchers could not survey women before the pandemic began (since they could not know a pandemic would occur). The women surveyed could only offer their pre-pandemic symptoms in hindsight. Also, while the researchers asked women about their symptoms using validated measures, only mental health care professionals can validly diagnose an individual with depression or anxiety.

The study was specifically interested in the impact of COVID-19 on new moms, but Davenport says maternal mental health is a critical issue no matter the time. "Even when we are not in a global pandemic, many pregnant and postpartum women frequently feel isolated whether due to being hospitalized, not having family or friends around or other reasons," she says.

"It is critical to increase awareness of the impact of social (and physical) isolation on the mental health of pregnant and postpartum women," Davenport continues. Increased awareness makes diagnosis and treatment - the ultimate goal - more likely.

A new study has found that tanezumab, a monoclonal antibody that inhibits nerve activity, provides relief in patients with chronic low back pain, one of the leading reasons why people seek medical care and the number one cause of disability worldwide.

"This demonstration of efficacy is a major breakthrough in the global search to develop non-opioid treatments for chronic pain," said John Markman, M.D., director of the Translational Pain Research Program in the University of Rochester Medical Center (URMC) Department of Neurosurgery and lead author of the study which appears in the journal Pain. "There were also improvements in function linked to the reduction in pain severity."

This is the first study that shows long-term relief for chronic low back pain with a single dose of tanezumab delivered under the skin once every two months. The study was conducted in 191 sites across eight countries in North America, Europe, and Asia.

Researchers are increasingly finding that certain proteins circulating in the bloodstream heighten the sensitivity of cells in the nervous system to pain. One of these proteins, called nerve growth factor (NGF), may explain why some individuals experience more intense and chronic back pain. Tanezumab is an NGF inhibitor.

The patients with chronic low back pain enrolled in this study did not previously have relief with at least three different types of pain medication, including opioids, and were considered "difficult-to-treat." Patients with symptoms, signs, and x-ray evidence of moderate-to-severe osteoarthritis, a disorder commonly found in older patients with chronic low back pain, were excluded from the study.

Tanezumab has not been associated with the often serious adverse side effects seen with opioids or nonsteroidal anti-inflammatory drugs (NSAIDs), which are often used to treat low back pain. However, this class of drugs has been linked to joint problems, which are sometimes serious enough to require joint replacement. Because of this concern, the researchers followed participants for an extended period and determined there was a low rate of serious joint problems requiring joint replacement.

"In the future, clinicians may have to weigh the different risks of lumbar fusion surgery, chronic opioid use, or NSAIDs against the unique risks of a rare but rapidly progressive form of joint problem associated with blocking nerve growth factor," said Markman. "I expect that that the tradeoffs between benefit and risk will be different for osteoarthritis than for chronic low back pain."

The findings - that 68 percent of Australians and 67 percent of New Zealanders surveyed are in favour - come at a critical time, with Australian and New Zealand Health and Food Ministers shortly to vote on recommendations by independent authority Food Standards Australia New Zealand (FSANZ) to introduce long-awaited alcohol warning labels.

Conducted by The George Institute for Global Health, the study measured the level of support for 14 alcohol control initiatives relating to a range of issues including alcohol labelling, pricing and promotion across seven countries - Australia, Canada, China, India, New Zealand, the United Kingdom and the United States.

As part of a larger study examining attitudes and behaviours relevant to health policy support across the seven countries a minimum of 1,000 adults (18+ years) from each country completed an online survey.

While previous research on public attitudes to alcohol policies has examined attitudes in higher-income countries, this is one of few studies to also examine support for such policies in China and India - two highly populous countries experiencing rapid economic growth and rising per capita alcohol consumption.

Across all policies, support was generally higher in India (80-86 percent) and China (57-85 percent), and lower in the United States (33-72 percent) and Canada (35-68 percent).

Support was highest for labelling requirements, in particular pregnancy warnings (67-85 percent) and standard drink quantity information (63-83 percent).

Professor Simone Pettigrew, Program Head, Food Policy at The George Institute and study co-author said the high level of public support for alcohol control initiatives in the seven countries surveyed was helpful in providing governments with the impetus they need to introduce appropriate and effective public health measures.

"More broadly speaking, I would hope that these findings can act as a conversation-starter with policymakers. Of most significance for policymakers is the strong alignment between the alcohol policy measures proven to be most effective and the preferences of Australians and the respondents surveyed in the other six countries," she said.

Professor Pettigrew added that the message for Australia's State, Territory and Commonwealth leaders regarding support for health warning labels on alcohol products could not be louder or more timely.

