Body

Chronic liver disease affects men and women equally

Cirrhosis affects more than 4 million in U.S.

CHICAGO --- Prior studies have suggested women might have higher mortality of cirrhosis of the liver than men. Women are also less likely to receive liver transplantation.

But the research was unclear. A comprehensive new Northwestern Medicine study shows women are not more likely to die of liver cirrhosis than men, demonstrating that this chronic liver disease affects both men and women similarly.

"Despite how simple this question may seem, it is actually not easy to figure out," said Dr. Daniela Ladner, an associate professor of surgery at Northwestern University Feinberg School of Medicine, a Northwestern Medicine surgeon and the lead investigator for this study. "We knew that women are not receiving liver transplants at the same rate as men, but we did not know if liver cirrhosis leads to more death in women than in men."

The study showed women with cirrhosis have lower overall mortality but no difference in liver-related cause of death despite a lower rate of liver transplantation compared to men.

The paper was recently published in the Journal of Hepatology.

"The important takeaway should be that men and women should be treated similarly as their cirrhosis-related risk is the same," Ladner said. She noted population-based studies are important to truly understand the risks to different subgroups within the population.

Cirrhosis is a leading cause of death estimated to affect more than 4 million people in the United States.

The reasons for the past uncertainty is men and women have different causes of liver disease, different severities of liver disease and a different mix of other health conditions, Ladner said.

"The research is part of an ongoing push to make sure that patients are treated fairly and equitably in medicine," Ladner said. "In many areas it is increasingly shown that women are disadvantaged."

Although alcohol is a top cause of liver disease, most patients with cirrhosis do not have alcohol-related liver disease. The top causes of liver disease in the United States are due to a virus, Hepatitis C, and Non-alcoholic Steatohepatitis associated with obesity.

Investigators analyzed a cohort of 20,045 patients with cirrhosis using a Chicago-wide electronic health record database that was linked with the United Network for Organ Sharing and the state death registry cause of death data.

New tailored therapies offer exciting prospects for treating acute myeloid leukemia (AML), but taking advantage of them may require waiting a week or more for genetic testing before starting treatment, posing a dilemma for doctors and patients facing this deadly and often fast-moving disease. A new study bolsters the evidence that this approach is safe for most patients under careful clinical oversight.

Doctors can use information available in the first day or two after diagnosis to effectively determine which patients need standard chemotherapy urgently. The study, published today in the journal Blood, suggests in stable patients, doctors can wait for genetic tests in order to try a newer therapy that is targeted to their specific cancer.

"In the majority of patients, it seems safe to wait for the diagnostic results in order to assign the patient to the correct subgroup and select the appropriate treatment, rather than using the historic one-size-fits-all chemotherapy approach," said lead study author Christoph Ro?llig, MD, of Universita?tsklinikum Dresden in Germany. "We think a potential deterioration in prognosis, if it exists at all, will be much smaller than the clinical benefit a patient would gain by receiving the appropriate novel treatment."

AML is a cancer of the blood and bone marrow that often progresses very quickly. Most people receive their diagnosis within a few weeks after developing symptoms; if the leukemia is left untreated, most people die within a few months. As a result, for decades doctors have advised most of their patients to start chemotherapy immediately, often within a day of diagnosis.

Standard tests used to assess AML typically provide results within hours or days. These include blood tests that measure the number of white blood cells in the blood and biomarkers that indicate how quickly cancer cells are multiplying, as well as tests such as echocardiograms and lung assessments that doctors use to gauge whether a patient is healthy enough to undergo chemotherapy.

Genetic testing, on the other hand, may take one to two weeks, depending on the type of test used. The genetic characteristics of a patient's specific cancer can be used to predict which treatments will work best. For example, leukemias with certain genetic characteristics respond better to newer drugs than to the standard chemotherapy, while others do not respond to any available drugs and require a bone marrow transplant.

To determine whether delaying treatment has an impact on the course of the disease, the researchers analyzed data from 2,263 patients treated at hospitals throughout Germany. Comparing outcomes among patients who started treatment at different lengths of time after diagnosis, the researchers found that starting treatment later did not negatively affect patients' prognosis, as long as patients were clinically stable at the time of diagnosis.

On the whole, the length of time between diagnosis and treatment was not associated with any significant differences in patients' response to treatment, overall survival, or rate of early death. This held true for patients of all ages and for those with a variety of genetic and disease characteristics.

One caveat is that starting treatment earlier is necessary for patients whose AML is clinically unstable - for example, those with infections, extremely high white blood cell counts, rapidly multiplying cancer cells, or coagulation disorders caused by the leukemia, said Dr. Röllig. Doctors can assess these factors with initial diagnostic test results, usually available within a day or two.

