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In research published today in The Lancet and funded by National Institute for Health Research (NIHR), researchers from King's College London have found that early, planned delivery for women with pre-term pre-eclampsia reduces complications and severe hypertension, as well as costs, compared to the current method of care.

The team from the Department of Women & Children's Health at King's carried out a trial comparing the current and new methods in women suffering from pre-eclampsia at 34-37 weeks of pregnancy, to see if they could reduce adverse outcomes for the mother such as hypertension, and without impacting substantially on the baby.

They found that planned delivery - starting delivery (either by induction of labour or by Caesarean section if it is needed) within 48 hours of the diagnosis of pre-term pre-eclampsia being made - reduced maternal complications including hypertension. They also found that the women in that group had more vaginal deliveries compared to those who experience the current method of care - specialist assessment of mother and unborn baby until 37 weeks, with delivery sooner if the clinical scenario changes and there is concern over severe pre-eclampsia and associated complications. Though planned delivery did lead to more neonatal unit admissions for prematurity, there were no other complications for the baby (such as more breathing problems) compared to the current method. Planned delivery also comes with lower costs compared to the current method of care in the UK.

Pre-eclampsia is a condition that affects around 1 in 20 pregnant women, usually during the second half of pregnancy affecting approximately 40,000 women annually in the UK. If untreated, it can progress to cause complications in the woman, including damage to vital organs, fits and can be fatal for the woman and baby. Globally, 100 women die as a result of the condition every day.

Current guidelines recommend prompt delivery after 37 weeks of pregnancy. However, for women with late preterm pre-eclampsia (defined as 34-37 weeks pregnant) the recommendations are less clear.

Lead author Professor Lucy Chappell from King's College London said: "We wanted to find out what the best timing of delivery was for a woman with preterm pre-eclampsia. Clinical practice has already changed for women with term pre-eclampsia as a result of a previous trial showing that planned delivery was better. We felt that it was important to ask a similar question at 34-37 weeks of pregnancy to see whether it would help the woman and her baby to continue the pregnancy or get on with delivery.

"Our trial supports offering initiation of delivery in women with late preterm pre-eclampsia. Doctors and women will need to consider the trade-off between lower maternal complications and severe hypertension against more neonatal unit admissions, but the trial results tell us that these babies were not sicker from being born earlier. We suggest that these results should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery."

Marcus Green, CEO for Action on Pre-eclampsia, said: 'We welcome this research and results. Anything that empowers women and gives them more knowledge from which they can make choices about safer birth is great news.'

An individual's trust in institutions such as the CDC, and how close they live to a recent measles outbreak, may affect their attitudes on measles vaccination, according to a study published August 28, 2019 in the open-access journal PLOS ONE by Florian Justwan of the University of Idaho, USA, and colleagues.

In both the US and globally, there is growing vaccine hesitancy, which can manifest itself in increased non-medical exemption rates, decreased vaccination rates and increased outbreaks of vaccine-preventable diseases. The formation of attitudes about vaccination is complex and linked to many factors including media and peer group influence, distrust of science, information access, and socio-economic barriers.

In the new study, researchers surveyed 1,006 online respondents across the United States about their political beliefs, vaccination attitudes and demographics. The survey was carried out in January 2017, following local outbreaks of measles in 2016. The respondent pool was generated by a market research firm to be a nationally representative sample of the U.S. voting age population and the final sample matched known population in terms of gender, age, income race and Census region.

The researchers found that an individual's proximity to a measles outbreak independent had no independent effect on measles vaccination attitudes (p = 0.43). However, they found that trust in government medical experts is strongly and positively related to vaccination attitudes (p=0.01). Moreover, the study uncovered an interactive relationship between the two variables. People who are skeptical of the CDC and similar institutions and live farther away from a disease outbreak harbor less favorable vaccination views than those who are skeptical but live in close proximity to an outbreak. People who have high levels of trust are not affected by disease proximity.

The research therefore suggests that, unlike people who trust government experts, people who are skeptical of the CDC and similar institutions may consider whether or not a given disease occurs nearby when making decisions about vaccination.

Justwan adds: "In this paper, we explore whether people's vaccination attitudes with regards to measles are shaped by how far away they live from a recent outbreak. We find that this is the case - but only for individuals who also distrust government medical experts. Put differently: citizens who are skeptical of the CDC and similar institutions base their vaccination decision-making to some degree on whether or not a given disease occurs in close vicinity to their community."

Washington, DC - August 28, 2019 - The pathogen Clostridium difficile, which causes one of the most common hospital-acquired infections in the United States, may have accomplices that until now have gone largely unnoticed.

This week in mSphere, researchers report finding fungi that flourish in people infected with the C. difficile pathogen. The findings suggest that transkingdom interactions between fungal and bacterial species play an important role in nosocomial infections, and the researchers hope that exploiting those interactions may point to a new way to treat C. difficile.

"The development of C. difficile infection is apparently influenced both by bacterial pathogens and fungi particular to this disease." said colorectal surgeon and senior author David Stewart, MD, at the University of Arizona College of Medicine, in Tucson. "Until now, fungi have been understudied and under-appreciated in the gut microbiome."

