Body

For patients admitted to the intensive care unit in a hospital in Finland, increased workload for nurses and understaffing of nurses were linked with a higher likelihood that patients would experience multiple organ failure. The findings are published in the Journal of Advanced Nursing.

The levels of nursing workload and understaffing were at their worst on weekends.

The results emphasize the need to ensure that intensive care units are adequately staffed based on patient needs.

"The burden for critical care services has risen exponentially in response to the COVID-19 pandemic. The consequences of increased nursing workload during COVID-19 remains uncertain and need to be investigated in this light," said corresponding author Miia Jansson, PhD, MHSc, RN, of the University of Oulu, in Finland.

Low-dose aspirin significantly lowers cardiovascular disease risk but increases the risk of bleeding, according to a review published in the British Journal of Clinical Pharmacology.

Investigators conducted the review because the overall balance between risks and benefits of taking aspirin has been unclear. The team pooled information from analyses of all relevant observational studies and randomized controlled trials.

Use of low-dose aspirin in people without cardiovascular disease was associated with a 17% lower incidence of cardiovascular events (such as non-fatal heart attacks, non-fatal strokes, or cardiovascular-related deaths). Low-dose aspirin use was also associated with a 47% higher risk of gastrointestinal bleeding and a 34% higher risk of intracranial bleeding.

"These risks and benefits need to be weighted in formal decision analyses to guide aspirin use in primary prevention," said co-author Lee Smith, MSc, PhD, of Anglia Ruskin University, in the UK.?

The authors noted that although many dozens of health effects besides cardiovascular disease and bleeding have been assessed, evidence for these remains weak and therefore should not be a major consideration when deciding whether to use low-dose aspirin.

A new BJS (British Journal of Surgery) study indicates that breast cancer surgery is safe for patients who are older than 70 years of age, but age can influence the decision to undergo surgery.

The Bridging the Age Gap in Breast Cancer study was conducted to determine factors influencing treatment decisions and outcomes from surgery for older breast cancer patients. Of 3,375 recruited women, surgery was performed in 2,816 patients. Serious adverse events were rare and there were no deaths attributed to surgery. Age, ill health, and frailty all impacted decisions related to surgery. Surgery had a negative impact on quality of life and functional independence.

"These data are very reassuring for women facing treatment choices including surgery, but we must remember that 18% of this cohort did not have surgery, just primary endocrine therapy," said co-first author Jenna Morgan, MD, of the University of Sheffield Medical School, in the UK. "Surgeons select out the least fit women for primary endocrine therapy and undoubtedly if we operated on 'all comers' we would see more adverse outcomes. The issue is to know where to set the selection threshold for optimal outcomes." The investigators' online Age Gap Decision Tool may help support this decision-making process.

Most new viruses and other pathogens that arise in humans are transmitted from other animals, as in the case of the virus that causes COVID-19. A recent review published in Mammal Review examines how changes in land-use--such as deforestation, urbanization, and conversion to agriculture--have affected such transmission.

The review found that land-use changes cause changes in the behavior of animals, which affect the emergence of diseases in humans from a variety of animals, including rodents, livestock, and other mammals. However, many hosts, pathogens and impacts of land-use changes other than urbanization have been under-studied.

The review's authors call for more research to help predict how new diseases emerge and spread in response to land-use changes.

"We highlight major gaps in our understanding of how land-use change affects the spread of diseases from mammals to humans in terms of how key hosts, like bats, are affected, and how important land-use changes, such as agriculture, impact wild mammals and their interaction with livestock," said co-author Orly Razgour, PhD, of the University of Exeter, in the UK. "There is an urgent need for more studies that link animal ecology and responses to land-use change with pathogen ecology and disease spread."

Outdoor light at night was linked to a higher risk of breast cancer in a study published in the International Journal of Cancer.

For the study, investigators analyzed residential outdoor light at night estimated from satellite imagery in 1996 and assessed rates of breast cancer over 16 years of follow-up in 186,981 postmenopausal women.

Compared with the lowest level of exposure to outdoor light at night, the highest exposure was associated with a 10% higher risk of developing breast cancer during follow-up, after controlling for confounding factors.