"I would hope that when the Food Forum Ministers meet in the coming weeks to reconsider the expert advice of FSANZ, the combined weight of an evidence-based recommendation, together with majority support from the Australian community, will lead to a positive health outcome with the introduction of clear and visible health warnings on alcohol products," Professor Pettigrew said.

What The Study Did: This study describes the characteristics associated with outpatient cardiac arrests and death during the COVID-19 pandemic in New York.

Authors: David J. Prezant, M.D., of the Fire Department of the City of New York in Brooklyn, is the corresponding author.

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

(doi:10.1001/jamacardio.2020.2488)

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

Cabbage plants defend themselves against herbivores and pathogens by deploying a defensive mechanism called the mustard oil bomb: when the plant tissue is damaged, toxic isothiocyanates are formed and can effectively fend off attackers. Researchers at the Max Planck Institute for Chemical Ecology and the University of Pretoria have now been able to show in a new study that this defense is also effective to some extent against the widespread and detrimental fungus Sclerotinia sclerotiorum. However, the pathogen uses at least two different detoxification mechanisms that enable the fungus to successfully spread on plants defended in this way. The metabolic products thus formed are non-toxic to the fungus, allowing it to grow on these plants (Nature Communications, June 2020, DOI 10.1038/s41467-020-16921-2).

Sclerotinia sclerotiorum is a devastating fungal pathogen that can infect more than 400 different plant species. The main symptom of the disease called Sclerotinia wilt or white mold is wilting. Visible are also the white, cotton-like fungal spores that overgrow plant leaves and stalks. In agriculture, rapeseed cultivation is particularly at risk. The plant disease can affect other members of the cabbage family, and also potatoes, legumes and strawberries.

Scientists at the Max Planck Institute for Chemical Ecology in Jena have long been studying the glucosinolates and isothiocyanates that constitute the special defense mechanism of cabbage family plants, which include rapeseed, radishes and mustard. "We wanted to find out how successful plant pathogens overcome the plant defense and colonize these plants. We therefore asked ourselves whether widespread fungal pathogens have strategies to adapt to the chemical defenses of plants of the cabbage family," Jingyuan Chen, the first author of the study, explains.

The researchers were able to show experimentally that the defense based on glucosinolates is actually effective against fungal attacks. However, they also discovered two different strategies of the white mold fungus to detoxify the defensive substances: The first is a general detoxification pathway that binds glutathione to the isothiocyanate toxins. This type of detoxification of organic poisons is quite common in insects and even mammals. The second and far more effective way to render the isothiocyanates harmless is to hydrolyse them, i.e. to cleave them enzymatically with a water molecule. The researchers wanted to identify the enzymes and corresponding genes underlying this detoxification mechanism. Genes that enable the successful detoxification of these substances had already been described in bacteria. They are called Sax genes after experiments with the model plant Arabidopsis thaliana: Survival in Arabidopsis eXtracts.

"We based our search on the known bacterial SaxA proteins to select candidate genes for further investigations. We then tested whether these genes are actually expressed in greater quantities in fungi exposed to the toxins, and whether the resulting protein can render the toxins harmless," explains Daniel Vassão, one of the study leaders. Using high-resolution analytical methods, the scientists were able to identify and quantify the metabolites produced by the fungus during detoxification. They also used mutants of the fungus in which the SaxA-encoding gene had been knocked out for comparison. This revealed that the Sax protein of the white mold fungus is active against a range of isothiocyanates, allowing it to colonize different plants of the cabbage family.

Mutants lacking the gene for this detoxification pathway were dramatically reduced in their capacity to tolerate isothiocyanates. "However, it was surprising to see that these mutants up-regulated their general pathway of detoxification, although this did not compensate for the mutation," says Jingyuan Chen. Glutathione conjugation cannot detoxify isothiocyanates nearly as effectively as hydrolysis can. Although it seems to be metabolically more expensive for the fungus, this general pathway is always present as it helps the fungus to detoxify a huge variety of poisons. "It is possible that this general pathway protects the fungus initially, while the machinery required for the more specialized pathway is assembled after an initial exposure to the toxin and can take over later in the infection," says Daniel Vassão.

In further experiments, the researchers want to investigate whether other fungi that successfully infect plants of the cabbage family also detoxify isothiocyanates via the same pathway, and whether unrelated fungal species are also able to degrade these toxins. "Then we will know whether this widespread detoxification is due to repeated evolution in fungi colonizing mustards, or is a feature which has been conserved over time and is therefore found in many fungal lines," Jonathan Gershenzon, director of the Department of Biochemistry where the research was conducted, concludes.