Fungal taxa make up a tiny fraction of intestinal microbes -- between one-thousandth and one-tenth of one percent in healthy people. However, the new study suggests that even with low representation they may play an outsized role in dangerous infections.

"This discovery was just astounding to use, knowing that they're such a small percentage of organisms in the gut," said microbiologist and lead author Regina Lamendella, Ph.D., at Juniata College in Huntingdon, Pa.

The researchers - largely made up of a team of undergraduates from Juniata -- used high-throughput sequencing to identify fungal and bacterial populations in stool samples collected from 49 hospital patients. Eighteen of those had tested positive for C. difficile. The data revealed distinct species -- two fungal and nine bacterial -- that were enriched in the group of patients with C. difficile infections. Further analyses identified additional fungi with elevated abundances in samples from infected patients. In addition, the researchers found that increases in some fungal populations were tied to decreases in the population of some helpful bacteria. They didn't find the same negative relationship between fungi and bacteria in patients without infections.

The researchers also conducted bacterial gene expression analyses, which led them to identify new pathways -- or interactions between genes -- associated with C. difficile infections. Those pathways pointed to still other bacterial species, including Escherichia coli, that may contribute to the dysbosis, or imbalance among bacterial species in the gut, associated with C. difficile.

The study suggests that patients with C. difficile infections host a mix of bacteria and fungi that's specific to the disease, and could help it resist treatment, Lamendella said. However, she cautions that it's too soon to know which fungal species are the most important, or to know what role the fungi are playing.

"Where we're headed next is to try to pin down the interaction between C. diff and specific fungi, as well as other organisms within the gut," she said. "Is that relationship antagonistic and negative, or positive? Do the fungi actually perpetuate gut dysbiosis?"

The researchers believe it's a research question worth pursuing. C. difficile infection is difficult to control, largely because it affects patients who have already been treated with antibiotics. If researchers pin down a clear cause-and-effect relationship between fungal species and C. difficile infection, they might be able to develop treatments that don't involve antibiotics.

"The fungi could be a therapeutic target," Stewart said. "It would raise that possibility that we could repurpose already-approved antifungal drugs to treat C. diff or other diseases."

Plant diseases, especially those caused by fungal pathogens, jeopardize global crop biosecurity and preventing them requires rapid detection and identification of causal agents. Traditional methods for crop disease diagnosis rely on the expertise of pathologists who can identify diseases by eye, but this approach comes with many limitations, including the reliance on physical appearance of disease symptoms.

Also of note, this traditional method does not allow for the rapid identification of unknown pathogens during an outbreak. This limitation was made obvious recently in Bangladesh, when wheat crops were devastated by an invasion of South American races of wheat blast fungus.

As wheat is one of the world's most important crops, a group of Australia-based scientists wanted to address this limitation by developing a new method for analyzing pathogen DNA in wheat leaf samples. Using a portable DNA sequencer, they were able to achieve early-stage and broad-range detection of pathogens in wheat--and they were also able to characterize all organisms in the wheat and confirmed the presence of an unexpected diseases not previously diagnosed by pathologists.

According to the scientists behind this research, "A combination of on-site and centralized sequencing approaches would, in future, revolutionize management of agricultural biosecurity and reduce crop loss." Additionally, these methods can be incorporated into routine field diseases monitoring and biosecurity monitoring at national borders to save time and money and prevent another devastating outbreak like the one seen in Bangladesh.

This research, discussed in the open access article "Pathogen Detection and Microbiome Analysis of Infected Wheat Using a Portable DNA Sequencer," also explores the way this new strategy can identify diseases-inhibiting microbes for use in environmentally friendly control of diseases. This research was made available online in May 2019 ahead of final publication in the June issue of the fully open access Phytobiomes Journal.

The force of blood traveling through your arteries and veins determines much of your heart health. High blood pressure can lead to heart disease, heart failure, heart attack, stroke and chronic kidney disease, and when it's coupled with type 1 diabetes and pregnancy, it can put both the mother and the baby at risk.

In a recent paper in The Journal of Clinical Endocrinology & Metabolism, researchers at the Medical University of South Carolina look at preeclampsia, a combination of high blood pressure and pregnancy, when it coincides with type 1 diabetes.

The general female population has a 5% chance of developing preeclampsia during pregnancy, but that chance increases to 20% for diabetic women. "By studying these patients, we have identified different markers that could help predict the complication before its onset," said Clare Kelly, an endocrine researcher who worked with MUSC endocrinologist Timothy Lyons on the paper.

According to the Centers for Disease Control and Prevention, preeclampsia can lead to a baby being born early and can put the mother at risk of a seizure or stroke during delivery. It can also lead to damage in the kidneys, liver, lungs, heart or eyes and can increase a patient's risk for cardiovascular disease in the future.

Some current treatments for preeclampsia include taking aspirin or remaining on bedrest, and the only cure is delivering the baby. But by monitoring someone at high risk for preeclampsia, physicians can work closely with these patients and take proactive measures to keep their blood pressure down.