"The small number of studies to investigate this question have often relied on subjective exposure data and yielded inconsistent results. We utilized an objective exposure measure--estimated outdoor light at night from satellite data," said senior author Rena Jones, PhD, MS, of the National Cancer Institute, part of the National Institutes of Health. "It will be important for future studies to accurately measure light at night exposure for individuals using a combination of objective measures, carefully designed questionnaires, and personal measurement devices."

The quest to discover how new diseases - such as Covid-19 - emerge and spread in response to global land-use change driven by human population expansion still contains "major gaps", researchers have claimed.

A team of experts from the University of Exeter has conducted a major study of how land-use changes, such as deforestation and urbanisation, influence the spread of diseases from mammals to humans.

Most new viruses and other pathogens that arise in humans are transmitted from other animals, as in the case of the virus that has caused Covid-19.

In the new review study, the researchers pinpointed one of the key factors that affect this transmission - the changes in land-use such as deforestation, urbanisation, and conversion to agriculture.

The effect of these land-use changes on the behaviour of animals, including rodents, livestock and other mammals, and risk of disease spread to humans has been mainly studied within the context of urbanisation.

The review, published in the journal Mammal Review, calls for more research to help predict how new diseases emerge and spread in response to land-use changes.

Orly Razgour, co-author and from the University of Exeter, said: "In this review, we highlight major gaps in our understanding of how land-use change affects the spread of diseases from mammals to humans, in terms of how key hosts, like bats, are affected, and how important land-use changes, such as agriculture, impact wild mammals and their interaction with livestock. There is an urgent need for more studies that link animal ecology and responses to land-use change with pathogen ecology and disease spread."

Around 75 per cent of emerging human pathogens, such as viruses, are transmitted from animals to humans. These include emerging infectious diseases (EIDs) - newly recognised or reappearing diseases detected in a population for the first time and which spread rapidly, such as covid-19.

While it is important to identify the source of the outbreak and the factors that allow these EID's to spread, the researchers claim that many methods for collecting such data are still under development.

Crucially, while areas such as South America and Asia have been studied more extensively, along with the effects of urbanisation, large swathes of the world including Africa are less well studied.

The researchers have called for more extensive studies to be conducted worldwide, to not only improve our understanding of how these diseases spread, but also to help policymakers identify the factors that alter the risk of emergence.

Rebekah White, co-author and also from the University of Exeter, added: "We need reliable surveillance and an understanding of how zoonotic diseases are able to spread to humans, but our results show that this information is not yet available for all hosts and pathogens. In fact, the epidemiology of many zoonotic pathogens is yet to be considered in relation to land use change at all, despite evidence suggesting that these changes can increase the risk of a disease emerging."

The effect of anthropogenic land use change on the spread of mammalian zoonotic diseases: a systematic review is published in Mammal Review on Wednesday, June 3rd 2020.

SAN ANTONIO (June 3, 2020) -- A team of researchers from The University of Texas Health Science Center at San Antonio confirmed the role of a certain protein in the development of high-grade kidney cancer. The researchers also showed that a higher level of the protein can be used as a marker to predict which tumors will develop treatment resistance and progress more rapidly.

Dharam Kaushik, MD, led the study published May 31 in the journal Translational Research.

Dr. Kaushik is an associate professor of urology in the Long School of Medicine at the university, also called UT Health San Antonio. He also is a genitourinary oncologic surgeon at the Mays Cancer Center, home to UT Health San Antonio MD Anderson.

"About 30% of patients with kidney cancer are not diagnosed until their cancer has spread to other parts of the body. Metastatic disease is notoriously resistant to current targeted therapies. In 2018, there were about 403,262 new cases of kidney cancer and 175,098 related deaths worldwide. Therefore, there is an urgent unmet need for developing new tools to predict which cancers will develop into high grade that are resistant to treatment," Dr. Kaushik said.

In previous preclinical and animal studies the researchers proved that the protein -- nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4 (Nox4) -- often called Nox4, was involved in promoting the more serious cancer.

In the current study, the researchers studied the treatment records of 350 patients who had kidney cancer between January 2013 and June 2016. Their results showed that Nox4 also concentrates in the nucleus of human kidney cancer cells. The findings were bolstered by a series of statistical analyses using clinical data of patients who survived or died from kidney cancer. The combined results suggest that nuclear Nox4 expression may be an independent marker of disease progression and poor survival in patients with high-grade, advanced-stage kidney cancer.