Researchers said the findings not only underscore the value of tailored treatments, but also the importance of careful monitoring to determine when it is wise to start treatment before genetic test results are available.

"Clinical judgment is very, very important," said Dr. Ro?llig. "This study does not imply that we can become complacent. Every newly diagnosed patient must be closely monitored in order to avoid missing a worsening of the leukemia."

While the study included only patients treated in Germany, he said the results should be applicable in the Unites States and any developed country where intensive chemotherapy is available as the standard of care for AML.

Dr. Ro?llig also noted that, as a retrospective analysis, the study does not offer the same level of certainty as a randomized controlled trial. However, ethical considerations make a randomized trial infeasible for determining the optimal treatment timing for AML.

In the first few weeks of the lockdown of New Zealand in response to the COVID-19 pandemic, residents reported a slight increase in mental distress but higher levels of confidence in the government, science and the police, as well as greater patriotism, according to research published by the American Psychological Association.

"Our results suggest that, under the conditions of a strong and cohesive national response, people are more likely to lean on and trust their politicians, scientists, police and communities and ultimately more likely to comply with the lockdown and health guidelines," said Chris Sibley, PhD, a professor at the University of Auckland and lead author of the study published in the journal American Psychologist. "The absence of such a response, however, may provide fertile ground for division, lack of adherence to guidelines and conspiracy theories."

Sibley and his colleagues analyzed data from the New Zealand Attitudes and Values Study, a 20-year longitudinal survey of social attitudes, personality and health outcomes of more than 60,000 New Zealanders. The study was in the process of collecting its latest wave of data when the country went into lockdown, and more than 1,100 of the participants answered the questions in the 18 days afterward.

Researchers compared those responses to the same number of people of similar demographic and lifestyle variables, such as age, gender, ethnicity, mental health diagnosis and smoking behavior, who responded before the lockdown.

"We found that people in the pandemic lockdown group reported higher trust in science, politicians and police and higher levels of patriotism, compared to the pre-lockdown group," said Sibley. "We also found that in the days following the lockdown, people also reported slightly higher levels of psychological distress."

In the pre-lockdown group, 77.1% of participants reported no distress, 16.2% reported moderate distress and 6.6% reported serious distress. In the post-lockdown group 73.5% reported no distress, 21.1% reported moderate distress and 5.8% reported serious distress.

"Countries around the world are implementing measures to fight COVID-19, and their efforts will be enhanced by understanding the psychological effects of the pandemic, lockdowns and social distancing," said Sibley. "In the case of New Zealand, a strong national response appeared to correspond with an increase in trust, not only for our governmental institutions, but also science, which may have helped with compliance to guidelines that helped us beat the virus."

The country only had a little more than 100 confirmed cases in late March when the government decided to go to level 4 of its COVID-19 threat system, the highest level, where only essential work and grocery store and medical trips were allowed. New Zealand currently has fewer than 1,200 confirmed cases and 22 deaths, with no new confirmed cases since May 22. Cafes, movie theaters and restaurants have already been allowed to reopen.

"We hope that as the dust settles and governments and their communities review this global event, these results, along with others reported by other researchers in other countries, will inform a plan for what to do in the event of the next global crisis," said Sibley. "For example, we should anticipate that well-being will deteriorate and build mechanisms to provide support for those most affected."

Scientists can monitor biomolecular processes in live tissue by noninvasive optical methods, such as fluorescence imaging. However, the fluorescent dyes used for that purpose are often rather unstable, and photobleaching, lack of specificity, and poor pharmacokinetics are recurrent issues. US scientists have developed a molecular shield that stabilizes near-infrared fluorescent dyes and enhances their functionality. Their synthesis and characterization are reported in the journal Angewandte Chemie.

Fluorescence bioimaging often uses the near-infrared light region because this radiation can efficiently penetrate human tissue. Fluorescent dyes designed for this purpose usually have a flat, symmetrical molecular architecture, which favors absorption of near-infrared light, but the dyes also need to be water soluble and carry functional groups for conjugating with targeting biomolecules, for example, antibodies or tumor-binding peptides. A member of this class of fluorescent dyes, called heptamethine cyanines, or Cy7, is currently under investigation in surgical applications.

However, the Cy7 molecules have their drawbacks. Their light-absorbing chromophore is vulnerable to oxygen radicals, which leads to bleaching. In addition, the flat rigid molecules may aggregate and interact nonspecifically with other biomolecules, which slows down their clearance from the body.