Each patient in the study could be categorized as having one of three phenotypes: 1-1, 1-2 and 2-2. Phenotypes describe the way a person expresses their genetic makeup and can be determined using a simple, one-time blood test. By looking at the three groups and their lipoproteins, the compounds that transport fat throughout their bodies, the researchers were able to determine that the diabetic patients with a 2-2 phenotype who also had elevated lipoproteins were at greater risk for preeclampsia.

Previous studies have examined lipoprotein levels and diabetes, but this one concluded that these markers were indicative of risk only for patients with the specific phenotype. Otherwise, looking at the biomarkers was not useful. "Currently, we're taking the more reactive approach when it comes to preeclampsia," said Kelly. "But if we know a patient is diabetic and has the 2-2 phenotype, we can monitor her more closely throughout her pregnancy and treat it proactively."

While high lipoprotein levels in conjunction with the 2-2 phenotype were associated with an increased risk of preeclampsia, this scenario is not yet proven to be causative. Currently, there are various hypotheses about what contributes to preeclampsia, like insufficient blood flow to the uterus or poor nutrition, but the root cause of the disease is not known. By looking at the genetics and conditions associated with preeclampsia, researchers are moving one step closer to understanding what causes it and potentially how to prevent it.

"While we were looking at pregnant women with type 1 diabetes specifically," said Kelly, "we're hoping to extend some of our findings to women with type 2 diabetes and gestational diabetes as well as the general population of diabetics when identifying people at risk for hypertension."

A new platform that combines two established imaging methods can peer into both the structure and molecular makeup of the prostate in men with prostate cancer. The technology is more sensitive and comprehensive compared to current "gold standard" methods, indicating it could allow clinicians to diagnose and monitor prostate cancers in real time with greater accuracy and confidence. Prostate cancer affects over 1.2 million people worldwide and is one of the most common malignancies in men. Most cases are diagnosed using biopsy and a method called transrectal ultrasound (TRUS), which uses sound waves to image the prostate and its surrounding tissues. However, TRUS cannot probe the prostate's molecular profile, meaning it misses key molecular markers and often gives false negatives and positives. To overcome these limitations, Sri-Rajasekhar Kothapalli and colleagues created TRUSPA, a device that integrates TRUS with a hybrid optical-ultrasound method named photoacoustic imaging. Combining these approaches allows TRUSPA to detect anatomical features of the prostate such as blood vessels in real time, as well as detailed molecular information within tumors. The platform worked as intended in mouse models of prostate cancer and in isolated human prostates and administering an FDA-approved dye enhanced image contrast. In an experiment with 20 male subjects, TRUSPA provided clear images of the prostate's anatomy - peering as deep as six centimeters into tissue - and could distinguish a malignant region of the prostate in one patient with advanced disease. Kothapalli et al. will investigate how TRUSPA could be developed to detect specific biomarkers of prostate cancer, which could further boost its accuracy and clinical potential.

A review of the autopsy reports of 252 men and women who died of acquired immunodeficiency syndrome (AIDS) in New York City between 1984 and 2016 reveals several long-term trends in combatting the epidemic. The infectious disease is known for drastically lowering the body's immune defenses and is spread by the human immunodeficiency virus, or HIV.

The researchers at NYU School of Medicine and NYU Long Island School of Medicine who led the study say their analysis is the largest review of autopsy-verified causes of death since a similar California report in 2000, and almost 40 years since the epidemic was recognized by health officials in 1981.

"Our study accurately reflects the history of the epidemic in New York City, which still has the highest number of new HIV infections per year in the United States," says senior study investigator Amy Rapkiewicz, MD.

"Autopsy reports reliably tell the whole disease story and why people are still dying from it," says Rapkiewicz, an associate professor in the Department of Pathology at NYU Langone Health and vice chair of pathology at NYU Winthrop Hospital on Long Island. "That is because there is often a difference between the immediately reported cause of death, such as a heart attack, and the actual cause of death, whether from obesity, drug use, or HIV/AIDS."

Among the key findings in the report, publishing in the Archives of Pathology and Laboratory Medicine online Aug. 28, is that early in the HIV epidemic in 1984, the average age of death in the city from AIDS was 36. By 2010, the average age had risen to 54.

Rapkiewicz credits this increase in lifespan to the development of combination antiviral drug therapies in the 1990s that prevent HIV from reproducing and infecting other cells, but, she says, "people are still dying predominantly from the underlying disease and not just factors related to old age."

According to researchers, infections such as pneumocystis pneumonia in the lungs are still the leading cause of death (accounting for 100 percent of deaths between 1984 and 1987, 52 percent between 1996 and 1999, and 86 percent from 2012 to 2016). "Even a treated HIV-positive patient is immunocompromised and at increased risk of dying from pneumonia," says Rapkiewicz.

And now that people are living longer with HIV, she says, other common co-infections, such as viral hepatitis C, which takes years to damage the liver, are starting to emerge as causes and contributors of death. Three-quarters of those autopsied between 2014 and 2016 had hepatitis C and cirrhosis, a severe and potentially deadly scarring of the liver.