"Our analysis showed that a high level of nuclear Nox4 is an important marker predicting resistance to targeted therapy. To our knowledge, this is first report of nuclear Nox4 localization and the correlation with disease progression, poor survival and development of resistance to targeted/immune therapy in kidney cancer," he said.

During the study, the researchers also identified a smaller group of patients with high levels of nuclear Nox4 who had rapid disease progression or died within six months of surgery. "These patients would be ideal candidates for a future study of survival outcomes using adjuvant targeted therapy that includes a Nox4 inhibitor." Dr. Kaushik said.

As the COVID-19 pandemic continues to spread, researchers are turning their attention to the virus' biology, mechanism of action, and possible treatments. One of the targets are a group of immune cells called "neutrophils", which have been reported to infiltrate the respiratory tract of patients who have died from COVID-19.

The idea is that in their attempt to attack the virus, neutrophils might be making the disease's symptoms even worse by invading the lungs and exacerbating inflammation there. In order to find out if this is actually the case, scientists may use a mouse model whose neutrophils they deplete with "anti-neutrophil" antibodies.

The approach is used widely for studying neutrophils in a number of different conditions, including autoimmune diseases, chronic infection or inflammation, wound healing, and even some types of cancer. However, the neutrophil-depletion model is only partially effective, lacks specificity, and doesn't last long enough.

Now, scientists led by Etienne Meylan at EPFL, have identified the source of the problem and have developed an alternative model that addresses its shortcomings. The work is published in Nature Communications.

By attempting to deplete neutrophils in mice, the animals' bone marrow produces new neutrophils - which defeats the model's entire purpose. The researchers have now identified these neutrophils, and determined that the reason they survive is because they have a lower chance of being targeted by the antibodies.

To address this, the scientists have developed a double antibody depletion strategy that enhances neutrophil elimination. The method increases the killing rate of the antibodies, resulting in a profound, specific and long-lasting reduction in neutrophil numbers in blood and tissues.

"Our study could be useful to address the functional importance of neutrophils in acute or chronic infection, in inflammation or in cancer," says Meylan. "In particular, transgenic mouse models of SARS-CoV-2 infection coupled to our standardized neutrophil depletion strategies may help establish a causal link between this innate immune cell type and COVID-19."

Mexican cavefish spend their entire lives in the dark. With no need for vision, many of them lost functional eyes. In more than 30 varieties of Mexican cavefish, the eyes stop developing as embryos grow into larvae. Although they are still the same species as a sighted, surface-dwelling fish (Astyanax mexicanus), the cave-dwelling varieties carry genetic mutations that scientists have yet to fully unravel.

In a new study led by University of Maryland researchers, scientists have discovered that a mutation to the gene cystathionine beta-synthase "a" (cbsa) prevents blood flow to cavefish eyes during a critical phase of development. The lack of blood leads to withered, underdeveloped eyes covered by skin and connective tissue in all blind varieties of Mexican cavefish. The study was published in the journal Nature Communications on June 2, 2020.

"We know that genes controlling eye degeneration are scattered all over the Mexican cavefish genome," said William Jeffery, a professor of biology at UMD. "There may be 10 to 20 different genes involved, and this is the first time we've been able to pin down one specific gene and show the mechanism at work."

The cbsa gene is known to be responsible for a human disease called homocystinuria, which causes defective vision and can lead to hemorrhaging, stroke, heart attacks and premature death. Understanding how blind cavefish thrive with mutated cbsa may help researchers develop treatments for homocystinuria in the future.

Previous studies by Jeffery's team and others identified multiple regions in the cavefish genome that were likely to host genes responsible for eye degeneration during development. Each region contains up to a hundred genes. Investigating all of the regions at once is not practical. So, Jeffery's lab, along with collaborators from the National Institutes of Health and Stanford University, winnowed down the candidates by selecting the smallest of the promising regions and looking for genes that change expression during a critical period in cavefish development--the period when eye degeneration occurs.

Of the four candidate genes they identified, the cbsa gene was mutated in all blind cave-dwelling varieties of the species compared with the sighted, surface variety. What's more, the researchers saw parallels between blind cavefish and people with homocystinuria.

Patients with homocystinuria experience problems with vision as well as circulation, including blood clots, hemorrhages and aneurysms. For years, Jeffery and his team noticed that blind cavefish larvae have aneurysms and hemorrhages in the blood vessels of the eyes as the eyes begin to degenerate. The researchers suspected they found their target gene.

