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Heart complications in patients diagnosed with bacterial pneumonia are more serious than in patients diagnosed with viral pneumonia, according to new research from the Intermountain Heart Institute at Intermountain Medical Center in Salt Lake City.

In the study of nearly 5,000 patients, researchers found that patients diagnosed with bacterial pneumonia had a 60 percent greater risk of a heart attack, stroke, or death than patients who had been diagnosed with viral pneumonia.

"We've always known pneumonia was a risk factor for a major adverse cardiac event, like a heart attack, within the first 90 days of being diagnosed," said J. Brent Muhlestein, MD, a cardiovascular researcher with the Intermountain Heart Institute at Intermountain Medical Center. "What we didn't know was which type of pneumonia was more dangerous. The results of this study provided a clear answer, which will allow physicians to better monitor patients and focus on reducing their risk of a major adverse cardiac event."

Results of the study will be presented during the American Heart Association Scientific Sessions in Chicago on Sunday, Nov. 11, at 10:30 a.m. CT.

The Intermountain Heart Institute at Intermountain Medical Center is part of the Intermountain Healthcare system based in Salt Lake City.

The study evaluated 4,792 patients diagnosed with pneumonia who were hospitalized at one of Intermountain Healthcare's 23 hospitals between January 2007 and May 2014. Each patient was followed for 90 days and tracked for non-fatal heart attacks, stroke, heart failure, or death.

Nearly 80 percent of the patients were diagnosed with bacterial pneumonia, and 34 percent (1,270 patients) of them had a major cardiovascular event within 90 days. At the same time, 21 percent of the patients were diagnosed with viral pneumonia, and 26 percent (258 patients) had a major adverse event within the 90-day window.

"The likely underlying cause is that bacterial pneumonia causes greater inflammation of the arteries compared to viral pneumonia," said Dr. Muhlestein.

When arteries become inflamed, it destabilizes the layers of plaque that have built up over the years. The unstable plaque can then break loose from the artery wall and cause a blockage, which leads to a heart attack, stroke, or death.

"The practical result of our study is that caregivers should be aware of the greater cardiovascular risks associated with respiratory infections like pneumonia, and especially bacterial pneumonia," said Dr. Muhlestein. "If a patient has been diagnosed with bacterial pneumonia, treat it aggressively and watch them closely for any signs of a heart attack or stroke. If the patient is taking medications specific to a heart condition, like high blood pressure or cholesterol, they should continue taking those prescribed medications."

People with known plaque buildup should be especially mindful of things they can do to prevent respiratory infections. Dr. Muhlestein recommends getting a flu shot, a pneumovax, practicing proper hand hygiene year-round (and especially during cold and flu season), and quitting smoking immediately.

A new study presented at the American Heart Association Scientific Session conference has found that patients with atrial fibrillation (AF) also show signs of asymptomatic brain injury.

Researchers from the Intermountain Medical Center Heart Institute in Salt Lake City enrolled 246 patients in the study: 198 with atrial fibrillation and 48 without AF. They then obtained plasma samples from Intermountain Healthcare's Intermountain Heart Collaborative INSPIRE registry and tested them for the circulating levels of four biomarkers associated with brain injury: glial specific GFAP and S100b; GDF15, a stress response marker; and neuron-specific au-protein.

They found that levels of three of those biomarkers - Tau, GDF15, and GFAP - were significantly higher in patients with atrial fibrillation. Findings from the study were presented at the American Heart Association Scientific Session conference in Chicago.

"We think patients with atrial fibrillation experience chronic, subclinical cerebral injuries," said Oxana Galenko, PhD, a molecular biologist at the Intermountain Medical Center Heart Institute, and the study's lead investigator. "It becomes absolutely critical to identify the early markers of this injury and help these patients who are at higher risk of having subsequent neurodegenerative problems, such as cognitive decline and dementia."

Atrial fibrillation is an irregular and sometimes rapid heartbeat that can lead to blood clots, stroke, heart failure, and other heart-related problems. Between 2.7 and 6.1 million Americans suffer from the condition, according to the Centers for Disease Control. It causes 750,000 hospitalizations and 130,000 deaths each year.

If people with atrial fibrillation are indeed suffering from ongoing brain injuries, they can also be at higher risk of developing everything from depression to neurodegeneration, which is the deterioration or death of the body's nerve cells, especially neurons in the brain, which could cause losses in mental function, said Dr. Galenko.