However, researchers expect that recent advances in drug therapies for hepatitis C will drive down these numbers in the near future.

One study finding that remains to be explained by future autopsy reports, they say, is the sharp increase in hardened and fat-narrowed arteries from atherosclerosis among those dying with HIV. Between 1988 and 1991, atherosclerosis was found in 21 percent of those autopsied, but for the years 2008 to 2011, the condition was found in 54 percent.

Lead study investigator Sobia Nizami, MD, a clinical fellow in infectious diseases at NYU Langone, says it is difficult to assess if this trend is due to HIV-positive people simply living longer, overeating, and adopting the sedentary lifestyles widely seen among non-infected Americans, or if something more worrisome, such as long-term side effects of antiviral medications, are at the root of the problem. Body fat deposits seen with earlier anti-HIV drugs were, she says, mostly eliminated with later versions of the drugs.

The investigators say their study was designed in part to educate more clinicians, not just physicians, but also physician assistants and nurse practitioners, about the importance of accurately documenting death certificates to properly reflect people's HIV status and the main cause of death. The researchers caution that their analysis only reflects the disease's trends in New York City, not nationally.

A KAIST research team reported the development of a DNA vaccine for Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) which completely protects against lethal infection in ferrets. The team confirmed that ferrets immunized with DNA vaccines encoding all SFTSV proteins showed 100% survival rate without detectable viremia and did not develop any clinical symptoms. This study was published in Nature Communications on August 23.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is a newly emerging tick-borne infectious disease. The disease causes fever, severe thrombocytopenia, leukocytopenia as well as vomiting and diarrhea. Severe cases end up with organ system failure often accompanied by hemorrhages, and its mortality rate stands at 10-20%.

The viral disease has been endemic to East Asia but the spread of the tick vector to North America increases the likelihood of potential outbreak beyond the Far East Asia. The World Health Organization (WHO) has also put SFTSV into the priority pathogen requiring urgent attention category. Currently, no vaccine has been available to prevent SFTS.

The research team led by Professor Su-Hyung Park noted that DNA vaccines induce broader immunity to multiple antigens than traditional ones. Moreover, DNA vaccines stimulate both T cell and antibody immunity, which make them suitable for vaccine development.

They constructed DNA vaccines that encode full-length Gn, Gc, N, NS, and RNA polymerase genes based on common sequences of 31 SFTSV strains isolated from patients. Their vaccine candidates induced both neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets.

To investigate the vaccine's efficacy in vivo, the research team applied a recently developed ferret model that recapitulates fatal clinical symptoms in SFTSV infection in humans. Vaccinated ferrets were completely protected from lethal SFTSV challenge without SFTSV detection in their blood, whereas all control ferrets died within 10 days' post-infection.

The KAIST team found that anti-envelope antibodies play an important role in protective immunity, suggesting that envelope glycoproteins of SFTSV may be the most effective antigens for inducing protective immunity. Moreover, the study revealed that T cell responses specific to non-envelope proteins of SFTSV also can contribute to protection against SFTSV infection.

Professor Park said, "This is the first study demonstrating complete protection against lethal SFTSV challenge using an immunocompetent, middle-sized animal model with clinical manifestations of SFTSV infection. We believe this study provides valuable insights into designing preventive vaccines for SFTSV."

Pregnancy can be a time of anxious uncertainty, particularly if there are any risks of complications. The question always arises, from parents, grandparents, friends and others: "Will the baby be OK?"

In cases where the baby has been exposed to opioids in the womb, the answer is unclear. As part of a National Institutes of Health initiative to study the effects of a child's environment on his or her life outcomes, University of Utah developmental psychologist Elisabeth Conradt and her colleagues collected and reviewed 52 publications to identify what's known so far about how prenatal opioid exposure affects childhood outcomes and development. The review is published in Pediatrics.

"Right now, the number one question mothers, fathers and clinicians have when they see that a mother is using opioids while pregnant is how will this opioid exposure affect the child's health?" Conradt says. "We cannot answer that question right now with the existing data that we have."

Effects at birth

For this review study, the researchers focused particularly on 11 studies of children diagnosed with neonatal opioid withdrawal syndrome, or NOWS. It's a condition diagnosed three to four days after birth and includes symptoms such as feeding problems, tremors and a high-pitched cry. Little is known about how a diagnosis of NOWS is connected to a child's neurological development throughout life.

The current question about babies exposed to opioids, Conradt says, echoes questions from the 1980s and '90s about babies exposed to crack cocaine in the womb. "What we actually found is that the effects of cocaine on these child outcomes were quite subtle," Conradt says. "Cocaine was probably a proxy for the type of environment in which the kids were raised."

The researchers found that studies of newborns with NOWS produced inconsistent results. Some showed differences in behavior between newborns exposed to buprenorphine versus those exposed to methadone. Both buprenorphine and methadone are given as treatments for opioid addiction in adults, with buprenorphine approved to treat addiction in pregnant women. Although some studies showed decreased NOWS symptoms in buprenorphine-exposed newborns, other studies found no significant differences between the two groups of newborns.