To verify that mutations to cbsa were involved in cavefish eye degeneration, the scientists used the gene editing tool CRISPR-Cas9 and another method to mutate the normal cbsa gene in the eggs from the sighted, surface variety of the fish. A large number of those eggs grew into adults with reduced or no eyes. Then, the researchers showed they could reverse eye degeneration in cavefish by injecting normal cbsa genetic material into cavefish embryos.

Jeffery and his colleagues believe damage to the vascular system around the eyes caused by mutated cbsa starves the developing eyes of oxygen and leads to their demise. But they say there is much more to learn about the process.

"This is only one of multiple genes responsible for eye degeneration," said Li Ma, a principal faculty specialist in biology and lead author of the study. "But now that we have successfully found the first, we know we can replicate this procedure to look for the others."

In addition, knowing how mutations to cbsa influence eye degeneration in otherwise healthy fish can lead to a better understanding of the gene's function in the vascular system.

"Mexican cavefish are not only surviving with homocystinuria, they're thriving," Jeffery said. "One thing we might be able to understand is how these fish recover from hemorrhages in the eye, which could provide insight into treatments for the disease in humans."

Most people in their 50s and older were capable home cooks just before COVID-19 struck America, but only 5% had ordered groceries online, according to a new national poll.

The cooking skills that enabled half of older adults to eat dinner at home six or seven days a week may have served them well during the height of the pandemic, the poll suggests. However, they may need added support for grocery shopping as the pandemic continues and older adults seek to avoid COVID-19.

Those who cooked dinner at home the most often before the pandemic were most likely to rate the overall health of their diet as excellent or very good. And those who said their physical health was excellent or very good were the most likely to say they were confident in their cooking skills or enjoyed cooking.

But the poll also shows vulnerability for many older adults. One in four said they already ate most or all of their meals alone, even before the pandemic led to social-distancing rules. Solo diners reported less healthy diets than those who rarely or never ate alone.

In addition, 11% of older adults ate fast food three times a week or more. This group was less likely to call their overall diet healthy.

A baseline of knowledge

The new results come from the National Poll on Healthy Aging, carried out by the University of Michigan Institute for Healthcare Policy and Innovation with support from AARP and Michigan Medicine, U-M's academic medical center. It involved a national sample of more than 2,000 adults aged 50 to 80.

The data provide a baseline understanding of the food shopping, cooking and dining out habits of older Americans just a few months before COVID-19 arrived. It was taken before the pandemic changed guidance about going to the grocery store, closed most sit-down restaurants and altered everything from incomes to social gatherings. AARP is doing new polling to explore the pandemic's effects on food-related habits.

"Public health guidance to avoid infection will continue to alter food-buying habits for many older people and those with health conditions, so further support for them may be needed to ensure healthy habits continue," says Julia Wolfson, Ph.D., M.P.P., an assistant professor of health management and policy at the U-M School of Public Health, who worked on the poll. "That could include more assistance with online ordering for no-contact pickup or delivery."

Dining out, eating together

The temporary closure of sit-down restaurants would have affected half of those polled, who said they dined out at least once in the week before they took the poll. Eleven percent had eaten in such restaurants three or more times in the last week.

"As restaurants begin to reopen for dining in or carry-out, the less-healthy options may beckon for those who have been cooking almost entirely at home," says Cindy Leung, Sc.D., M.P.H., an assistant professor of nutritional sciences at the U-M School of Public Health. "Restaurants could help support healthy eating by making sure affordable healthy options are available on menus and making sure nutrition information is transparent and easily available."

Meanwhile, pandemic-related income disruptions from lost jobs or retirement investment losses may mean fewer restaurant meals for many. This makes less-expensive home-cooking options, and food support such as federal "food stamp" SNAP benefits, Meals on Wheels and food pantries more important. The NPHA team recently reported on the cost-related food insecurity already experienced by many older adults before the pandemic.

It may also increase reliance on lower-cost, but less nutritious, fast food. Past research has shown that people who eat fast food often have lower quality of diet overall and higher rates of diet-linked health conditions such as obesity, diabetes, high blood pressure and some cancers.

Poll director Preeti Malani, M.D., who has training in both infectious diseases and geriatrics, notes that the new poll also intersects with the NPHA's past findings about loneliness and isolation among older adults.