To tackle these issues, Bradley D. Smith and his group at the University of Notre Dame, USA, improved the chemical structure of the dye. To protect the heptamethine chromophore from oxygen attack, they introduced a voluminous and smart shield. They attached a bulky aromatic group on top of the central part of the chromophore and furnished this top group with long shielding arms projecting over both faces of the chromophore, like a bird covering its nest with its wings.

The resulting dye, which the scientists call "sterically shielded heptamethine cyanine dye" or s775z, was water soluble and provided stable fluorescence. The shielded architecture prevented aggregation and photobleaching, the authors reported. The dye was exceptionally stable against chemical degradation and could be stored "indefinitely" in a common refrigerator, the authors wrote.

They also performed imaging studies in live mice and found that s775z, in contrast to all other studied dyes, did not accumulate in the blood clearance organs, but was washed out of the body quickly. Moreover, a cancer-targeted version of s775z accumulated at a high level in tumors and could be visualized by fluorescence imaging of the live mice.

The authors suggest that the new s775z dye will be useful for a wide range of biomedical imaging applications. They point out that the change from a flat molecule to a three-dimensional shielding architecture was the key to make this class of near-infrared fluorescence dyes more stable and efficient.

A tailored public health approach that accounts for variation in risks across populations, places and time could guide the next phase of Canada's coronavirus disease 2019 (COVID-19) response, argue authors in a commentary in CMAJ (Canadian Medical Association Journal).

Canada's early response to COVID-19 used a universal approach to containment, with isolation, testing and widespread closures of society, supported by mathematical models based on assumptions of homogeneity in risks.

"There is not one COVID-19 epidemic in Canada but, as with other pathogens, a multitude of microepidemics," writes Dr. Sharmistha Mishra, Unity Health and the University of Toronto, with coauthors. "Risks of acquisition, spread, clinical symptoms and disease severity are heterogeneous, as are access to and uptake of universal strategies of confinement, testing and isolation."

The COVID-19 pandemic, like others before it, has highlighted inequities and disparities that persist across Canada regarding number of cases, spread and severity within certain populations because of factors such as age, socioeconomic determinants and geography.

Applying a risk-tailored approach, which has been used in responding to other infectious diseases such as HIV, could help with local containment, anticipate surges at hospitals and the need for critical care beds, and optimize reopening of health and social services at local levels. It will require more granular data, investigative effort, and a focus on addressing social and health inequities rather than a one-size-fits-all approach to confinement and testing.

"Leveraging heterogeneity as a guiding principle in our COVID-19 response will not be easy and it will not be cheap, but it represents a path forward that affirms human rights and aligns with aspirations for equity in Canada's health systems," the authors conclude.

Results of the phase III Inter-B-NHL-ritux 2010 clinical trial reported today in the New England Journal of Medicine show 95 percent three-year survival for pediatric patients with advanced B-cell non-Hodgkin lymphoma treated with the addition of anti-cancer immunotherapy rituximab to standard chemotherapy. The trial represents a major international collaboration between the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) and the Children's Oncology Group (COG), and was led in the United States by Thomas Gross, MD, PhD, University of Colorado Cancer Center investigator and pediatric oncologist at Children's Hospital Colorado, and in Europe by Véronique Minard-Colin, MD and Catherine Patte, MD, both pediatric oncologists at the Gustave Roussy Department of Child and Adolescent Oncology in Paris, France. The addition of rituximab decreased treatment failures by 70 percent resulting in a 10 percent increase in the three-year survival rate seen with chemotherapy alone (LMB protocol).

"These outstanding results support rituximab as a new standard-of-care therapy for young patients with advanced B-cell non-Hodgkin lymphoma," Gross says.

Rituximab attaches to a protein called CD20 found on the surface of cancerous and healthy B-cells, helping the body's immune system to recognize and attack these cells. The drug previously earned FDA approval for use in combination with chemotherapy in adult patients with B-cell non-Hodgkin lymphoma. Though Burkitt lymphoma is the most common form of pediatric non-Hodgkin lymphoma, it is a rare disease requiring collaboration of institutions in 13 countries to identify and treat enough young patients to effectively test the benefit of adding rituximab. In all, the Inter-B-NHL ritux 2010 phase III randomized trial involved 328 patients, age 2-18 years, treated in 176 centers distributed over four continents (Europe, North America, Australia and Asia).

Gross says, "With more than 95 percent of kids alive and disease-free after three years, this looks like a cure for the vast majority of our patients, even those with the most advanced disease."

Burkitt lymphoma is one of the fastest growing cancers in humans, doubling in size every 1-2 days. It develops in the lymphatic system, meaning that it can form anywhere in the body, but is most often seen in areas with high concentrations of lymph nodes including the abdomen and neck.