"Because the data were so tenuous and the findings were so inconsistent, we didn't feel comfortable drawing a conclusion," Conradt says. "So it's not clear what the effects of prenatal opioid exposure are at birth."

Infancy

The researchers found 21 studies looking at the development of children up to 2 years of age after prenatal opioid exposure. Conradt says that many of the studies had small numbers of children in the study, which makes it more difficult to tell whether the effects seen in the study are really due to opioid exposure or could be due to other confounding factors. One study had a sufficient size to control for confounding factors, Conradt says, with 131 children. That study found many null effects of opioid exposure on cognitive and behavioral outcomes. "We felt a little bit more comfortable saying that there may not be major effects of prenatal opioid exposure in infancy after controlling for these relevant confounders," Conradt says.

Two years and beyond

Conradt found some of the same inconsistent results in the 27 studies that looked at cognitive development beyond age 2, with some studies finding significant effects in IQ and language ability, and some finding no significant effects. But studies of behavior were more consistent. Children exposed to methadone had higher fear, aggression and anxiety, and a NOWS diagnosis was associated with lower attention. Conradt says it's not surprising that behavioral effects would emerge as children get older. "As children age, they're more challenged," she says. "They have to pay attention at school, they have to sit still, they have to control their behavior. It's not surprising that kids exposed to methadone in the womb may have a harder time with those skills."

But it's still difficult, Conradt says, to determine whether these behavior effects are directly due to opioid exposure, to the children's environment or interaction between the two over time.

Moving forward

One of the main takeaways from Conradt's study is that the existing body of work is hampered by small sample sizes and abundant confounding factors that could obscure the true effects of the opioid exposure. Conradt is part of a program that aims to resolve these issues. It's called the Environmental Influences on Child Health Outcome program, abbreviated ECHO, a nationwide research program supported by the NIH to enhance child health. It's a seven-year, 71-cohort study to examine what environmental factors before and after birth affect children's developmental outcomes.

"We have the opportunity to collect data on over 50,000 children across hundreds of different sites across the country, and tracking their outcomes in a systematic and rigorous manner," Conradt says. U researchers Joe Stanford, Christy Porucznik and Angelo Giardino are principal investigators of the NIH ECHO pediatric cohorts in Utah. In the future Conradt, an ECHO investigator, and others will utilize the data as it becomes available to continue working toward understanding what prenatal opioid exposure means for the future of a growing generation of children.

CLEVELAND, Ohio (August 28, 2019)--For years, women have been told that weight gain could lead to heart disease. A new study indicates that it is the location of the fat that matters most, with abdominal fat representing the greatest harm and not overall body mass index (BMI) when assessing risk for coronary artery disease (CAD). Results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Because CAD remains the leading cause of death worldwide, there is tremendous attention given to its modifiable risk factors. Estrogen protects women's cardiovascular systems before menopause, which helps explain why the incidence of CAD in premenopausal women is lower than in men. However, as women's estrogen levels decline during and after menopause, the incidence of CAD in postmenopausal women outpaces similarly aged men.

Obesity has long been known as a risk factor for CAD because it causes endothelial cell dysfunction, insulin resistance, and coronary atherosclerosis, among other problems. It also is often accompanied by other cardiovascular risk factors, such as hypertension and diabetes. In the past, it has been suggested that overall obesity (which is often defined by BMI) is a primary risk factor. Few studies have attempted to compare the effect of overall obesity versus central obesity, which is typically described by waist circumference and/or waist-to-hip ratio.

The results of this new study of nearly 700 Korean women, however, demonstrated that the presence of obstructive CAD was significantly higher in women with central obesity. No significant difference was identified based on BMI, indicating that overall obesity was not a risk factor for obstructive CAD. These results are especially relevant for postmenopausal women because menopause causes a change in body fat distribution, especially in the abdominal area.

Findings were published in the article "Association between obesity type and obstructive cardiovascular disease in stable symptomatic postmenopausal women: data from the KoRean wOmen'S chest pain rEgistry (KoROSE).

"The findings of this study are consistent with what we know about the detrimental effects of central obesity. Not all fat is the same, and central obesity is particularly dangerous because it is associated with risk for heart disease, the number one killer of women. Identifying women with excess abdominal fat, even with a normal BMI, is important so that lifestyle interventions can be implemented," says Dr. Stephanie Faubion, NAMS medical director.

Since its approval in 1995, the opioid tramadol (marketed as ConZip and Ultram) has become a widely prescribed remedy for osteoarthritis and other painful indications, in part because it presents a lesser risk for some side effects and has a lower abuse potential when compared to other opioids. It is currently ranked among the top five prescribed opioids and top 60 prescribed medications in the country.

But as tramadol has grown in popularity so too have documented cases of adverse effects among its users. In a new paper, published August 28, 2019 by Scientific Reports, researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego show that patients who take tramadol are at greater risk for developing hypoglycemia, or abnormally low blood sugar.