Dr. Galenko said that could be because atrial fibrillation alters blood flow through the body, including to and from the brain, which could lead to cerebral injury and disruption of the blood-brain barrier, which filters blood to and from the brain and spinal cord. If it's not working correctly, neuro-specific molecules like GFAP and Tau get into the bloodstream, which was seen in this study.

Dr. Galenko said the next step is to do the same kind of analysis on a larger group of patients. She also said recent results from the Swiss Atrial Fibrillation Cohort Study points in the same direction -- that atrial fibrillation causes brain injury. In the study, researchers performed MRIs on atrial fibrillation patients and found that 41 percent showed signs of at least one kind of a silent brain damage.

She believes a blood test would be the way to move forward if a method was developed to see which atrial fibrillation patients are also experiencing brain injury, for the simple reason that it's a lot cheaper and easier to do than an MRI.

"At this stage, we're at the very beginning of studying this link, but it's a step forward toward addressing the problem," she said.

A new study presented at the American Heart Association Scientific Session conference found that testing a patient's coronary calcium levels is a better predictor of blocked coronary arteries at risk for a heart attack and the need for revascularization than standard risk-assessment equations used in medical practice today.

"With coronary calcium, we're looking at a marker indicating the actual presence of anatomic disease -- we're not just looking at probabilities of disease based on a patient's standard risk factors," said Jeffrey L. Anderson, MD, a cardiologist and cardiovascular researcher at the Intermountain Medical Center Heart Institute in Salt Lake City. "The risk factors are worth knowing, but they don't tell whether or not you actually have the disease."

Cardiovascular disease remains the greatest cause of morbidity and mortality in the United States, and determining who's most at risk continues to be suboptimal, said Dr. Anderson.

Two-thirds of Americans with cardiovascular disease come from the very large, and what's traditionally been considered the low-risk portion of the population based on standard risk factors, which means a lot of at-risk people are missed during screenings.

In the new study, researchers at the Intermountain Medical Center Heart Institute, which is part of the Intermountain Healthcare system, identified 1,107 symptomatic patients who presented to the healthcare system without any known coronary artery disease and who had a PET-stress test to measure coronary flow, conducted as part of their diagnostic evaluation.

The PET/CT test also enabled a coronary calcium score to be measured. Based on the coronary calcium score and standard risk factors documented in their medical records, three different atherosclerotic cardiovascular disease risk scores were calculated: the standard Pooled Cohort Equation (based on traditional risk factors), the Multi-Ethnic Study of Atherosclerosis (MESA) Risk Score (which combines coronary calcium and traditional risk factors), and the Coronary Calcium Score alone

Researchers tracked those patients to identify who, based on PET scan results suggesting a blocked artery, went on to revascularization (a coronary stent or bypass surgery) and who had a subsequent heart attack or died during the subsequent two years.

They found that risk equations that included coronary artery calcium measurements, i.e., the MESA Score and the Coronary Calcium Risk Score, were better able to predict the presence of symptomatic coronary artery disease requiring revascularization than the Pooled Cohort Equation, which relies only on standard risk factors such as age, gender, blood pressure, and cholesterol measurements.

However, after the PET-scan results were acted upon, all three equations were only moderately successful in determining who over two years of follow-up would go on to die or have a heart attack. Noteworthy though was that of the 29 patients who showed no coronary artery calcium, none had any major heart problems in the time-period tracked.

Researchers presented results from the study at the American Heart Association's 2018 Scientific Session in Chicago.

"Calcium in the artery doesn't tell you the extent of soft plaque, but it does mark that disease is present," Dr. Anderson said. "These results tell us that coronary calcium adds importantly to probability estimates."

He also said the cost of coronary calcium screening is low, in the range of $100 or less, and should be considered in the future as part of routine medical care after age 50 for men and 55-60 for women.

"We accept that mammograms should be done for women and colonoscopies should be done for everybody at a certain age, and they're much more expensive than a calcium scan," he said.

Dr. Anderson hopes the findings lead to coronary calcium tests becoming more accepted and covered by medical insurance as a means to better predict who is at coronary risk, which not only will get high-risk patients into treatment earlier, but also keep patients who aren't truly at risk from being overtreated.

BIRMINGHAM, Ala. - As many as 300,000 United States service members deployed to Iraq and Afghanistan since 2001 have suffered traumatic brain injury due to explosions. The vast majority of these blast-induced traumatic brain injuries, or bTBIs, were classified as mild.