"The Inter-B-NHL ritux 2010 trial is a fine example of international cooperation in academic clinical research, and shows the importance of public-private collaborations with the pharmaceutical industry," Gross says.

The study led to authorization of rituximab for children with B-cell non-Hodgkin lymphoma in Europe by the European Medicine Agency (EMA) and Dr. Gross is hopeful the FDA will use these results as the basis for approval in the United States of rituximab with this patient population.

Researchers in the Department of Biomedical Engineering at Texas A&M University are working on an entirely new way to detect blood clots, especially in pediatric patients.

Unlike what a biology textbook may show, blood vessels are not straight cylinders. They are tortuous, meaning they have complex curves, spirals and bends. When the blood reaches these curves, it makes changes to its fluid mechanics and interactions with the vessel wall. In a healthy person, these changes are in harmony with the tortuous microenvironment, but when diseased, these environments could lead to very complex flow conditions that activate proteins and cells that eventually lead to blood clots.

Dr. Abhishek Jain, assistant professor, said a big challenge in medicine is the medical devices used to detect clots and assess anti-blood clotting drug effects are entirely chemistry-based.

"They do not incorporate the flow through the naturally turning and twisting blood vessels, which are physical regulators of blood clotting," Jain said. "Therefore, the readouts from these current static systems are not highly predictive, and often result in false positives or false negatives."

To approach the problem from a new angle, researchers in Jain's lab at Texas A&M designed a microdevice that mimics tortuous blood vessels and created a diseased microenvironment in which blood may rapidly clot under flow. They showed this biomimetic blood clotting device could be used to design and monitor drugs that are given to patients who suffer from clotting disorders.

Jain said he can see several applications for the device, including critical care units and military trauma care units.

"It can be used in detection of clotting disorders and used in precision medicine where you would want to monitor pro-thrombotic or anti-thrombotic therapies and optimize the therapeutic approach," Jain said.

After developing the device, the team took it into the field for a pilot study. Working with Dr. Jun Teruya, chief of transfusion medicine at Texas Children's Hospital and Baylor College of Medicine, the team coordinated with clinicians to test the device with pediatric patients in critical care whose heart and lungs were not working properly.

These patients were in need of an extracorporeal membrane oxygenation (ECMO) machine, which provides cardiac and respiratory support in exchange of oxygen and carbon dioxide.

A common complication in ECMO is blood clotting, so patients are administered anticoagulants to prevent clotting. However, ECMO machines are also known to" eat" clotting proteins and platelets, which puts anticoagulated patients in further risk of bleeding. Anticoagulated pediatric patients on ECMO are especially prone to bleeding.

Current chemically based blood clotting tests are expensive, time-consuming, can be unreliable and require a skilled technician. Jain's team's tortuosity based microfluidic system doesn't require expensive chemicals, is quick, with results within 10-15 minutes, uses low blood sample volume and is easy to operate.

"The margin for error is essentially zero for these patients," Jain said. "Therefore, it's imperative that all the tests, not just clotting tests, must work and provide clinicians with quick and reliable information about their patient so they can provide the best care possible."

By having the opportunity to test their system with real patients, Jain said his team was able to demonstrate that their design could detect bleeding in anticoagulated patients with low platelet counts, which can help guide doctors to make better evidence-based clinical decisions for their patients.

The study was recently published in Nature's Scientific Reports journal.

For Jain and his team, the next stage is continued clinical studies to compare their approach to standard methods and hopefully demonstrate key performance advantages.

GRAND RAPIDS, Mich. (June 3, 2020) -- Van Andel Institute scientists have revealed the first known atomic structure of a "molecular machine" responsible for installing critical signaling proteins into cellular membranes.

The findings, published today in Nature, shed new light on how this process works, and lay the foundation for potential future therapies for diseases like cancer, Alzheimer's and cystic fibrosis.

"Determining precisely how proteins are assembled and function is central to understanding how the body works on the most basic level," said VAI Professor Huilin Li, Ph.D., leader of the Institute's Structural Biology Program and the study's senior author. "Our findings provide a map for future studies that one day could be translated into ways to combat disease."

Proteins are the molecular workhorses of the body, responsible for carrying out nearly every biological function. Roughly one-third of proteins are membrane proteins, whose jobs include relaying information to and from cells, and transporting ions and molecules through the cell membrane, among other vital tasks. These important roles make them popular marks for therapy -- more than half of the medications on the market target membrane proteins as a way to treat disease.

The endoplasmic reticulum membrane complex, or EMC, is embedded in the endoplasmic reticulum, a system of membranes within cells that plays a part in the creation, editing and transport of proteins. When the EMC's machinery breaks down, protein production can go awry, resulting in misshapen proteins that cannot do their jobs properly. For example, problems with the EMC are directly associated with cystic fibrosis, a genetic lung disease caused by improper assembly of a protein called CFTRDF508.