"As people begin to have small gatherings, social isolation might ease for those who have been living and eating alone all spring," she says. "But as friends and family cautiously begin to gather with older adults, we should do so with a focus not just on preventing infection, but also on supporting healthier eating habits for everyone."

Looking to the future

Even as the intensity of the pandemic eases, at least for now, the continued attention to avoiding infection will be a focus for many older adults, who are most at risk of serious or fatal cases of COVID-19. That's why AARP is continuing to explore the shopping and dining habits of adults over 50, with new polling that is expected to be released this summer.

"This poll reveals that many adults 50 and older enjoyed eating out pre-pandemic. As restaurants reopen around the country, AARP recommends that Americans follow public health guidelines to stay protected, particularly at-risk older adults," says Alison Bryant, Ph.D., senior vice president of research for AARP. "We look forward to results from our ongoing research to see how older adults may have changed their eating habits and behaviors during this crisis."

The National Poll on Healthy Aging results are based on responses from a nationally representative sample of 2,048 adults aged 50 to 80 who answered a wide range of questions online. Questions were written, and data interpreted and compiled, by the IHPI team. Laptops and Internet access were provided to poll respondents who did not already have them.

CHICAGO --- For someone with a food or drug allergy, the risk of life-threatening anaphylactic shock lurks around every corner. A new Northwestern Medicine study shows there might be a pill that can be taken proactively to prevent mild to life-threatening anaphylaxis, no matter the cause.

Anaphylaxis is a severe, potentially life-threatening systemic allergic reaction that can occur within seconds or minutes of exposure to an allergen. It occurs in about one in 50 Americans, though many believe the rate is higher (closer to one in 20), according to the Asthma and Allergy Foundation of America. If a person's blood pressure drops so low during anaphylaxis or their airway closes up enough that they can't get enough oxygen to their organs, they enter anaphylactic shock.

How do the drugs stop an allergic reaction before it begins?

The drugs used in the study are known as BTK inhibitors. BTK stands for an enzyme called Bruton's tyrosine kinase, which is found inside cells, including mast cells. The reason BTK inhibitors work to block allergic reactions is that by inhibiting, or blocking, the BTK enzyme, the mast cells cannot be triggered by allergens and allergic antibody to release histamine and other allergic mediators.

The study used three different BTK inhibitors, which blocked allergic reactions when tested on human mast cells in a test tube. Additionally, the study used one U.S. Food and Drug Administration-approved oral drug, which successfully reduced or prevented allergic reactions, including severe, life-threatening anaphylactic reactions, in a new "humanized" mouse model of anaphylaxis. The mouse's organs contained transplanted human cells that, over several months, matured into human mast cells, the primary cells that react during allergic reactions.

This would be the first known treatment to prevent anaphylaxis other than avoiding the allergen. The findings could pave the way for future human clinical trials of such oral drugs to be used as a preventive treatment to avoid serious allergic reactions, said senior and corresponding author Dr. Bruce Bochner, the Samuel M. Feinberg Professor of Medicine at Northwestern University Feinberg School of Medicine.

"This pill could quite literally be life-changing and life-saving," Bochner said. "Imagine being able to take medication proactively to prevent a serious allergic reaction."

The study was published June 2 in the Journal of Clinical Investigation.

Many potential uses for the pill

"I've heard parents say, 'It would be nice to have my child take something while we're on vacation in case they accidentally eat the wrong food,' and we think these drugs could one day serve that purpose," Bochner said.

Additionally, Bochner said people who are at high risk of allergic exposures to life-saving antibiotics or people about to undergo oral food desensitization (gradually eating foods to build up a threshold to an allergic reaction) could take the pill as a preventive measure. If such drugs turn out to be safe and cheap enough for daily use, theoretically anyone with a serious allergy, including food allergies, could take it and be able to eat the foods they've been strictly avoiding, Bochner said.

For now, Bochner said the drug would likely be used preventatively, not for emergencies, like an EpiPen, which injects epinephrine into someone experiencing an allergic reaction to reverse the symptoms. But he and his team are considering exploring whether this sort of medication could be reformulated to be added to the EpiPen to be injected along with the epinephrine to see if it would better stop or abort anaphylaxis after it has begun.