Unlike severe or moderate bTBIs, a mild bTBI shows no overt brain injury, such as bleeding, hematomas or bruising, and people with a mild bTBI do not lose consciousness or show concussion symptoms. Nevertheless, these injuries can eventually lead to cognitive impairment, loss of attentional function, drug addiction, and anxiety or depressive disorders.

Using a rat model of bTBI, University of Alabama at Birmingham researcher James Bibb, Ph.D., and colleagues show how even mild exposure to a single blast shock wave is able to induce small but potentially very meaningful pathogenic effects that accumulate with time.

These effects, detected at the microscopic level, included microvascular damage, injury to nerve axons and signs of neuroinflammation in various brain regions. Brain function also changed, as shown by impaired short-term synaptic plasticity.

The single mild blast also activated biochemical pathways that are associated with stroke and neurodegenerative diseases, including Alzheimer's. These included cleavage of a protein called spectrin that helps form the cytoskeleton of neurons and other cells.

"Importantly," Bibb said, "several of these effects were not detected immediately or in the first few days after injury, but developed over a longer period of time, up to 21 days after the blast had occurred."

"The implications of these findings," he said, "are that serious brain injuries may not immediately cause detectible symptoms, and that this should be considered carefully in any recovery plan that is geared toward returning individuals, sports players or soldiers to environments of risk for secondary insults."

HOUSTON - (Nov. 9, 2018) - People who have recently lost a spouse are more likely to have sleep disturbances that exacerbate levels of inflammation in the body, according to new research from Rice University and Northwestern University. These elevated levels of inflammation may increase risk for cardiovascular illness and death.

The study, "Bereavement, self-reported sleep disturbances and inflammation: Results from Project HEART," was recently published in Psychosomatic Medicine. It compared the self-reported sleep habits of recently widowed people to a control group. Both groups had sleep disturbances, such as insomnia.

The researchers found that the link between sleep disturbances and inflammation was two to three times higher for the bereaved spouses. Inflammation was measured by the level of proinflammatory cytokines, which are designed to be short-term fighters of disease but are linked to long-term risk for health problems including cardiovascular disease.

Corresponding author Diana Chirinos, a research assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine who began examining the topic as a Rice Academy postdoctoral fellow in Rice's Department of Psychological Sciences, said the study suggests that these bereaved individuals are more susceptible to the negative health effects of poor sleep.

"The death of a spouse is an acutely stressful event and they have to adapt to living without the support of the spouse," she said. "Add sleep disturbance to their already stressful situation and you double the stressor. As a result, their immune system is more overactivated."

Chirinos said she and her fellow researchers already knew widowed individuals had higher levels of inflammation. Prior work revealed that in the first six months after the loss of a spouse, widows and widowers are at a 41 percent higher risk of mortality, and 53 percent of this increased risk is due to cardiovascular disease. However, they wanted to find the specific cause.

"Now we know it's not the grief itself; it is the sleep disturbance that arises from that grief," Chirinos said.

Chris Fagundes, an assistant professor of psychological sciences at Rice and the principal investigator for Project HEART, said the finding is another revelation in the study of how human behaviors and activities impact inflammation, and it adds to a growing body of work about how bereavement can affect health. His initial work showed why people who have been widowed are at higher risk of cardiovascular problems and premature death by comparing their inflammation with matched controls.

"While working in my laboratory as a post-doctoral fellow, Diana did a great job incorporating her expertise in sleep data collection into this project," he said.

Ultimately, the researchers hope the findings will help to design better health interventions for those suffering from loss.

The study included 101 people with an average age of 67. Half were bereaved (identified through obituaries), and the rest made up the control group.

Popping the top on house paint usually draws people to look inside the can. But Princeton researchers have turned their gaze upward, to the underside of the lid, where it turns out that pattern of droplets could inspire new ways to make microscopically small structures.

The trick comes in controlling the droplets, which form under competing influences like gravity and surface tension. A new study, published Oct. 26 in the journal Nature Communications, explains how a deeper understanding of these highly dynamic, sometimes unstable forces can be harnessed to cheaply and quickly fabricate objects that normally require a more expensive and time-consuming process.

"We've done away with the molds," said Pierre-Thomas Brun, assistant professor of chemical and biological engineering at Princeton and the principal investigator for the study. "We don't need a clean room or any fancy equipment, so engineers have much more freedom in the design process."