The research team, led by senior author Ruben Abagyan, PhD, professor of pharmacy, analyzed more than 12 million reports from the FDA Adverse Effect Reporting System (FAERS) and Adverse Event Reporting System (AERS) databases, which chronicle voluntary reports of adverse effects while taking a medication. The period studied ranged from January 2004 to March 2019.

"The impetus was the recent dramatic surge in tramadol popularity and prescriptions," said first author Tigran Makunts, PharmD, a researcher in Abagyan's lab. "We wanted to have an objective data-driven look at its adverse effects and bumped into a dangerous, unlisted and unexpected hypoglycemia."

Recognized adverse drug reactions associated with tramadol include dizziness, nausea, headaches and constipation -- all common side effects of opioids. More serious but rarer adverse drug reactions include serotonin syndrome and increased seizure risk. The link to hypoglycemia is relatively new, though it had been previously suggested by case studies and animal model testing.

Hypoglycemia is often related to the treatment of diabetes, but can also occur in persons without diabetes. Untreated, hypoglycemia can lead to serious complications of its own, such as neurocognitive dysfunction, vision loss, greater risk of falls and loss of quality of life.

The researchers also looked at other widely prescribed opioids and similar acting, non-opioid medications, such serotonin and norepinephrine reuptake inhibitors (Cymbalta, Effexor XR) and NMDA receptors (ketamine and memantine). Only tramadol produced a significant risk of developing hypoglycemia in patients. In fact, there was a 10-fold greater risk of hypoglycemia using tramadol than virtually every other opioid. The only other drug identified with comparable effect was methadone, an opioid most commonly used to help persons reduce or quit addictions to heroin or other opiates.

While this study underscores an association between tramadol and hypoglycemia, a large, randomized, controlled clinical trial would be needed to definitively establish causality.

"The takeaway message is to warn physicians about the likelihood of low blood sugar (and/or high insulin content), in particular if the patient is predisposed to diabetes," said Abagyan, "and to motivate research about the unique molecular mechanism leading to that side effect. It is particularly important for tramadol or methadone that are used widely and, often, chronically."

Scientists have produced and tested, in mice, a vaccine that protects against a worrisome superbug: a hypervirulent form of the bacteria Klebsiella pneumoniae. And they've done so by genetically manipulating a harmless form of E. coli, report researchers at Washington University School of Medicine in St. Louis and VaxNewMo, a St. Louis-based startup.

Klebsiella pneumoniae causes a variety of infections including rare but life-threatening liver, respiratory tract, bloodstream and other infections. Little is known about how exactly people become infected, and the bacteria are unusually adept at acquiring resistance to antibiotics. The prototype vaccine, details of which are published online Aug. 27 in Proceedings of the National Academy of Sciences, may offer a way to protect people against a lethal infection that is hard to prevent and treat.

"For a long time, Klebsiella was primarily an issue in the hospital setting, so even though drug resistance was a real problem in treating these infections, the impact on the public was limited," said co-author David A. Rosen, MD, PhD, an assistant professor of pediatrics and of molecular microbiology at Washington University. "But now we're seeing Klebsiella strains that are virulent enough to cause death or severe disease in healthy people in the community. And in the past five years, the really resistant bugs and the really virulent bugs have begun to merge so we're beginning to see drug-resistant, hypervirulent strains. And that's very scary."

Hypervirulent strains of Klebsiella caused tens of thousands of infections in China, Taiwan and South Korea last year, and the bacteria are spreading around the world. About half of people infected with hypervirulent, drug-resistant Klebsiella die. Two types in particular - known as K1 and K2 - are responsible for 70 percent of the cases.

Rosen; senior author Christian Harding, PhD, a co-founder of VaxNewMo; first author Mario Feldman, PhD, an associate professor of molecular microbiology at Washington University and a co-founder of VaxNewMo; and colleagues decided to create a vaccine against the two most common strains of hypervirulent Klebsiella. The bacterium's outer surface is coated with sugars so the researchers designed a glycoconjugate vaccine composed of these sugars linked to a protein that helps make the vaccine more effective. Similar vaccines have proven highly successful at protecting people against deadly diseases such as bacterial meningitis and a kind of pneumonia.

"Glycoconjugate vaccines are among the most effective, but traditionally they've involved a lot of chemical synthesis, which is slow and expensive," Harding said. "We've replaced chemistry with biology by engineering E. coli to do all the synthesis for us."

The researchers genetically modified a harmless strain of E. coli, converting it into tiny biological factories capable of churning out the protein and sugars needed for the vaccine. Then they used another bacterial enzyme to link the proteins and sugars together.

To test the vaccine, the researchers gave groups of 20 mice three doses of the vaccine or a placebo at two-week intervals. Then they challenged the mice with about 50 bacteria of either the K1 or the K2 type. Previous studies had shown that just 50 hypervirulent Klebsiella bacteria are enough to kill a mouse. In contrast, it takes tens of millions of classical Klebsiella - the kind that affects hospitalized people - to be similarly lethal.

Of the mice that received the placebo, 80 percent infected with the K1 type and 30 percent infected with the K2 type died. In contrast, of the vaccinated mice, 80 percent infected with K1 and all of those infected with K2 survived.