Using the Institute's powerful cryo-electron microscopes (cryo-EM), Li and his colleagues visualized the EMC of a common yeast strain. Yeast are commonly used models in biology because they have many of the same molecular systems as humans but are much simpler to study.

They found that the yeast EMC is larger than previously thought, containing eight protein subunits instead of six. Additionally, the core of the EMC resembles a protein that performs a similar function as the EMC in bacteria, suggesting that the EMC in eukaryotic organisms like mammals may have arisen from bacterial systems.

Collectively, the findings shed light on how membrane proteins become established in membranes and how they change from their unstructured form to their functional form once there -- processes that have not been well understood until now.

UNIVERSITY PARK, Pa. -- Antibiotics are important drugs that can save lives, but using them too often can lead to dangerous strains of antibiotic-resistant bacteria. New Penn State research explores how to communicate risk while encouraging people to seek information on their own.

The researchers found that a brief animated video was effective in convincing participants that antibiotic use can be risky, which in turn resulted in participants viewing antibiotics as less positive or useful, and also made them feel that they needed more information about antibiotics.

Yanmengqian Zhou, a graduate assistant in communication arts and sciences, said the study -- recently published in the Journal of Health Communication -- will help support future efforts to educate the public about the risks of antibiotics and antibiotic-resistant bacteria.

"Instead of seeing public apathy toward antibiotic stewardship as just a knowledge problem, we thought it might be more useful to see it as an information-seeking problem," Zhou said. "Our video promotes viewers' interest in gaining more information about the risks associated with antibiotics, and can help to develop public norm around information seeking."

According to the researchers, antibiotic resistance happens when certain bacteria survive exposure to antibiotics and then multiply, leading to antibiotic-resistant strains. This eventually leads to antibiotics becoming ineffective against certain bacteria, making infections much harder to treat.

Erina MacGeorge, professor of communication arts and sciences, said that additional recent research has suggested that the COVID-19 pandemic is increasing antibiotic use, which could promote antibiotic resistance even more. She said this could threaten the ability for antibiotics to treat the secondary bacterial infections that often kill COVID-19 patients, as well as their utility for everyone else.

"Antibiotic-resistant bacteria are already infecting at least 2.8 million Americans and killing 35,000 of them yearly, and those numbers are growing rapidly as bacteria evolve to develop greater resistance to antibiotic drugs," MacGeorge said. "The best solution we have currently is to use existing antibiotics as little as possible -- only when they are truly needed -- because the bacteria are less likely to evolve resistance when they are not under threat."

While there are many factors that contribute to antibiotics being overprescribed, MacGeorge said that if a patient expects or asks for antibiotics, a doctor may feel pressured to prescribe them. The researchers wanted to explore what influences people to seek information about the risks of using antibiotics and whether a video intervention could help increase the likelihood that they would look for information before seeking antibiotics.

In a previous study published in Science Communication and led by Dave Brinker, a senior researcher at Tufts University and Penn State alumnus, the researchers used a theory called the Risk Information Seeking and Processing (RISP) model to develop a video they hoped would encourage people to seek more information about the risks involved in using antibiotics.

"Seeking or avoiding information, and paying attention to it or not," Brinker said, "are both related to a person's attitudes about the seriousness of the risk, what they think the social expectations are for knowing about the risk, and how equipped they feel to actually understand and act upon risk information."

He added that generally, if people think they have enough information for their purposes, they won't seek out new information or pay much attention to information presented to them.

For the current study, the researchers at Penn State recruited 1000 participants to test the video message developed in the first study. The participants watched either the researchers' video, a video from the CDC, or no video.

Participants then completed questionnaires designed to measure several factors, such as how harmful participants thought antibiotics were, positive and negative feelings about antibiotics, how knowledgeable participants thought they were about the subject, and whether they were likely to seek more information about antibiotics, among others.

After analyzing the data, MacGeorge said the results showed that the video designed by the research team was effective at encouraging people to seek information about antibiotic resistance.

"Compared to study participants in the control group who watched no video, participants who saw our video perceived antibiotics as more risky and had less-positive feelings about them," MacGeorge said. "They also believed they knew more about them and were more capable of gathering information about them, and thought others would want them to know more, too."

MacGeorge said she and the other researchers were encouraged by the results since, even during restrictions due to the COVID-19 pandemic, videos are easily delivered to patients.

"A brief video intervention can be sent to patients on their phones or computers prior to primary care visits -- including telehealth visits -- or shown in the clinical context, like in a waiting or exam room," MacGeorge said. "Providers, practices, healthcare systems and public health practitioners could potentially use this video to easily help promote antibiotic stewardship."