Using a silicone common in medical devices, the team poured a thin liquid film over the surface of a plate, about the size of a compact disc, which they then flipped upside down for several minutes while the film cured. Without intervention, the liquid silicone congeals into an irregular array of droplets -- much like the paint under a lid. But by etching the plate with mathematical precision, using lasers to cut the marks, the researchers "seeded" the droplets into a lattice of perfect hexagons, each with a uniform dimension.

"Gravity wants to pull the fluid down," said Joel Marthelot, postdoctoral research associate at Princeton and lead author on the paper. "Capillary forces want the surface to deform minimally. So there is a competition between these two forces, which gives rise to the length scale of the structure."

More sophisticated versions of the experiment used a centrifuge in place of gravity, which allowed the team to vary the size of the drops with an indefinite range. Instead of plates, in this version they used plastic cylinders that look like clear hockey pucks. The excess fluid spun off and left their predictable pattern of cured drops. The technique worked down to the limit of their machinery, which produced a lattice of structures that were each around 10 microns, a fraction of the width of a human hair. The structures, which are prototypes, simulate the kinds of soft lenses that are a common part in smartphones.

"The faster it spins, the smaller the drops," Marthelot said, noting that they could make structures even smaller than what they had achieved so far. "We don't really know the limit of our technique. Only the limit of our centrifuge."

According to Brun, the kinds of mechanical instabilities that cause this behavior are usually regarded by engineers as a kind of nemesis. They are the physical thresholds that determine weight loads or heat capacities. "In this case," he said, "we took advantage of something that is normally seen as bad. We tamed it and made it functional by turning it into a pathway to fabrication."

The technique can be easily expanded to large-scale manufacturing, the researchers said. As their methods evolve, they plan to create biomimetic devices, like an inflatable compound lens that mimics the eye of an insect, or soft robots that can be used in medical technologies.

"One can envision a wide range of potential future application," said Jörn Dunkel, associate professor of mathematics at the Massachusetts Institute of Technology, "from drag-reducing or superhydrophobic surfaces to micro-lenses and artificial ciliary carpets."

Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women, led in the UK by Queen Mary University of London.

The research, using data from Sweden, finds that women who chose to participate in an organised breast cancer screening programme had a 60 per cent lower risk of dying from breast cancer within 10 years after diagnosis, and a 47 per cent lower risk of dying from breast cancer within 20 years after diagnosis.

The authors say that this benefit occurs because screening detects cancers at an earlier stage, meaning that they respond much better to treatment.

The study was co-authored and funded by the American Cancer Society and appears in the American Cancer Society's peer-review journal Cancer.

In the UK, mammography screening is offered to all women aged 50-70 through the NHS Breast Screening Programme, with participation rates averaging more than 70 per cent but varying dramatically across the country, with lower rates in poorer, inner-city areas.

Senior author Professor Stephen Duffy from Queen Mary University of London said: "Recent improvements in treatments have led to reduced deaths from breast cancer. However, these new results demonstrate the vital role that screening also has to play, giving women a much greater benefit from modern treatments. We need to ensure that participation in breast screening programmes improves, especially in socio-economically deprived areas."

The study involved 52,438 women aged 40 to 69 years in the county of Dalarna, Sweden, during 39 years of the screening era (1977-2015). All patients received stage-specific treatment according to the latest national guidelines, irrespective of the mode of detection.

The investigators, led by Laszlo Tabar, M.D., of Falun Central Hospital in Sweden, used a new method to improve the evaluation of the impact of organised mammography screening on death from breast cancer, by calculating the annual incidence of breast cancers causing death within 10 years and within 20 years after breast cancer diagnosis.

An enzyme known to help our liver get rid of ammonia also appears to be good at protecting our retina, scientists report.

Our retina, which captures light and converts it into neural signals that go to the brain so we can see, can be damaged or destroyed by conditions that reduce blood flow like diabetes, glaucoma or hypertension.

"We are trying to figure out what we can do to ameliorate that damage, to lessen the initial injury, and promote better recovery," says Dr. Ruth B. Caldwell, cell biologist, in the Vascular Biology Center at the Medical College of Georgia at Augusta University.

Caldwell and her colleagues have the first evidence that the enzyme arginase 1 may do both by suppressing inflammation produced by big white blood cells called macrophages.

Their findings indicate that arginase 1 therapy, which is already in clinical trials for cancer, could provide a novel strategy for this potentially blinding problem, they report in the journal Cell Death & Disease.

Macrophages are known to move in to an area damaged by disease or injury and clean up debris, even consume invaders like bacteria, but they also have a role in regulating inflammation.