Previous allergy research using these cancer drugs

In previous research, Dr. Jennifer Regan and Dr. Melanie Dispenza, both former allergy fellowship trainees working with Bochner, found that cancer patients taking the BTK inhibitor ibrutinib who were allergic to airborne allergens such as cat dander and ragweed pollen saw their allergic skin test reactivity reduced by 80 to 90% in one week. A subsequent study led by Dispenza showed the same thing happened to food allergy skin test reactions when healthy adults with food allergy took the drug for just a few days. Both pilot studies involved small numbers of subjects, but the findings were consistent.

"Inhibition of skin tests is a kind of a surrogate test for whether the drug is actually working," Bochner said. "So, one future goal is to give this medication to food- or drug-allergic subjects, show by skin testing that their allergic sensitivity has been blocked by the drug's effect and then give them the food or drug, expecting they will have little or no reaction."

BTK inhibitors are currently on the market for approximately $500 per day as a successful and less-toxic alternative to chemotherapy for patients with blood cancers like chronic lymphocytic leukemia and mantle cell lymphoma. They are not yet approved for use in children, who are more likely to have food allergies.

Women who use a class of tranquilisers called benzodiazepines before becoming pregnant are at greater risk of ectopic pregnancies, according to a study of nearly 1.7 million women.

The study, which is published today (Wednesday) in Human Reproduction [1], one of the world's leading reproductive medicine journals, found that the risk of an ectopic pregnancy, where the embryo starts developing outside the womb, usually in a fallopian tube, was 50% higher in women who had filled out a prescription for benzodiazepines in the 90 days before conception.

Ectopic pregnancies occur in one to two percent of pregnancies each year and are a serious health emergency for women. They are responsible for 6-13% of pregnancy-related deaths, and deaths from haemorrhaging is the leading cause of pregnancy-related death in the first trimester of pregnancy. They can also lead to serious complications and infertility.

Although pelvic infections, use of reproductive technology, intrauterine devices, smoking and increased age are known to be risk factors for ectopic pregnancies, approximately half of women who have an ectopic pregnancy do not have a known risk factor.

Dr Elizabeth Wall-Wieler, a postdoctoral research fellow at Stanford University School of Medicine (California, USA), who led the research, said: "Most studies that look at the use of medications such as benzodiazepines in pregnancy focus on the effect on the child. I am interested in the impact these drugs have on the health of the woman, and found that although the use of specific medications around conception could be affecting the reproductive system, there was no research on the use of psychotropic medication on the risk of ectopic pregnancy. This is despite the fact that benzodiazepine use in pregnancy has been found to be associated with miscarriage, adverse birth outcomes and child development outcomes."

Dr Wall-Wieler and her colleagues analysed data from US health insurance claims for 1,665,446 pregnancies in women aged between 15 and 44 between 1 November 2008 and 30 September 2015. Of these, one percent of women filled out at least two prescriptions for benzodiazepine totalling at least ten days supply in the 90 days before conception.

A total of 30,046 (2%) pregnancies were ectopic and 17,990 (1%) were to women who had a benzodiazepine prescription before conception.

"This translates to 80 excess ectopic pregnancies per 10,000 pregnancies among women exposed to benzodiazepine compared to those not exposed to benzodiazepine before conception," said Dr Wall-Wieler.

In order to check whether it might be the benzodiazepine use or the medical condition being treated that could be involved in the risk of ectopic pregnancy, the researchers carried out two separate analyses into women diagnosed with anxiety or insomnia.

"For each of these analyses, we saw that the association was not as strong as that seen in the group as a whole. This could mean that either the underlying condition could also be a risk factor for ectopic pregnancies, or that there are other factors that women with anxiety or insomnia share that are also potential risk factors for ectopic pregnancy," she said.

The researchers stress that their findings show only that benzodiazepine use is associated with an increased risk of ectopic pregnancy, not that it causes the condition.

"For women with specific health conditions such as anxiety or insomnia, benzodiazepines can be an important part of their treatment; yet a lot is unknown about how safe it is to use these drugs for women who become pregnant. This study shows that women who use benzodiazepines when they become pregnant are at higher risk of having an ectopic pregnancy. When identifying treatment options, women and their care providers should understand the benefits and risks associated with treatment options, and more options should be available that have been demonstrated to be safe to use before and during pregnancy," said Dr Wall-Wieler.