Volume 11, Issue 22 of Oncotarget reported that the goal of this study was to explore the involvement of mi RNAs in beneficial effects exerted by physical activity in breast cancer prevention.

The levels of extracellular mi RNAs were evaluated in blood plasma before and after structured exercise by means of microarray analysis of 1,900 mi RNAs identifying mostly modulated mi RNAs. The different expressions of two mi RNAs involved in breast cancer progression, i. e. up-regulation of mi R-206 and down-regulation of anti-miR-30c, were the most striking effects induced by exercise.

The biological effects of these mi RNAs were investigated in MCF-7 human breast cancer cells.

The evaluation of these mi RNAs in the blood can be used as non-invasive biomarkers for breast cancer prevention.

Dr. Alessandra Pulliero from the Department of Health Sciences at The University of Genoa said, "The relevance of structured exercise for public health has been addressed by the World Health Organization, and its lack is estimated to be the main risk factor for 21-25% of breast and colon cancer cases, 27% of diabetes cases, and 30% of ischemic heart disease cases."

Breast cancer survivors engaging in structured exercise increase the drainage of lymph from their upper limbs, thereby decreasing the side effects of mastectomy, significantly lowering their risk of cancer relapse and improving their immune functions.

Structured exercise improves insulin resistance, reduces hyperinsulinaemia and reduces the risk for diabetes, which could explain the link between increased structured exercise and reduced risk for these cancers.

Recent findings indicate that women with a history of breast cancer who engage in more than 9 metabolic equivalent h/week of structured exercise after a breast cancer diagnosis had a significantly lower risk of death or breast cancer recurrence than women who were physically inactive.

Incubation of MCF-7 estrogen-responsive breast cancer cells and MDA-MB-231 triple-negative breast cancer cells treated with post-exercise serum, from both healthy volunteers and operated cancer patients resulted in a reduction of breast cancer cell viability in comparison with breast cancer cells incubated with pre-exercise sera.

Accordingly, the authors analyzed circulating mi RNAs expression profiles before and after structured exercise and evaluated their potential anti-cancer properties in breast cancer cells.

The Pulliero Research Team concluded in their Oncotarget Research Article, "this study provides evidence that miRNA modulation is a specific molecular mechanism through which structured exercise exerts preventive effects against cancer. The possibility of using these two miRNAs for breast cancer prevention is of interest. MicroRNA as delivered by lipid nanoparticles has been already been effective in mice in preventing NNK induced lung cancer [46]. However, insofar no similar experiments exist as far as concern breast cancer prevention.

Moreover, the evaluation of miR-206 and anti-miR-30c levels in the blood of breast cancer patients could be useful as non-invasive biomarkers in guiding future strategies for cancer prevention."

Women's risk of falling ill with cardiovascular disease, and dying from it, is lower than that of men of the same age, irrespective of where in the world they live. This is shown by a study of, in total, more than 160,000 men and women in 27 countries. Scientists at the University of Gothenburg, Sweden, are among those presenting the results.

Now published in The Lancet, the Prospective Urban Rural Epidemiological (PURE) study is the first worldwide to have documented differences between women and men in risk factors, treatment, proportions affected by heart attack (recurrent myocardial infarction, MI) and stroke, and the outcomes for those affected. The participants were monitored for more than 10 years.

One co-author of the study is Annika Rosengren, Professor of Medicine at Sahlgrenska Academy, University of Gothenburg. Sweden is the only country im Northern or Western Europe to be included Just over 4,000 of the participants come from Gothenburg and Skaraborg.

The results show that women had a more favorable risk pattern. Above all, fewer smoked; but the women also had lower blood pressure and healthier blood fat levels. Compared with men, women in good health with no history of cardiovascular disease, CVD, had a higher propensity to take preventive medication, have well-controlled blood pressure, and avoid smoking.

Concern is often expressed that women with CVD are given less intensive treatment than men. If this is true, it might have a negative influence. However, the researchers behind the present study think it is not a matter of discrimination.

"Our interpretation is that there doesn't seem to be discrimination against women. Rather, women have less marked changes in the coronary arteries, which means they don't need such intensive treatment," Rosengren says.

The study shows that men with, for example, myocardial infarction, MI, received invasive treatment, such as balloon dilation (coronary angioplasty) or coronary bypass surgery, more often than women. Despite this, women had less risk of a new MI.

The main difference in prognosis after MI is, instead, between poor and rich nations. In low-income countries like Bangladesh, India and Pakistan, roughly 40 percent of men and women alike die within 30 days after MI or stroke, while the corresponding proportion for high-income countries like Sweden and Canada is below 10 percent.