M1 macrophages are generally thought to promote inflammation and M2s are more associated with collagen production, wound healing and repair. When inflammation isn't present, the majority of your macrophages are likely M2s, which make arginase 1, says Caldwell, the study's corresponding author.

"Basically when we remove arginase 1, the macrophages are more inflammatory, more damaging, and when we add it back, they are less inflammatory, more reparative," says Dr. Abdelrahman Y. Fouda, postdoctoral fellow in Caldwell's lab and the study's first author.

The study was the first to look at the role of arginase 1 in ischemic retinopathy using a common model called ischemia reperfusion injury, in which blood flow is removed then restored, which, like ischemic retinopathy, also induces destructive inflammation, oxidative stress and resulting damage to neurons and blood vessels.

There are currently no effective therapies for the neurovascular injury of ischemic retinopathy.

For their studies, the scientists looked at normal mice as well as those with arginase 1 knocked out bodywide, specifically from macrophages or from the endothelial cells that line blood vessels.

The import of arginase 1 on retinal health in the face of an ischemic injury was clear both when it was removed and when it was added.

Deleting the enzyme from the endothelial cells had no effect, but without it, macrophages produced a bigger inflammatory response to lipopolysaccharide, a component of the membrane of gram-negative bacteria.

Removing arginase 1 from macrophages generally worsened retinal injury, retinas became thinner and distorted and more neurons were lost, suggesting a major, protective role for macrophages containing arginase 1, the scientists say.

When they administered a more stable but still human grade of the enzyme, called pegylated arginase 1, it reduced inflammation and subsequent retinal damage following reperfusion injury in normal mice.

Pegylated arginase 1 already has been shown to be safe and of some benefit in early trials of advanced and highly lethal liver cancer. In the case of cancer, it appears to reduce the availability of the amino acid L-arginine, which arginase regularly scarfs up and which some cancers must have, so they die, says Dr. William Caldwell, pharmacologist, retired chair of the MCG Department of Pharmacology and Toxicology and study coauthor.

In the eye, while they don't yet know if adding arginase 1 really converts M1s to M2s, they definitely see less destructive inflammatory response in the retina.

"Let's just say they behave differently," Ruth Caldwell says of these immune cells that show up presumably to help. There also are likely other benefits when arginase 1 shows up since it also produces things like polyamines, compounds that are known to be good for neurons, she says.

Like macrophages, arginase has two forms, which also appear to have polar opposite effects. In the face of ischemic retinopathy, when macrophages become pro-inflammatory, they increase their level of arginase 2 and decrease levels of arginase 1.

The MCG scientists have found that deleting arginase 2 decreases cell death by inflammation, while deleting arginase 1 increases it, prompting upregulation of damaging factors like tumor necrosis factor alpha and inducible nitric oxide synthase, or iNOS.

While nitric oxide is generally considered a good thing, iNOS occurs in inflammation, producing very high levels that can contribute to oxidative stress and illustrating the need for balance, William Caldwell says.

The Caldwells are co-principal investigators on a new $1.5 million National Eye Institute grant that is enabling them to look further at the impact of both arginases when the disease has become chronic and treatment is needed for extended periods as a patient likely would.

They want to know whether in this scenario administration of pegylated arginase 1 also has undesirable effects like raising blood pressure.

As with most things, the impact of arginase 1 is about location, says William Caldwell. Inside the lining of the blood vessels, for example, it's considered bad because it competes with nitric oxide synthase for the L-arginine it needs to make nitric oxide and keep blood vessels open.

"If in a chronic model we find bad side effects, we may need a targeted therapy to deliver arginase 1 directly to the macrophages," Fouda says. For their studies to date, the enzyme has been injected into the eye and given systemically and short term, no more than a few hours after the injury.

They also are looking further at the role of arginase 1 in neurovascular injury, whether a major way it protects, as they suspect, is by promoting reparative macrophages, and generally exploring its therapeutic potential.

They also want to know more about the impact of arginase 2, which their previous studies have shown to be a bad guy in ischemic retinopathy, but which is largely unexplored in macrophages in this scenario.

"We think they may have opposite functions and that is part of understanding the whole picture," Ruth Caldwell says. So they are now looking at what arginase 2 does in the oxygen-compromising disease states retinopathy of prematurity, which occurs in premature babies, as well as high-fat diet models like type 2 diabetes.

They have already shown that following retinal injury, arginase 2 and iNOS levels go up while arginase 1 decreases.