"We are very happy with how effective this vaccine was," Feldman said. "We're working on scaling up production and optimizing the protocol so we can be ready to take the vaccine into clinical trials soon."

The goal is to get a vaccine ready for human use before the hypervirulent strains start causing disease in even larger numbers of people.

"As a pediatrician, I want to see people get immunity to this bug as early as possible," Rosen said. "It's still rare in the United States, but given the high likelihood of dying or having severe debilitating disease, I think you could argue for vaccinating everybody. And soon we may not have a choice. The number of cases is increasing, and we're going to get to the point that we'll need to vaccinate everybody."

Biocompatible gold nanoparticles designed to convert near-infrared light to heat have been shown to safely and effectively ablate low- to intermediate-grade tumors within the prostate, according to a study conducted at the Icahn School of Medicine and published in the journal Proceedings of the National Academy of Sciences. This treatment could offer patients a targeted therapy option that would preserve critical structures within the prostate, thus avoiding side effects associated with whole-gland treatment such as prostatectomies.

Prostate cancer is the second leading cause of cancer deaths in men in the United States?11 percent of men will be diagnosed with the disease in their lifetime. Removal or other whole-gland treatment of the prostate carries risks of urinary incontinence and erectile dysfunction. However, technological advances have provided clinicians with options for focal therapies with fewer complications.

In this study, researchers tested the effectiveness of AuroLase® Therapy, a treatment from medical device company Nanospectra Biosciences that is based on technology invented at Rice University by engineer and chemist Naomi Halas, PhD, and Duke University bioengineer Jennifer West, PhD. The Principal Investigator and lead author, Ardeshir Rastinehad, DO, Associate Professor of Urology, and Radiology, at the Icahn School of Medicine at Mount Sinai, invented the technique used in the clinical trial to target and treat the prostate cancer cells using a custom-built MR US fusion guided platform in collaboration with Philips Healthcare. AuroLase® uses gold-silica nanoshells (GSN), particles Dr. Halas invented that are composed of a silica core and a gold shell with a diameter of 150 nanometers. AuroShells® are designed to absorb energy from near-infrared light and convert it to heat, resulting in selective hyperthermic cell death, without affecting adjacent non-tumorous tissue. The treatment was effectively demonstrated in previous cell studies and animal models. Following treatment, the particles are cleared through the liver, while some remain sequestered in the liver and spleen. There are no known side effects.

Sixteen men aged 58 to 79 with low- to intermediate-grade prostate cancer (Gleason score of 4+3) received GSN infusion. All were diagnosed and treated at The Mount Sinai Hospital using a targeted biopsy technique called magnetic resonance-ultrasound fusion imaging, which uses MRI technology to extract a tissue sample directly from the tumor. Patients underwent GSN infusion and high-precision laser ablation, and received an MRI of the prostate 48-72 hours after the procedure, MRI-targeted fusion biopsies at 3 and 12 months, and a standard biopsy at 12 months. Patients were discharged on the same day as the procedure after several hours of monitoring.

GSN-mediated focal laser ablation was successful in 87.5 percent of lesions treated at one year of follow-up. The goal of researchers was to find an eradication of cancer cells during biopsy.

"Gold-silica nanoshells infusion allows for a focused therapy that treats the cancer, while sparing the rest of the prostate, thus preserving a patient's quality of life by reducing unwanted side effects, which could include erectile dysfunction and/or the leakage of urine," said Dr. Rastinehad.

"Mount Sinai's interventional urology program is research-driven and offers patients minimally invasive treatment therapies that improve quality of life," said Ash Tewari, MBBS, MCh, Chair of the Department of Urology at the Mount Sinai Health System and the Kyung Hyun Kim, MD Professor of Urology at the Icahn School of Medicine at Mount Sinai. "Dr. Rastinehad's gold nanoparticle research shows that patients are not only benefiting from this treatment, but also experiencing minimal side effects."

Organophosphates are among the most commonly used classes of pesticides in the United States, despite mounting evidence linking prenatal exposure to the chemicals to poorer cognition and behavior problems in children.

A new study led by University of California, Berkeley, researchers is one of the first to use advanced brain imaging to reveal how exposure to these chemicals in the womb changes brain activity.

The study, which appeared this week in the journal Proceedings of the National Academy of Sciences, used functional near-infrared imaging (fNIRS) to monitor blood flow in the brains of 95 teenagers born and raised in California's Salinas Valley, where agricultural spraying of pesticides is common.

Compared to their peers, teenagers estimated to have higher levels of prenatal exposure to organophosphates showed altered brain activity while performing tasks that require executive control, the study found.

"These results are compelling, because they support what we have seen with our neuropsychological testing, which is that organophosphates impact the brain," said Sharon Sagiv, associate adjunct professor of epidemiology at UC Berkeley and lead author on the study.

The teenagers were part of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal study examining the effects of pesticides and other environmental toxins on childhood development. The sudy was initiated by UC Berkeley investigators more than 20 years ago. Previous CHAMACOS work has linked prenatal organophosphate exposure with attention problems and lower IQ in children.