Death records point to hundreds of U.S. deaths from heat each year, but even moderately hot weather may actually be killing thousands. This summer, COVID-19 may make it harder to stay cool.

As temperatures rise this summer, a new study by Boston University School of Public Health (BUSPH) and the University of British Columbia School of Population and Public Health (UBC SPPH) researchers finds that thousands of U.S. deaths may be attributable to heat each year, far more than the 600 deaths previously estimated by the Centers for Disease Control and Prevention (CDC).

Published in the journal Environmental Epidemiology, the study estimates that heat contributed to the deaths of 5,600 people each year on average between 1997 and 2006 in 297 counties comprising three-fifths of the U.S. population.

Most of these deaths were from only moderately hot weather, rather than extremely hot weather--categories that the researchers defined not by temperature, but by what temperatures are normal for a given region of the U.S.

"How dangerous a hot day is may depend on where you live," says study lead author Dr. Kate R. Weinberger, assistant professor of occupational and environmental health at UBC SPPH.

"A 90°F day might be dangerous in Seattle, but not in Phoenix," she says. "One of the factors that gives rise to this phenomenon is differing degrees of adaptation to heat. For example, air conditioning is much more common in cities like Phoenix that experience hot weather frequently versus cities like Seattle with cooler climates," Weinberger says, noting that demographic factors can also affect how vulnerable a population is to heat--heat especially endangers older adults, children, pregnant women, and outdoor workers.

The researchers used data from the National Center for Health Statistics on deaths in the most populous counties (1997 to 2006 was the most recent decade with continuous data available), and the Parameter-elevation Relationships on Independent Slopes Model (PRISM), which estimates temperatures across the contiguous U.S. down to the four-square-kilometer area.

While most previous research has focused on the information provided on death records to try to estimate deaths from heat, this study analyzed the association between days considered moderately or extremely hot in that county and the number of deaths from any cause, showing that not hundreds but thousands of deaths are tied to heat. The researchers estimated that moderate heat killed 3,309 people per year in the counties included in the study, and extreme heat killed 2,299 people each year.

"These estimates do not depend on anyone recognizing that a given death was due to excess heat, so they are likely closer to the true number than previous estimates," says study senior author Dr. Gregory Wellenius, director of BUSPH's Climate and Health program.

"Heat is very much a threat to the health of our communities and our families today," he says. "Public health officials have a responsibility to implement heat action plans--as many communities across the world already have--in order to warn residents ahead of days of extreme heat and to help residents cope with the heat and minimize their health risks."

However, the researchers point out that COVID-19 will make it harder to stay cool this summer. "Providing publicly accessible air conditioned spaces on hot days now carries additional risks and requires new protocols for keeping people safe from both heat and infection," Wellenius says.

"At the same time, with many offices, malls, stores, restaurants, and other commercial buildings still largely closed, this summer people are even more reliant on home air conditioning than ever before," he says. "Given the high unemployment rates, particularly among vulnerable communities, we may see an even bigger impact of heat on people's health this summer."

No mass gatherings. Stay-at-home orders. Nonessential business closures. Use of cloth face coverings. In April, these and other measures were adopted by states to try to mitigate the spread of COVID-19 in the U.S. and across the globe. A new study published in the Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report presents data from a survey of Americans assessing their behaviors and attitudes about these mitigation measures. Senior author Charles A. Czeisler, MD, PhD, Chief of the Division of Sleep and Circadian Disorders at Brigham and Women's Hospital, along with colleagues from the Brigham, the CDC, Monash University, and Austin Health, analyzed results of the survey administered in May, which found widespread support for the public health measures.

"We believe that routine assessment of public attitudes, behaviors, and beliefs related to COVID-19 and its mitigation should be a priority," said Czeisler. "This is especially important given that currently, the most effective defense against transmission of COVID-19 is reducing person-to-person contact, which depends on public support and engagement."

From May 5-12, 2020, a total of 4,042 adults in the U.S. were invited to complete a web-based survey administered by Qualtrics, LLC. Participants were recruited using methods to create panels representative of the 2010 U.S. Census by age, gender, race, and ethnicity. Overall, surveys completed by 2,221 U.S. adults were analyzed. Questions in the survey focused on public attitudes, behaviors and beliefs related to stay-at-home orders, nonessential business closures and public health guidance.

Most respondents supported stay-at-home orders and nonessential business closures. Nationwide, 79.5 percent of participants supported these measures, with even greater support in New York City and Los Angeles. Respondents reported a very high level of adherence to public health recommendations designed to slow the spread of COVID-19, including usage of cloth face coverings when in public areas (74.1 percent), maintaining physical distancing (79.5 percent), and avoidance of gatherings of 10 or more people (85.9 percent).