Turkey, peanuts and pumpkin seeds are great sources for L-arginine, which teams up with arginase to help the liver eliminate ammonia, a byproduct of the body's constant use of proteins that can be lethal if it's not regularly eliminated.

Ruth Caldwell notes that there are relatively few macrophages of any type in our eyes until damage attracts them. In their ischemia reperfusion model, they think macrophages move in from the blood.

A study from a group of Massachusetts General Hospital (MGH) investigators may reduce the concern that elevating levels of urate, an approach being investigated to treat several neurodegenerative disorders, could increase the risk of hypertension. The study authors - several of whom previously conducted a phase 2 trial finding that the drug inosine safely elevated urate levels in patients with early Parkinson disease - are reporting their most recent findings in EBioMedicine, an open-access journal published by The Lancet.

"Our study does not support a hypertensive effect from urate elevation," says Xiqun Chen, MD, PhD, of the MGH Department of Neurology, lead author of the EBioMedicine report. "It also highlights the need for a more careful evaluation of urate-lowering treatments being investigated to treat hypertension."

Animal studies have suggested that the antioxidant urate could have neuroprotective effects, and observations in human patients - associations between naturally higher urate levels and reduced risk of developing Parkinson disease or slower disease progression - led to initiation of the two-year, phase 2 SURE-PD clinical trial, led by MGH neurologist Michael Schwarzschild, MD, PhD, senior author of the current study. The encouraging results of that trial, which enrolled 75 newly diagnosed Parkinson disease patients with relatively low urate levels, led to the initiation of the larger SURE-PD Phase 3 trial, which is currently underway.

But because significant evidence has suggested that higher urate is associated with hypertension, the team took a closer look at any potential effects on blood pressure among participants in the phase 2 SURE-PD trial. Among all three groups of participants - those receiving doses producing mild or moderate urate elevation or those receiving a placebo - there were no significant differences in blood pressure readings taken before, during or after the 18- to 24-month study period.

Those findings were further supported by experiments in mouse models genetically engineered to have either reduced urate or mild or moderate urate elevation. Those studies found no association of altered urate levels with significant differences in blood pressures between any of the genetically engineered mice and genetically unaltered control animals. In addition, the use of blood-pressure-manipulating agents had similar effects both on animals with elevated urate and on the controls, adding additional support to a lack of connection between urate levels and blood pressure.

"Together with the original report on the SURE-PD trial, this study provides strong evidence that long-term administration of oral inosine can be generally safe in patients with early Parkinson disease." says Chen, who is an assistant professor of Neurology at Harvard Medical School (HMS). "Although those SURE-PD participants were otherwise healthy with no obvious cardiovascular or renal disease, these findings may not be generalized to all patients. More studies are needed to definitively determine the role of urate in hypertension - including the potential of the urate-lowering drugs currently being investigated. Meanwhile, we are taking advantage of the current phase 3 inosine trial to monitor any possible risks of urate elevation in a larger group of patients."

An investigational oral antibiotic called zoliflodacin was well-tolerated and successfully cured most cases of uncomplicated gonorrhea when tested in a Phase 2 multicenter clinical trial, according to findings published today in the New England Journal of Medicine. The National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, sponsored the clinical study.

Gonorrhea is a common sexually transmitted disease (STD) that affects both men and women, particularly young people ages 15 to 24 years. Gonorrhea is the second most commonly reported notifiable disease in the United States. In 2017, more than 550,000 cases of gonorrhea were reported in the United States. If untreated, gonorrhea infection can lead to pelvic inflammatory disease, ectopic pregnancy, infertility, and an increased risk of HIV infection. Pregnant women can pass the infection to their babies, who can become blind or develop life-threatening infections as a result.

Gonorrhea is caused by the bacterium Nesseria gonorrhoeae, which has progressively developed resistance to each of the antimicrobials used to treat it. As a result, in 2015, the U.S. Centers for Disease Control and Prevention revised gonorrhea treatment guidelines to recommend dual therapy with injectable ceftriaxone and oral azithromycin to reduce the emergence of resistance to ceftriaxone.

Zoliflodacin (formerly known as ETX0914 and AZD0914), developed by Entasis Therapeutics based in Waltham, Mass., represents a new type of oral antibiotic that inhibits DNA synthesis in a different way than currently approved antibiotics.