WASHINGTON--Per- and polyfluoroalkyl substance (PFAS) exposure may cause menopause to occur two years earlier in women, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Known as 'forever chemicals,' PFAS are manmade and used in a wide variety of nonstick and waterproof products and firefighting foams. PFAS chemicals can contaminate drinking water, and it has been estimated that 110 million Americans (one out of three) may consume drinking water contaminated with these chemicals.

"PFAS are everywhere. Once they enter the body, they don't break down and build up over time," said the study's lead author Ning Ding, Ph.D., M.P.H., of the University of Michigan School of Public Health in Ann Arbor, Mich. "Because of their persistence in humans and potentially detrimental effects on ovarian function, it is important to raise awareness of this issue and reduce exposure to these chemicals."

The researchers studied 1,120 midlife women from the Study of Women's Health Across the Nation, a 17-year-long prospective cohort study. They found that women with high PFAS levels in their blood samples reached menopause two years earlier than those with lower levels.

"Even menopause a few years earlier than usual could have a significant impact on cardiovascular and bone health, quality of life, and overall health in general among women," said corresponding author Sung Kyun Park, Sc.D., M.P.H., of the University of Michigan School of Public Health.

The number of heart attack patients seeking urgent hospital care has dropped by more than 50% during the COVID-19 outbreak, according to an extensive worldwide survey by the European Society of Cardiology (ESC). The findings are published in European Heart Journal - Quality of Care and Clinical Outcomes (EHJ-QCCO)1 and shown graphically online.

"This is the strongest evidence yet of the collateral damage caused by the pandemic. Fear of catching the coronavirus means even people in the midst of a life-threatening heart attack are too afraid to go to hospital for life-saving treatment. There has been a lack of public reassurance that every effort has been made to provide clean hospital areas for non-COVID-19 patients," said ESC President Professor Barbara Casadei.

"Yet the risk of dying of a heart attack is much greater than that of dying of COVID-19. Moreover, cardiac death is largely preventable if patients with a heart attack come to hospital in time to get treatment. What we are witnessing is an unnecessary loss of life. Our priority must be to stop this from happening. We must continue to save the lives we know how to save."

The ESC survey of 3,101 healthcare professionals in 141 countries was conducted in mid-April.

In the most severe heart attacks, known as ST-elevation myocardial infarctions (STEMIs), a major artery to the heart becomes blocked. Urgent treatment - either with a stent or clot busting drugs - restores blood flow, saves lives, and prevents disability. Delay causes irreversible damage to the heart muscle, substantially increasing the risk of heart failure and death.

The vast majority of hospital physicians and nurses answering the ESC survey reported a drop in the number of patients with these severe heart attacks coming to hospital, compared to before the COVID-19 crisis. On average, there was a 50% decrease. In addition, most respondents said that of those patients who did go to hospital, 48% arrived later than usual and beyond the optimal window for urgent treatment.

A separate survey of interventional cardiologists, doctors who insert stents to open blocked arteries, found a 28% increase in life-threatening complications among patients with heart attacks during the pandemic.2

This poll - conducted by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), a chapter of the ESC - surveyed more than 600 interventional cardiologists from 84 countries during the first two weeks of April. Nearly half of respondents said restoration of blood flow was delayed due to COVID-19 fears, a situation likely to lead to premature death and disability.

"The delays we are seeing in heart attack patients coming to hospital have significant harmful consequences," said EAPCI President-Elect, Professor Dariusz Dudek. "Patients who do not present promptly are in a far worse condition when they finally arrive at hospital and they are often too late to benefit from the life-saving treatment that we can provide."

"Don't delay if you have heart attack symptoms: call emergency," said Professor Dudek. "Every minute counts."

The EAPCI survey also revealed that the number of other procedures has been drastically reduced during the pandemic. "Interventions on heart valves and other procedures must resume as soon as the local COVID-19 situation allows it. We need to avoid needless suffering and death," said Professor Dudek.

Professor Casadei said: "Patients' fears of becoming infected by going to hospital must be addressed. They need to be assured that the in-hospital risk of coronavirus infection has been minimised for patients being admitted with heart attacks or strokes. If you have chest pain or other heart attack symptoms - such as pain in the throat, neck, back, stomach or shoulders that lasts for more than 15 minutes - you must call an ambulance. Remember that COVID-19 mortality is 10 times lower than that of an untreated heart attack. And rapid treatment for a heart attack works."

