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The results of a study presented at the Annual European Congress of Rheumatology (EULAR 2018) demonstrates increased levels of gum disease, and disease-causing bacteria, in individuals at risk of rheumatoid arthritis (RA).1

"It has been shown that RA-associated antibodies, such as anti-citrullinated protein antibodies, are present well before any evidence of joint disease. This suggests they originate from a site outside of the joints," said Dr Kulveer Mankia of Leeds Institute of Rheumatic and Muscoskeletal Medicine and the Leeds Biomedical Research Centre (study author). "Our study is the first to describe clinical periodontal disease and the relative abundance of periodontal bacteria in these at-risk individuals. Our results support the hypothesis that local inflammation at mucosal surfaces, such as the gums in this case, may provide the primary trigger for the systemic autoimmunity seen in RA."

Rheumatoid arthritis is a chronic inflammatory disease that affects a person's joints, causing pain and disability. It can also affect internal organs. Rheumatoid arthritis is more common in older people, but there is also a high prevalence in young adults, adolescents and even children, and it affects women more frequently than men.

The prevalence of gum disease is increased in patients with RA and could be a key initiator of RA-related autoimmunity. This is because autoimmunity in RA is characterised by an antibody response to citrullinated proteins and the oral bacterium Porphyromonas gingivalis (Pg) is the only human pathogen known to express an enzyme that can generate citrullinated proteins.2

"We welcome these data in presenting concepts that may enhance clinical understanding of the key initiators of rheumatoid arthritis," said Professor Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. "This is an essential step towards the ultimate goal of disease prevention."

In results from the study, dentists diagnosed clinical gum disease in significantly more at-risk individuals than in healthy controls (73% vs. 38%, p=0.02). In addition, the percentage of sites with clinical attachment level (CAL) ?2mm, pocket depth (PD) ?4mm, bleeding on probing (BOP), periodontal disease (PDD), and active periodontal disease (PDD+BOP), were all significantly greater in the at-risk individuals compared to controls (pDNA was isolated from the subgingival plaque, next to the gums, of each participant and used to measure the levels of three types of bacteria, Pg, Aggregatibacter actinomycetemcomitans (Aa) and Filifactor Alocis. Results showed that there was increased abundance of both Pg and Aa in at-risk individuals. However, in at-risk individuals, only Pg was significantly increased at healthy dental sites and was associated with the overall extent of gum disease (pThe study included 48 at-risk individuals (positive test for anti-citrullinated protein antibodies, musculoskeletal symptoms but no clinical synovitis), 26 patients with RA and 32 healthy controls. The three groups were balanced for age, gender and smoking. At-risk individuals underwent ultrasound assessment to assess for subclinical synovitis; only two (4%) were found to have ultrasound synovitis. Dentists examined six sites per tooth in each participant and a clinical consensus was agreed in each by three dentists.1

Abstract number: OP0352

Screening for abdominal aortic aneurysm - swelling of the major artery in the abdomen, which can cause sudden death if it ruptures - may not substantially reduce deaths from the condition, according to a Swedish cohort study of more than 130000 men published in The Lancet. The findings question the need for the screening, which is also conducted in the UK and USA.

In recent years, the number of cases of abdominal aortic aneurysm have decreased significantly, which may alter the benefits and harms of the screening.

In the study, the authors estimate how many deaths were avoided as a result of screening, how many people were overdiagnosed, and how many people were treated when they did not need to be.

Overdiagnosis is the detection of swelling in the artery that would never have caused symptoms in a person's lifetime, nor caused their death. This can lead to unnecessary psychological distress, and mean that people undergo needless surgery. The surgery for abdominal aortic aneurysm is a complex operation in which the swelling of the major artery in the abdomen is replaced with a graft. The surgery has a risk of serious complications such as stroke, myocardial infarction, amputation, renal failure, and even death.

Screening for abdominal aortic aneurysm is available in Sweden [1], the UK and USA, and is offered to men when they turn 65 years old. It involves an ultrasound scan of the abdomen to measure the size of the aorta. Men who have an aorta that is 30 millimetres wide or more are diagnosed with abdominal aortic aneurysm, and monitored regularly. Men with an aorta wider than 55 mm are offered preventative surgery.