"The rate of reported gonorrhea cases in the United States has increased 75 percent since the historic low in 2009, and antibiotic resistance has considerably reduced the number of treatment options for this disease," said NIAID Director Anthony S. Fauci, M.D. "These encouraging research findings published today suggest that zoliflodacin has the potential to be a useful and easy-to-administer oral antibiotic for treating gonorrhea."

The study took place from November 2014 through December 2015 and was led by Stephanie N. Taylor, M.D., of Louisiana State University Health Sciences Center in New Orleans. Study investigators recruited patients from sexual health clinics there and in Seattle; Indianapolis, Indiana; Birmingham, Alabama; and Durham, N.C. The trial enrolled 179 participants (167 men and12 non-pregnant women) ages 18 to 55 years with either symptoms of uncomplicated urogenital gonorrhea, untreated urogenital gonorrhea or sexual contact with someone with gonorrhea within 14 days before enrollment. Participants were randomly selected to receive either a single 2 or 3-gram dose of oral zoliflodacin or a 500-milligram (mg) dose of injectable ceftriaxone. Among the 117 per-protocol participants who were evaluated six days after treatment, 98 percent (48 of 49 participants) of those who received the 2-gram zoliflodacin dose, 100 percent (47 of 47 participants) of those who received the 3-gram dose, and all (21 of 21) of the participants in the ceftriaxone group were considered cured of their urogenital gonorrhea based on culture results.

Zoliflodacin cured all rectal gonorrheal infections (4 of 4 participants who received the 2-gram dose and 6 of 6 participants who received the 3-gram dose) as did ceftriaxone (3 of 3 participants). However, the investigational drug did not fare as well in treating patients with gonorrhea infections of the throat (pharyngeal): 67 percent of volunteers who received the 2- gram dose (4 of 6 participants) and 78 percent of those who received the 3-gram dose (7 of 9 participants) were cured. All of the participants (4 of 4) in the ceftriaxone group achieved a cure.

The investigational antibiotic was well tolerated with transient gastrointestinal upset the most commonly reported adverse effect. Microbiological evaluation of post-treatment clinical isolates did not demonstrate resistance to zoliflodacin.

In March 2018, NIAID completed a study to evaluate zoliflodacin's pharmacokinetics, safety and tolerability as a single oral dose to serve as a bridge from the Phase 2 clinical trial formulation to the final formulation for Phase 3 testing. Results from that study have not yet been made public. Additionally, in September 2018 NIAID launched a Phase 1 study to evaluate the investigational drug's cardiac effects, a standard safety test for new drugs such as this.

Zoliflodacin has been awarded fast track status by the U.S. Food and Drug Administration for development as oral treatment for gonococcal infections. It is expected to begin Phase 3 testing in the Netherlands, South Africa, Thailand and the United States next year.

Smoking, diabetes and high blood pressure increase the risk of a heart attack more in women than in men, new research from The George Institute for Global Health at the University of Oxford has found.

The study, of 472,000 participants aged 40-69, found that smoking, diabetes, high blood pressure and having a BMI ?25 puts both men and women at increased risk of having a heart attack. However, while male current smokers have over twice the risk of a heart attack than men who have never smoked, female smokers were found to have over three times the risk of women who have never smoked, giving them a so-called 'excess risk'.

An excess risk was also found among women with high blood pressure, and Type I and Type II diabetes, but not with a high BMI.

"Overall, more men experience heart attacks than women. However, several major risk factors increase the risk in women more than they increase the risk in men, so women with these factors experience a relative disadvantage," said Dr. Elizabeth Millett, Epidemiologist at The George Institute UK, who led the research using data from the UK Biobank.

The excess risk of heart attack among people smoking 20 or more cigarettes per day when compared with people of the same sex who have never smoked was twice as big in women as in men. High blood pressure was associated with a more than 80% higher relative risk in women than in men, while Type I diabetes was associated with an almost three times higher relative risk, and Type II diabetes a 47% higher relative risk in women than in men.

Heart attack occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart tissue. Patients experiencing heart attack may have symptoms of chest pain, shortness of breath, and pain in their arms, back, neck, jaw or stomach. Additional symptoms, more common in women, are unusual tiredness, dizziness, cold sweats, and nausea or vomiting.

Researchers also looked at the risk of heart attack associated with ageing. While the increase in risk posed by factors such as smoking and high blood pressure lessened in both sexes as they grew older, the additional excess risk experienced by women was found to persist with ageing.