Co-author, Dr Thalia Robakis, an associate professor of psychiatry at the Icahn School of Medicine at Mount Sinai (New York, USA), said: "It is nearly always premature to draw firm conclusions from a single observational study and more research needs to be carried out. However, it is a relatively low risk intervention to recommend supervised, tapered cessation of benzodiazepine use prior to stopping one's contraception, as long as this can be safely and appropriately done under physician supervision. The potential for positive impact is high if even a small number of ectopic pregnancies can be avoided."

The researchers suggest that healthcare providers could consider carrying out early pelvic ultrasound for women who have used benzodiazepines before conception, particularly if they have other risk factors for the condition. However, many women do not know they have an ectopic pregnancy until they start experiencing pain or other complications.

Co-author, Dr Deirdre Lyell, professor of obstetrics and gynaecology at Stanford University School of Medicine, said: "For women using benzodiazepines, it is important that providers are aware of the potentially small increased risk of ectopic pregnancy, and women should be counselled about possible symptoms of ectopic pregnancy such as early blood spotting and lower abdominal pain. Early ultrasound and pregnancy hormone blood tests can help identify whether a pregnancy is ectopic or not."

Limitations of the study include the fact that the researchers relied on outpatient prescription data to identify benzodiazepine use before conception, which could result in over- or under-estimation of the actual consumption of the drug. They also relied on data from US health insurance claims to identify pregnancies and conception date, which could result in misclassification of pregnancy outcomes and the length of gestation.

Benzodiazepines include alprazolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, oxazepam, quazepam, temazepam and triazolam.

Favipiravir Observational Study Group (principal investigator: Dr. Yohei Doi, Fujita Health University) released a preliminary report of the Favipiravir Observational Study in Japan on the Japanese Association for Infectious Diseases website.

URL: http://www.kansensho.or.jp/uploads/files/topics/2019ncov/covid19_casereport_en_200529.pdf

Favipiraivr (brand name Avigan) is an anti-influenza drug which was developed by FUJIFILM Toyama Chemical Co., Ltd. Favipiravir can be administered to hospitalized patients with COVID-19 on a compassionate use basis on condition that the hospital participates in this observational study, obtains informed consent from the patient and the provider considers its use to be appropriate. There are two parts to this observational study: this observational study which is tasked with timely reporting of overall characteristics of patients who received anti-viral agents such as favipiravir, and a registry (COVID-19 Registry Japan), which is tasked with detailed reporting of COVID-19 patients in general.

This preliminary report contains entries made to the study database by COB May 15, 2020, consisting of 2,158 patients who received favpiravir for COVID-19 and describes their background, clinical course, outcome and adverse events. The study collects focused data using an online survey home and is not intended to generate a comprehensive data set. Data cleaning is performed as needed, such as when a duplicate entry is apparent, but otherwise the data are included as they were entered. Importantly, COVID-19 patients who did not receive anti-viral agents are not included in the study, thus comparison with untreated patients is not possible.

This study is conducted as part of research grant "Study on multicenter open-label randomized clinical trial of favipiravir to evaluate the viral load reduction effect in asymptomatic and mild patients with SARS-CoV2 infection/A multicenter observational study to evaluate the clinical course of moderate and severe patients receiving favipiravir" from the Japan Agency for Medical Research and Development to Fujita Health University.

Researchers have identified specific portions of the genetic codes of the COVID-19 and SARS viruses that may promote the viruses' lifecycles. The new technique is researchers' first tool for determining what genetic sequences stored as RNA - DNA's chemical cousin - are more stable.

"The current pandemic is very severe, and we want to contribute to the global acceleration of coronavirus research. Our research includes many types of viruses, but we decided to focus on our coronavirus results," said Professor Nobuyoshi Akimitsu, leader of the research team that performed the work and an expert in how cells withstand stress at the University of Tokyo Isotope Science Center.

Many families of viruses - including influenza viruses and coronaviruses - store their genetic sequence as RNA, which sneaks into human cells and tricks them into making more viruses. Viruses need their RNA to remain stable, resisting efforts from the host's immune system to degrade their RNA.

The research team named their technique Fate-seq because it aims to determine the fate of a genetic sequence, whether it will persist or degrade based on its stability.

"The Fate-seq technique is a very simple idea. We combined existing technologies in a new way," explained Akimitsu.

To perform Fate-seq, researchers first cut a genome into short fragments. Even extremely dangerous pathogens become harmless when researchers only work with short, separated, cut-up fragments of their genomes.