Different groups of drugs are used for the treatment of rheumatic conditions. They are intended to suppress the rogue immune system which attacks its own body. It is unclear to date whether the use of immunosuppressants increases the risk of a severe course in case of an infection with the novel coronavirus SARS-CoV-2. A current study published in the run-up to the European Congress of Rheumatology of the EULAR (European League Against Rheumatism) analysed, for the first time, 600 COVID-19 cases in rheumatic disease patients from 40 countries and investigated the impact of the choice of rheumatic disease therapy on potential hospitalisation and the course of COVID-19. The results of the study will be presented in an online press conference in the context of the EULAR Congress on 3 June 2020.

Data on the course of COVID-19 in patients with rheumatic conditions are still rare and limited to small numbers of cases. Patients with rheumatic diseases are concerned about the extent to which their condition increases the risk of a severe course and the impact of the intake of their immunosuppressants on this. "There is considerable uncertainty about the drug management in the context of rheumatic conditions," EULAR President Professor Dr Iain B. McInnes from Glasgow, Scotland, United Kingdom explains.

Scientists have now addressed the question to what extent the different groups of drugs1 increase the probability of hospitalisation in rheumatic disease patients with COVID-19. For this purpose, they analysed a series of cases involving persons with rheumatic conditions and COVID-19 from the combined EULAR and Global Rheumatology Alliance COVID-19 registries, dating from between 24 March 2020 and 20 April 2020. The study included a total of 600 cases from 40 countries.

The researchers analysed the patients' age, sex, whether they smoked or not, the rheumatic disease diagnosis, comorbidities and medication against rheumatic conditions taken immediately prior to the infection. The result: The intake of conventional disease-modifying antirheumatic drugs (csDMARDs) - such as anti-malarial drugs or methotrexate - alone or in combination with biologics (e.g. TNF-alpha inhibitors), or the intake of nonsteroidal anti-inflammatory drugs (NSAIDs) was not associated with hospitalisation. The intake of TNF-alpha inhibitors was associated with a reduced probability of hospitalisation, while no association with the intake of anti-malarial drugs was observed.

Treatment with more than 10 mg prednisone per day - corresponding to a moderate to high dose - was associated with a higher probability of hospitalisation. Prednisone is a glucocorticoid frequently used in rheumatology as a fast-acting anti-inflammatory drug.

Less than half of the patients required hospitalisation (277; 46 percent), while 55 fatalities (9 percent) occurred. This should not be interpreted as the true rate of hospitalisation and death among patients with rheumatic disease infected with SARS-CoV-2. Due to the mechanism by which case information is collected severe cases are more likely to be reported to the database (i.e. mild or asymptomatic cases are less likely to be reported) therefore artificially increasing the rate of hospitalisation/death in the group of reported patients.

"The study shows that most patients with rheumatological conditions recover from COVID-19 - independent of the medication they receive," says Professor Dr John Isaacs from The University of Newcastle, United Kingdom, Scientific Chair of the EULAR Scientific Committee. "It is necessary, however, to gather more knowledge about the course of an infection with the novel coronavirus in patients with inflammatory rheumatic conditions."

Within the space of only a few weeks, rheumatologists from all over the world teamed up in order to establish an international COVID-19 registry, an effort supported by EULAR that created a mirroring COVID-19 registry. "There is an urgent need to understand the outcome of patients who have been infected with SARS-CoV-2 while at the same time receiving steroids, synthetic or biological disease-modifying anti-rheumatic drugs and nonsteroidal anti-inflammatory drugs," Dr Pedro Machado, Chair of the EULAR Standing Committee on Epidemiology and Health Services Research and co-senior author of the study, points out. "This will support rheumatologists and other health care professionals, such as specialist nurses, in advising their patients and improving their care."

A recent study found that nitrogen-containing bisphosphonates (N-BPs) such as alendronate, which are widely used to treat postmenopausal osteoporosis, are linked with lower risks of pneumonia and of dying from pneumonia. The results are published in the Journal of Bone and Mineral Research.

The study included 4,041 patients with hip fractures who received N-BPs and 11,802 who did not. Over a median follow-up time of 2.7 years, N-BPs were associated with a 24% lower risk of pneumonia compared with no treatment (69 versus 90 cases per 1,000 people per year).

A similar association was observed with pneumonia mortality, with a 35% lower risk associated with N-BPs (23 versus 35 per 1,000 patients per year for the N-BP and non-N-BP groups, respectively).

Results from previous animal studies indicate that N-BP treatment leads to a high concentration of N-BPs in the respiratory tract. "Together with its anti-inflammatory and immune-modulatory properties, this may explain why N-BPs were associated with reduced risk of pneumonia, as revealed in our study," said senior author Ching-Lung Cheung, PhD, of The University of Hong Kong. He added that studying the potential of N-BPs for treating symptoms of COVID-19 may be warranted.