In the UK, nearly one in seven men and one in twelve women die from coronary heart disease, the leading cause of heart attacks [1]. Over time, population ageing, coupled with the increasing prevalence of unhealthy lifestyles, is expected to result in women having a more similar overall rate of heart attack to men, which is likely to impose a significant additional burden on society and health resources.

"These findings highlight the importance of raising awareness around the risk of heart attack women face, and ensuring that women as well as men have access to guideline-based treatments for diabetes and high blood pressure, and to resources to help them stop smoking," Dr. Millett said.

A new Journal of Economics & Management Strategy study investigates whether social media may be used as a source of information for recruiters to discriminate against job applicants.

For the study, researchers set up an experiment that involved sending more than 800 applications from two fictitious applicants who differed in their cities of origin, a typical French town (Brives-la-Gaillarde) or Marrakesh, Morocco. This information is available only on their Facebook profiles, not on the resumes or the cover letters sent to recruiters. The investigators selected job openings published in over several months in mid-2012 on the French public agency for employment website Pôle emploi.

A significant 41.7% gap between the two applicants' callback rates highlighted that personal online profiles are used by recruiters as a source of information to discriminate against applicants of foreign origin.

During the experiment, the Facebook default layout changed as Facebook introduced sub-tabs within profiles. This change reduced the salience of the information related to the applicants' language spoken. After the layout change, the difference in callback rates faded away. This suggests that the screening conducted by the employers does not go beyond the main pages of profiles. It also indicates that design choices made by online platforms, such as which information is displayed and how it is displayed, may have important consequences on the extent of discrimination.

"This study illustrates that design choices made by online platforms can dramatically affect a decision like calling back, or not, an applicant for a job interview. Internet companies should integrate this fact into their design thinking," said co-author Dr. Matthieu Manant of University of Paris-Sud.

In a Psycho-Oncology study of childhood cancer survivors, several health behaviors fell short of expectations for exercise and diet during early survivorship, and they remained sub-optimal upon reaching five years post-diagnosis.

The study followed families of children with cancer (ages 5-17 at recruitment) from diagnosis through five years. Three years and five years post-diagnosis, 82 survivors and 103 mothers of survivors completed questionnaires assessing exercise, dietary, and sleep patterns among survivors.

At three- and five-years post-diagnosis, mothers' and survivors' responses indicated that few survivors engaged in appropriate levels of low-intensity exercise, fruit/vegetable intake, and dairy consumption; however, most survivors engaged in recommended levels of high intensity exercise, fast food restriction, and sleep. Higher income was associated with decreased intake of fast food over time, whereas lower income was associated with increased intake.

"Childhood cancer survivors are at elevated risk for a multitude of conditions later in life, and greater engagement in healthy habits may be particularly important for this population," said lead author Rachel Fisher, of Nationwide Children's Hospital, in Columbus. "These findings emphasize that there is much work to be done to ensure that these survivors enjoy full, healthy lives."

In an Acta Ophthalmologica analysis of 11 relevant articles, maternal smoking during pregnancy was associated with a 46 percent increased risk that offspring will develop strabismus--one of the most prevalent eye-related diseases among children. Maternal smoking of ?10 cigarettes per day during pregnancy was linked with a 79 percent increased risk of strabismus in offspring.

In children with strabismus, the eyes do not properly align with each other. This can contribute to visual impairment and emotional problems.

"Maternal smoking during pregnancy is an important public health problem, particularly in developed countries, and its effect on offspring eye health deserves our attention," said senior author Dr. Zuxun Lu, of the Huazhong University of Science and Technology, in China.

A new study has examined whether managing weight during pregnancy might affect children's bone mass.

In the Journal of Bone and Mineral Research study, investigators analyzed prospective data from 2,167 mother-child pairs from Portugal. In under/normal weight mothers, weight gain during pregnancy was associated with slightly increased bone mass at 7 years of age in children, while in overweight/obese mothers, no beneficial effect of weight gain on bone mass was observed.

Given the well-known adverse implications of excessive weight gain during pregnancy for both the mother and child on various aspects of health, following the current recommendations on pregnancy weight gain should not have consequences on children's skeletal health.

"Until recently, it was a widely held scientific belief that any weight gain from the mother during pregnancy would have a beneficial effect on children's bone mass. Our study results corroborate that there is no benefit in gaining weight above the US Institute of

Medicine recommendations for pregnancy weight gain for children's bone mass, in both normal and overweight women prior to pregnancy," said lead author Dr. Teresa Monjardino, of the Universidade do Porto, in Portugal.