More than 77 percent of adults reported self-isolating and 84 percent believed their state's COVID-19 community mitigation strategies were the right balance or not restrictive enough. Most respondents (74.3 percent) reported that they would feel unsafe if restrictions were lifted at the time of the survey. Since then, stay-at-home orders have been lifted in many states across the nation.

The authors note that responses to the survey are self-reported and may be subject to recall, response and social desirability biases. The survey also had a lower percentage of responses from Black people than is representative of the U.S. population.

In a preprint paper available on medRxiv, Czeisler and colleagues presented survey results from questionnaires administered from the week of April 2-8. In this survey, the team found broad support for stringent COVID-19 mitigation strategies and widespread concern about the possibility of an economic recession (79.2 percent) and open-endedness of the pandemic (72.2 percent). They found that nearly 4-out-of-5 Americans reported disruptions to their social lives, 4-in-10 reported disruption to work, sleep, family life, productivity and physical activity, and 1-in-5 reported disruption of sexual activity associated with the pandemic and its mitigation. Both surveys suggest that despite these concerns, Americans widely maintained their strong support for community mitigation strategies and public health recommendations in May.

"These findings suggest that Americans have prioritized their health amid the pandemic, notwithstanding considerable adverse economic, social and health consequences," said Czeisler.

A report from Ann & Robert H. Lurie Children's Hospital of Chicago shows that infants under 90 days of age who tested positive for COVID-19 tend to be well, with little or no respiratory involvement. Fever was often found to be the primary or only symptom. Findings were published in The Journal of Pediatrics.

"While there is limited data on infants with COVID-19 from the United States, our findings suggest that these babies mostly have mild illness and may not be at higher risk of severe disease as initially reported from China." says lead author Leena B. Mithal, MD, MSCI, pediatric infectious diseases expert from Lurie Children's and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Most of the infants in our study had fever, which suggests that for young infants being evaluated because of fever, COVID-19 may be an important cause, particularly in a region with widespread community activity. However, evaluation for bacterial infection in young infants with fever remains important."

The study included 18 infants, none with a significant medical history. Of the 50 percent of these infants who were admitted to the hospital's general inpatient service, none required oxygen, respiratory support, or intensive care. Indications for admission were mainly clinical observation, monitoring of feeding tolerance, and ruling-out bacterial infection with empiric intravenous antibiotics in infants younger than 60 days. Of the infants admitted to the hospital, six out of nine had gastrointestinal (GI) symptoms (poor feeding, vomiting and diarrhea). Upper respiratory tract symptoms of cough and congestion preceded onset of GI symptoms. Young infants also had notably high viral loads in their nasal specimens despite mild clinical illness.

"It is unclear whether young infants with fever and a positive test for SARS-CoV-2 require hospital admission," says Dr. Mithal. "The decision to admit to the hospital is based on age, need for preemptive treatment of bacterial infection, clinical assessment, feeding tolerance, and adequacy of follow-up." There may be opportunities to utilize rapid SARS-CoV-2 testing to determine disposition of clinically well infants with fever."

Dr. Mithal and colleagues (Drs. Machut, Muller, and Kociolek) also observed an overrepresentation of Latinx ethnicity among their sample of infants with COVID-19 (78 percent). At the height of the COVID-19 pandemic in Chicago, over 40 percent of cases were in individuals of Latinx ethnicity.

"Although we expected that there would be many infants of Latinx ethnicity with COVID-19, there may be additional factors contributing to the disproportionate majority of Latinx cases we observed in this age group," says Dr. Mithal. "Access to sick-visit care in some primary care pediatric offices has been limited, with practices referring symptomatic children to the emergency department. Limited access to telemedicine care also may be a factor. Finally, there may be a greater likelihood of exposure with extended family living in the home or family members working outside the home during this pandemic."

What The Viewpoint Says: The challenges associated with conducting and assessing results of clinical trials during the COVID-19 pandemic are discussed in this Viewpoint.

Authors: Chaya S. Moskowitz, Ph.D., of the Memorial Sloan Kettering Cancer Center in New York, is the corresponding author.

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

(doi:10.1001/jamaoncol.2020.2370)

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

#  #  #

Media advisory: The full article is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamaoncology/fullarticle/10.1001/jamaoncol.2020.2370?guestAccessKey=4e1a1467-cfc9-4414-83f2-3f4ab9529322&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=061820