The study followed 25265 men aged 65 years or older who were invited to screening between 2006-2009, and 106087 men who were not invited for screening but otherwise similar (matched control group). The researchers calculated how many men were diagnosed with an abdominal aortic aneurysm, how many underwent surgery, and how many men died from the condition. They also looked at overall trends for these factors for all men aged 40-99 years in Sweden, between 1985 and 2015.

Between 2000-2015, mortality from abdominal aortic aneurysm declined by 70% across Sweden (from 36 to 10 deaths per 100000 men aged 65-74), with rates remaining similar in men who were and were not screened. In addition, screening did not substantially reduce mortality, with an estimated two deaths avoided for every 10000 men screened six years after screening. The difference was not statistically significant.

Screening was associated with significant harm from overdiagnosis and unnecessary treatment - six years after screening, 49 in every 10000 men screened were likely to have been overdiagnosed, and 19 of these men were likely to have undergone needless surgery.

As a result, the authors conclude that abdominal aortic aneurysm screening had only a minor effect on mortality, and instead suggest that the lower mortality from abdominal aortic aneurysm may be caused by declining smoking rates. [2]

They warn that the harms of screening may outweigh the benefits, and question its continued use. They also note that many cases are identified outside of the screening programme, through opportunistic testing and identification.

"Previously, the balance between the benefits and harms of screening programmes for abdominal aortic aneurysm was unclear as the major harms had not been adequately considered. Our new findings suggest that this screening programme may be outdated, because the number of deaths from abdominal aortic aneurysm has been greatly reduced, likely due to lower smoking rates," says lead author Dr Minna Johansson, University of Gothenburg, Sweden. "As a result, the harms of this screening appear to outweigh the benefits, and our findings question the continued use of screening for abdominal aortic aneurysm in men. The results from this study are likely to be applicable to countries with similar trends in smoking rates and abdominal aortic aneurysm, which applies to many Western countries, for example the UK." [3]

The authors note some limitations, including that the follow-up of six years may not capture the full effect of screening, potentially underestimating the benefits and overestimating the harms. However, the authors do not believe that this would significantly change their conclusions.

Lastly, abdominal aortic aneurysm screening often finds other types of aneurysms, and this study does not take into account the possible benefits or harms of this.

Every cell in the body contains thousands of different protein molecules and they can change this composition whenever they are induced to perform a particular task or convert into a different cell type. Understanding how cells function depends on proteomics, the ability to measure all of the changes in a cell's protein components.

In a recent paper published in the journal Analytical Chemistry, Martin Wühr and colleagues in Princeton University's Department of Molecular Biology described an improved method to accurately count the proteins present in a cell under different circumstances.

The basic tool for counting proteins is a machine called a mass spectrometer. Cell samples can be run through this type of instrument one at a time, but this is laborious and it can be difficult to detect any changes between different samples. An alternative approach is to label all of the proteins in a particular sample with a unique "isobaric" tag. Multiple samples--up to 11--can then be mixed together and run through the mass spectrometer at the same time, with the isobaric tag functioning as an identifying barcode that tells the researcher which sample the protein originally came from. This speeds things up and makes it easier to quantify any changes in the protein composition of different samples.

"However, with the simplest version of isobaric tagging, known as TMT-MS2, there are major difficulties in distinguishing real signals from background noise," Wühr explains. "That makes the readouts unreliable and only semi-quantitative."

A more complex version of isobaric tagging, called TMT-MS3, can improve this signal-to-noise problem, but it is slower and less sensitive. Moreover, it relies on a much more expensive type of mass spectrometer beyond the reach of most researchers.

While he was a postdoc at Harvard University, Wühr developed a different approach to isobaric tagging that solved the signal-to-noise problem while remaining compatible with cheaper, widely available mass spectrometers. But the technique--known as TMTc--was not without its own problems, particularly a lack of precision that made it hard to obtain consistent results.