Researchers synthesized RNAs from the fragments of virus genomes and examined their fate, that is stability, by using next-generation sequencing, which allows researchers to quickly and simultaneously identify the exact sequence of individual strands of RNA. Computer programs can then identify patterns or interesting differences in the genetic sequences to study in further detail.

Researchers studied 11,848 RNA sequences from 26 virus genomes, including that of SARS-CoV, the virus that causes SARS, the sudden acute respiratory syndrome that killed 774 people in the first half of 2003. Researchers identified a total of 625 stable RNA fragments. Among the stable RNA fragments, 21 were from SARS-CoV.

Researchers compared the 21 SARS-CoV stable genome fragments to the full genetic sequence data available for other types of coronaviruses. Two of the stable fragments from the SARS-CoV are very common in other evolutionarily similar coronaviruses, including the virus that causes COVID-19, SARS-CoV-2.

Predictive models showed that those two stable RNA fragments likely form stem-and-loop structures. Stem-and-loops are short pieces of RNA that, instead of remaining a straight line, fold forward and bind onto themselves, forming a hairpin shape.

Most notably, one of the stable fragments only forms a stem-and-loop in the COVID-19 virus, not the SARS virus due to the few small but important differences in the viruses' RNA codes.

"The stem-and-loop structure of this SARS-CoV-2 genetic fragment is very stable in computer models and we propose that this structure might enhance survival of the virus," said Akimitsu.

In addition to better understanding dangerous viruses, researchers hope to use Fate-seq to understand the fundamental rules of RNA stability and advance new types of medicine. Human cells use RNA as the intermediate messenger between DNA and protein. Designing RNA-based drugs that are stable and easy for cells to translate into protein could treat genetic diseases without the hazards of altering our DNA.

Highlights

In a recent study, genes were predicted to be expressed at different levels in the tissues of individuals with PTSD compared with those without PTSD

Individuals with PTSD tended to have a lower expression of a gene called SNRNP35 in the brain, and they had a higher expression of a gene called ZNF140 in the blood

Examining how the expression of these genes affects PTSD susceptibility may point to new treatment and prevention strategies

Results from a new study suggest that whether certain genes are expressed -- turned on or off-- may play a role in susceptibility to post-traumatic stress disorder (PTSD). The study, which was conducted by an international team led by investigators at McLean Hospital and appears in the journal Cell Reports, may provide insights for PTSD prevention and treatment.

In the face of repeated, prolonged, or severe trauma, some individuals seem to be more susceptible to PTSD while others are resilient. Identifying which individuals may be susceptible to PTSD--and why--can help researchers develop effective interventions.

To investigate, scientists used genetic data from 195,684 individuals (29,539 with PTSD and 166,145 without), collected by the Psychiatric Genomics Consortium--PTSD Group (PGC-PTSD), to predict the expression patterns of genes in the brain and other tissues based on machine learning models. The team found two genes that were genetically predicted to be expressed at different levels in individuals with PTSD compared with those without PTSD.

Individuals with PTSD tended to have lower expression of a gene called SNRNP35 in the brain and higher expression of a gene called ZNF140 in the blood.

The researchers noted that SNRNP35 expression seems to be important in a region of the brain involved with managing stress. They also found that giving mice a high dose of a stress hormone decreases the expression of the SNRNP35 gene in the brain.

Regarding the ZNF140 gene, the protein coded by the gene is known to affect the expression of genes in immune cells circulating in the blood. Therefore, higher expression of ZNF140 may influence the body's immune response to increase susceptibility to PTSD.

"Our study provides a road map for follow-up studies to link PTSD risk with vulnerable populations and to develop and validate biological tests and 'druggable targets' for prevention and treatment," said lead author Nikolaos P. Daskalakis, MD, PhD, director of Neurogenomics and Translational Bioinformatics Laboratory at McLean Hospital.

The researchers noted that additional studies are also needed to uncover the detailed mechanisms behind different genes' effects on PTSD susceptibility and resilience.

"Identifying the genetic influences of PTSD could help us understand how the body responds to traumatic experiences and may point to new interventions to help affected patients," said senior author Kerry J. Ressler, MD, PhD, chief scientific officer and chief of McLean Hospital's Center of Excellence in Depression and Anxiety Disorders.