In the current study, the researchers used fNIRS to measure brain activation while teens ages 15 to 17 engaged in a variety of tasks requiring executive function, attention, social cognition and language comprehension.

The fNIRS technique uses infrared light to monitor blood flow in the outer regions, or cortex, of the brain. It provides similar information as functional magnetic resonance imaging (fMRI), but only requires a small cap of infrared light sources, rather than massive MRI tube, making it a more affordable and portable choice for research studies.

The researchers also used data from the California Pesticide Use Reporting program, which documents when and where agricultural pesticides are sprayed, to estimate their residential proximity to organophosphate application during pregnancy.

They found that teens with higher prenatal organophosphate exposure had less blood flow to the frontal cortex when engaged in tasks that test cognitive flexibility and visual working memory, and that they had more blood flow to the parietal and temporal lobes during tests of linguistic working memory.

"With fNIRS and other neuroimaging, we are seeing more directly the potential impact of organophosphate exposure on the brain, and it may be more sensitive to neurological deficit than cognitive testing," said Brenda Eskenazi, Professor of the Graduate School at UC Berkeley and senior author of the study.

Little is known about the relationship between pesticide exposure and the brain, so it's not clear why organophosphate exposure is associated with lower brain activity for some tasks and higher brain activity for others.

However, similar patterns have been observed in other conditions affecting the brain, including Type 1 diabetes, Parkinson's and Alzheimer's, said Allan L. Reiss, the Howard C. Robbins Professor of Psychiatry and Behavioral Sciences and a professor of radiology at Stanford University and co-author of the paper.

"The brain has a remarkable ability to utilize compensatory mechanisms to counteract long-term insults," Reiss said. "Higher activation may represent the recruitment and utilization of extra neural resources to address functional inefficiency related to a long-term insult, and lower activation, then, could be related to the eventual failure to recruit these resources after continued exposure or disease exhausts the brain's ability to bring compensatory responses online."

In the future, the team plans to repeat the brain imaging experiments on the more than 500 other participants in the CHAMACOS study to test if the associations hold.

OAK BROOK, Ill. - Elevated left ventricular mass, known as left-ventricular hypertrophy, is a stronger predictor of coronary artery disease-related death and heart failure than coronary artery calcium score, according to a new study published in the journal Radiology.

In the study led by Nadine Kawel-Boehm, M.D., a senior staff radiologist at Hospital Graubünden in Chur, Switzerland, a team of researchers analyzed data collected in the Multi-Ethnic Study of Atherosclerosis (MESA) sponsored by the National Heart, Lung, and Blood Institute. MESA is an ongoing, multi-center study of a diverse, population-based sample of 6,814 men and women age 45-84 with no known heart disease.

According to Dr. Kawel-Boehm, there is little research on predicting the long-term risk of cardiovascular events in ethnically diverse patients who have MRI-identified left ventricular (LV) hypertrophy, a condition in which the muscle mass of the heart's main pumping chamber is increased.

"Previous studies have used ECG or echocardiography, which have lower sensitivity in the diagnosis of LV hypertrophy, and typically follow patients for only several years," she said. "The MESA study used MRI, which is the gold standard for quantifying LV mass, and had a long follow-up of 15 years."

The researchers studied otherwise healthy individuals from the community in the MESA study. 4,988 MESA participants underwent a baseline cardiac MRI between 2000 and 2002 and participated in follow-up over a 15-year period. MRI showed that 247 participants in the study group had LV hypertrophy.

The mean age of all participants at baseline was 62 years, and 52 percent were women. Thirty-nine percent were white, 13 percent were Asian, 26 percent were African American and 22 percent were Hispanic.

At the 15-year follow-up, the research team found that 290 patients had a significant coronary heart disease (CHD) event, including 207 myocardial infarctions--or heart attacks, and 95 CHD deaths. Cardiovascular disease-related deaths occurred in 57 patients, and 215 patients had heart failure.

A statistical analysis of the data demonstrated that LV hypertrophy was an independent predictor of significant CHD events, including myocardial infarction, coronary artery disease-related death and heart failure.

According to the analysis, 22 percent of the study participants with LV hypertrophy had a significant CHD event, compared to 6 percent of participants without LV hypertrophy.

Patients with LV hypertrophy had 4.3 times the risk of coronary artery disease-related death compared to participants without LV hypertrophy. Deaths from coronary and non-coronary related cardiovascular causes were more strongly related to LV hypertrophy than to coronary artery calcium scoring done with a CT scan.

"In contrast to the widely used coronary artery calcium by CT, which measures a condition not known to regress under medical therapy, an elevated LV mass is potentially reversible under treatment," Dr. Kawel-Boehm said.

As a result of the long length of the study follow-up, Dr. Kawel-Boehm said the researchers were able to determine that the risk of cardiovascular events began to increase in participants with LV hypertrophy particularly after five years.

"Our results provide further evidence and motivation for regular follow up and management of individuals with left ventricular hypertrophy," she said. "A higher LV mass quantified by imaging may matter more in some instances than a high calcium score."