In their recent Analytical Chemistry paper, Wühr and two of his graduate students, Matthew Sonnett and Eyan Yeung, described an improved version of TMTc that they named TMTc+. By changing how the cell samples are prepared and altering the computer algorithm that extracts data from the mass spectrometer, Wühr and colleagues were able to address many of the limitations associated with the various methods of isobaric tagging.

"The TMTc+ method is in a kind of sweet spot compared to the other methods," Wühr says. "It provides superb measurement accuracy and precision, it's at least as sensitive as any other method, and it's compatible with around ten times more mass spectrometers than TMT-MS3."

Naturally, Wühr says, there is still room for improvement. TMTc+ only allows a maximum of 5 samples to be run at the same time, and the detection of proteins in these samples is relatively inefficient. Both of these problems can be solved by developing new types of isobaric tags. "We have to explore the chemical space of these tags and find ones that work really well," Wühr says. "To this end, we have started a collaboration with the Carell group, organic chemistry experts at the LMU Munich, and already published a proof of principle paper. Eventually, these efforts should lead to an approach that will allow researchers to count every protein in a cell as it changes its form and function."

ANN ARBOR--Umpteen books and programs are available to help new moms before and after their child is born, but the same can't be said for fathers, a new University of Michigan study found.

Research suggests that men typically rely on women for parenting knowledge and thus could benefit from encouragement to participate directly in programs and health care visits, said Joyce Lee, the study's lead author.

Despite the accumulating evidence for the benefits of father involvement, few perinatal parent educational programs have included dads.

"This disparity in service likely hinders men's involvement in important pregnancy and childbirth-related decisions," said Lee, a U-M doctoral student in social work and psychology.

Previous studies show that it's important to involve fathers in children's lives as early as possible to promote children's health and well-being. When dads participate in caretaking and activities, such as reading and active play, it supports children's development of vocabulary and positive social skills, among other things. But dads need information and support to help them engage with their children early on, and there aren't many available parenting resources targeting men. The pediatrician and obstetrician offices are often an important resource for new parents, especially through the programs that they offer.

These programs represented a total of 21 out of 1,353 studies the researchers reviewed, demonstrating the very small number of early parent education programs available to fathers. Moreover, the majority of programs lacked evidence of being effective, the researchers say.

However, the U-M study found that some of the father-inclusive parent education programs were linked to increases in father involvement, co-parenting relationships, partner relationship quality, father's mental health and father's supportive behaviors.

The researchers say that clinicians can also play a key role in promoting father involvement early on. They can acknowledge and welcome fathers at health care visits, educate fathers about the role they play in their children's early years, screen for fathers' postpartum depression, and openly discuss with fathers and mothers about the changes they are likely to experience during pregnancy and after the birth of the infant.

"Research suggests that men typically rely on women for parenting knowledge and thus could benefit from encouragement to participate directly in programs and health care visits," Lee said. "Male health care staff may be particularly effective in directly engaging fathers."

Lee says some father-inclusive perinatal educational programs are successful, such as an intervention approach involving a home visitation program add-on for fathers that targets low-income households.

Irvine, Calif., June 13, 2018 - El Niño was long considered a reliable tool for predicting future precipitation in the southwestern United States, but its forecasting power has diminished in recent cycles, possibly due to global climate change. In a study published today in Nature Communications, scientists and engineers at the University of California, Irvine demonstrate a new method for projecting wet or dry weather in the winter ahead.

"The interhemispheric teleconnection that we have discovered promises earlier and more accurate prediction of winter precipitation in California and the southwestern U.S.," said study co-author Efi Foufoula-Georgiou, UCI Distinguished Professor of civil & environmental engineering. "Knowing how much rain to expect in the coming winter is crucial for the economy, water security and ecosystem management of the region."

The researchers called the new teleconnection the New Zealand Index, because the sea surface temperature anomaly that triggers it begins in July and August in the southwestern Pacific Ocean, close to New Zealand. As the sea surface temperature in the region cools down or heats up, it causes a change in the southern Hadley cell, an atmospheric convection zone from the equator to about the 30th parallel south.

This prompts a commensurate anomaly east of the Philippine Islands, which, in turn, results in a strengthening or weakening of the jet stream in the Northern Hemisphere, having a direct influence on the amount of rain that falls on California between November and March.

"With the New Zealand Index, we can predict from late summer the likelihood of above- or below-normal winter precipitation in the southwestern U.S., with a correlation in the order of 0.7 - compared to the El Niño-Southern Oscillation technique, which has a correlation around 0.3 to 0.4," said lead author Antonios Mamalakis, a UCI graduate student in civil & environmental engineering. "Our research also shows an amplification of this newly discovered teleconnection over the past four decades."

For the study, an interdisciplinary team of scientists analyzed sea surface temperature and atmospheric pressure in 1- and 2-degree cells around the globe from 1950 to 2015.

Mamalakis said the unexpected result was the discovery of persistent sea surface temperature and atmospheric pressure patterns in the southwestern Pacific Ocean that exhibited a strong correlation with precipitation in Southern California, Nevada, Arizona and Utah.

Climate researchers have traditionally relied on a few planet-spanning oceanic and atmospheric conditions to help them forecast future rainfall. Gradual changes in sea surface temperature in vast regions of the Atlantic and Pacific oceans, jet stream-influencing high-pressure ridges over the Gulf of Alaska, and the familiar El Niño-Southern Oscillation are all players in the precipitation prediction game.

But in recent years, strongly positive El Niño conditions did not bring a lot of rain to California, as they had in the past, while the usually arid state received heavy precipitation in the winter of 2017, considered a neutral El Niño season.

"Predicting drought in the southwestern U.S. is a critical issue for food production and local economies," said Tom Torgersen, director of the National Science Foundation's Water Sustainability & Climate program, which funded the research. "The discovery of an interhemispheric bridge that affects the winter U.S. jet stream holds the promise of improved precipitation predictability and drought forecasts."

The world produces more corn by weight than any other cereal crop. Corn, also known as maize, is a staple food in many countries. But farmers growing corn face many challenges, such as drought, diseases, and pests.

For example, in sub-Saharan Africa, 20 to 80% of corn yields may be lost because of a semi-parasitic plant, Striga. In areas infested with Striga, farmers may even lose their entire crops.

In a new study, researchers from southern Africa identified several varieties of corn resistant or tolerant to Striga. Importantly, these varieties also have improved nutritional content, particularly protein.

The combination of Striga tolerance and improved nutrition is key. Farmers, as well as local populations, will benefit, says Peter Setimela, a study co-author. Setimela is a scientist at the International Maize and Wheat Improvement Centre in Harare, Zimbabwe.

Striga infestations can force small farmers in sub-Saharan and southern Africa to abandon their farms. "Striga is known to affect fields that have poor soil fertility. Its seeds can stay in the soil for more than 15 years," says Setimela. "Many small farmers can't afford to buy chemicals to control Striga. They may also be unable to buy chemical fertilizers."

Having access to varieties of corn that can tolerate Striga will benefit these farmers. They will be able to continue farming and growing corn in areas with Striga.

The improved nutritional content of these corn varieties will also help. The varieties have a wider variety of amino acids, the building blocks of protein.

"Typically, corn is poor in essential amino acids. Human and animal bodies can't make these amino acids. They have to be obtained from food," says Setimela. "Lack of essential amino acids can impair growth and development. It can also weaken the immune system."

Many rural populations depend on corn as a staple food. "But these populations often have limited access to protein sources, such as eggs, meat, and dairy products," says Setimela. "If varieties of corn can provide high-quality protein, these populations will benefit."

Setimela and colleagues tested both typical and high-protein varieties of corn for Striga resistance in the lab and field.

Controlled conditions, such as those in the laboratory, allow researchers to conduct tests that may not be possible in the field. But "ultimately, crops will be grown in farmers' fields," says Setimela. "We ensured that the results from controlled environments also apply to field conditions."

Field experiments were carried out in three locations in Zimbabwe with diverse conditions. The researchers tested eight high-protein varieties and four typical varieties of maize. They measured several plant characteristics, including yield, height, vigor, and kernel weight.

Researchers found four varieties of high-protein corn that also showed high levels of Striga tolerance and high yields.

"These varieties will provide options to farmers in areas with Striga," says Setimela. "They will improve food security and nutrition."

PHILADELPHIA -- (June 13, 2018) -- Patient age correlates with response to immunotherapy in melanoma and depleting regulatory T cells in young patients may have a therapeutic potential to enhance response in younger patients, according to research from The Wistar Institute. Study results were published online in Clinical Cancer Research.

Immune checkpoint blockade therapy has been recently approved for treatment of melanoma based on its ability to produce durable disease control. Not all patients benefit from this therapeutic approach and some responders eventually develop resistance, highlighting the need for biomarkers that could help predict patient benefit and guide therapeutic choices.

"We have shown that the characteristics of the aged tumor microenvironment in older patients promote resistance to melanoma targeted therapies, highlighting the importance of considering patient age when predicting response to therapy," said Ashani Weeraratna, Ph.D., Ira Brind Associate Professor and co-program leader of the Immunology, Microenvironment and Metastasis Program at Wistar and corresponding author of the paper.

Based on this consideration, Weeraratna and collaborators set to analyze the impact of age on response to immunotherapy. "We were initially surprised to find that older patients fare better on immune checkpoint blockade therapy," she added.

The researchers analyzed a multi-national, multi-institutional cohort of almost 500 melanoma patients treated with pembrolizumab, an anti-programmed cell death receptor-1 (PD1) checkpoint therapy. They observed a significant difference in response to treatment by age, specifically that older patients had a decreased chance of disease progression after therapy, irrespective of gender and prior treatment with targeted therapies.

This observation was confirmed in mouse models of melanoma. In fact, genetically identical tumors responded more to anti-PD1 treatment when transplanted in old mice than in young mice, suggesting that the difference is ascribable to the environment in which the tumor develops.

The researchers analyzed the immune cell composition of the old and young tumor microenvironment both in patient-derived tissues and in mouse models and found a significant decrease in tumor infiltration of regulatory T cells (Treg) with age. These cells, characterized by expression of the FOXP3 marker, suppress the anti-tumor immune response and reduce response to anticancer immunotherapy. In parallel with a decrease in the percentage of Treg cells, older age correlated with increased presence of killer CD8 T cells, which are the primary effectors in the response to immune checkpoint blockade therapy.

Based on these observations, the researchers depleted Treg cells in the young mouse model by targeting them with an antibody against CD25, which is predominantly expressed at high levels on Treg cells. Combining anti-PD1 and anti-CD25 treatment was significantly more effective than anti-PD1 alone and they obtained response rates similar to those seen in aged mice, suggesting that overcoming the immune suppression observed in the young microenvironment helps to restore sensitivity to immunotherapy.

"Our study shows that age is an important factor to consider when administering immunotherapy to melanoma patients," added Weeraratna. "A combination approach to deplete immune suppressive cells in combination with checkpoint blockade therapy might benefit younger patients, although further studies will be required to evaluate more broadly the potential immune toxicities of this approach."

CHICAGO--With aging comes deteriorating vision. At SIGGRAPH 2018, attendees will have the chance to test a new computational system that effectively mimics the natural way the human eye corrects focus, specifically while viewing objects that are closer rather than farther away.

This particular inability to focus clearly on nearby objects is called presbyopia, and everyone could have a varying degree of this problem as they age. A team of Stanford University researchers has developed a system that automatically corrects this mechanism. Dubbed Autofocals, the system externally mimics the natural accommodation response of the eye by combining data from eye trackers and a depth sensor, and then automatically drives focus-tunable lenses. While there are a variety of vision correction options to address this problem, most solutions, to date, fall short of delivering users the natural vision quality of their youth.

"A lot of presbyopes have had time to get used to their corrections, through progressive lenses, monovision, etc., but they still spent the majority of their lives being able to refocus their eyes," says Nitish Padmanaban, lead author of the study and electrical engineering PhD candidate at Stanford. "We want to restore that experience."

Padmanaban and collaborators, including Robert Konrad, PhD candidate at Stanford, and Gordon Wetzstein, assistant professor of electrical engineering and of computer science at Stanford, will demonstrate Autofocals at SIGGRAPH 2018, held 12-16 August in Vancouver, British Columbia. The annual conference and exhibition showcases the world's leading professionals, academics, and creative minds at the forefront of computer graphics and interactive techniques.

Building on previous advances made in the area of automated vision correction, Autofocals' focus-tunable eyewear for presbyopia correction incorporates eye trackers and a depth camera with a sensor fusion algorithm designed to jointly and effectively make use of both in one complete system.

The team evaluated Autofocals on 24 users, ages 51 to 81, across a set of visual performance tasks: visual acuity (sharpness of eyesight), contrast sensitivity, and letter matching. In this introductory study, users experienced better visual acuity at nearer distances when compared to monovision and progressive lenses methods, while not sacrificing 20/20 visual acuity at any distance. Monovision is the use of one contact lens that corrects only distance vision in one eye, and another lens that corrects only near vision in the other eye. Progressive lenses are popular eyewear lenses that offer focus correction at varying strengths and distances. Preliminary results also indicated that users did not experience a sizable difference with respect to contrast sensitivity and letter matching, and the majority felt the prototype worked more effectively than their own corrective lenses.

"While the technology is still in its early stages, several of the presbyopes who've tried our system genuinely wanted to have a working version for themselves," notes Padmanaban. "Vision is such an important sense for all of us that every improvement counts for a lot in terms of quality of life."

At the SIGGRAPH demo, those who suffer from presbyopia will get started by calibrating the eye trackers on the Autofocals device, after which they should be able to simply look around and have different objects automatically pop into focus. For younger attendees, a separate focus-tunable lens will be made available to them so that they can experience firsthand some sense of the problem that Autofocals is attempting to address.

In future work, the researchers might explore improving the eye-tracking component; specifically, digging deeper into developing a calibration-free or calibration-on-the-fly eye-tracking capability. Current user experience now entails having to calibrate the eye trackers each time the device is worn or when they slip off the wearer's face, for example. Other improvements could be made to the device itself, with respect to design aesthetics and practical use.

"One could imagine that as this technology improves," adds Padmanaban, "you could have a single pair of glasses for your entire life."

A theorized but never-before detected property of quantum matter has now been spotted in the lab, a team of scientists reports.

The team proved that a particular quantum material can demonstrate electrical dipole fluctuations - irregular oscillations of tiny charged poles on the material - even in extremely cold conditions, in the neighborhood of minus 450 degrees Fahrenheit.

The material, first synthesized 20 years ago, is called k-(BEDT-TTF)2Hg(SCN)2 Br. It is derived from organic compounds, but behaves like a metal.

"What we found with this particular quantum material is that, even at super-cold temperatures, electrical dipoles are still present and fluctuate according to the laws of quantum mechanics," said Natalia Drichko, associate research professor in physics at the Johns Hopkins University.

"Usually, we think of quantum mechanics as a theory of small things, like atoms, but here we observe that the whole crystal is behaving quantum-mechanically," said Drichko, senior author of a paper on the research published in the journal Science.

Classical physics describes most of the behavior of physical objects we see and experience in everyday life. In classical physics, objects freeze at extremely low temperatures, Drichko said. In quantum physics - science that has grown up primarily to describe the behavior of matter and energy at the atomic level and smaller - there is motion even at those frigid temperatures, Drichko said.

"That's one of the major differences between classical and quantum physics that condensed matter physicists are exploring," she said.

An electrical dipole is a pair of equal but oppositely charged poles separated by some distance. Such dipoles can, for instance, allow a hair to "stick" to a comb through the exchange of static electricity: Tiny dipoles form on the edge of the comb and the edge of the hair.

Drichko's research team observed the new extreme-low-temperature electrical state of the quantum matter in Drichko's Raman spectroscopy lab, where the key work was done by graduate student Nora Hassan. Team members shined focused light on a small crystal of the material. Employing techniques from other disciplines, including chemistry and biology, they found proof of the dipole fluctuations.

The study was possible because of the team's home-built, custom-engineered spectrometer, which increased the sensitivity of the measurements 100 times.

The unique quantum effect the team found could potentially be used in quantum computing, a type of computing in which information is captured and stored in ways that take advantage of the quantum states of matter.

Boston (June 10, 2018) - Results from a new clinical study have confirmed the safety and tolerability of using bacteria-specific viruses known as bacteriophages to eliminate disease-causing bacteria in the gut. The new treatment could be used in place of antibiotics to rid the gut of harmful bacteria and promote the growth of beneficial bacteria that are known to enhance gastrointestinal health, immune function and anti-inflammatory processes.

"People taking antibiotics can develop resistance and experience gastrointestinal distress since antibiotics kill both bad and good bacteria in the gut," said study co-investigator, Taylor C. Wallace, Ph.D., principal and CEO of the Think Healthy Group Inc. and an adjunct professor in the Department of Nutrition and Food Studies at George Mason University. "Using viruses that infect only specific types of bacteria spares the many good bacteria in the gut, which are linked to numerous long-term beneficial health outcomes. We have shown for the first time that bacteriophage treatment has no apparent side effects, at least with short-term use."

Wallace will present the results from the Bacteriophage for Gastrointestinal Health (PHAGE) Study -- the first clinical study in the Western hemisphere to provide patients with bacteriophages -- at the American Society for Nutrition annual meeting, Nutrition 2018, held June 9-12, 2018 in Boston.

Bacteriophages can be used to selectively combat specific microorganisms in people without causing any type of infection or disrupting the body's microbiome as a whole. In addition to treating bacteria-related gastrointestinal illnesses, Wallace and study co-investigator Tiffany Weir, Ph.D., of Colorado State University are interested in using bacteriophages as dietary supplements to help restore balance to the bacteria that live in the gut of people with metabolic syndrome, which is known to shift gut bacteria to a more pathogenic and inflammatory state.

The PHAGE study included 31 people who reported significant gastrointestinal distress at the beginning of the study, but who were not diagnosed with any specific gastrointestinal disorder. Study participants were assigned to either a placebo or treatment group for the first four weeks of the study, followed by a two-week washout period and an additional four weeks on the opposite treatment. The treatment group received four bacteriophage strains that specifically eliminate E. coli, a pathogen that can contribute to gastrointestinal irregularities and stomach upset.

The researchers report that study participants tolerated the bacteriophage treatment extremely well, with no adverse events reported during the four weeks of treatment. During the bacteriophage treatment, they observed significant decreases in interleukin 4, an inflammatory marker often associated with allergic response. There were also changes in differential abundance of several other gut bacterial species, including reductions in Clostridium perfringens and increases in several health-promoting bacterial species. Within a small subset of individuals with two or more risk factors for metabolic syndrome, there was also an increase in beneficial Bifidobacterium spp.

The researchers say that bacteriophages might also be useful for eliminating nutritional deficiencies due to chronic diarrhea in developing countries and are seeking larger-scale support to test which strains might be best for this application. Chronic diarrhea and associated malnutrition are the second most common causes of childhood death worldwide.

Taylor C. Wallace will present this research on Sunday, June 10, during the Medical Nutrition: Interventions for the Treatment and Prevention of Nutrition-Related Diseases Session from 3- 5 p.m. in the Hynes Convention Center, Room 206 (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

Please note that abstracts presented at Nutrition 2018 were evaluated and selected by a committee of experts but have not generally undergone the same peer review process required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available.

June 10, 2018 - Atlanta, GA - Researchers from GeoVax have developed a flexible "Plug and Play" technology platform that delivers single-dose vaccines that fully protect against emerging infectious diseases such as Zika, Lassa fever, and Ebola. The research will be presented at ASM Microbe, the annual meeting of the American Society for Microbiology, held from June 7th to June 11th in Atlanta, Georgia.

"Unlike other vaccine technologies currently available, which sacrifice confidence in success for speed or vice-versa, the GeoVax technology offers a true "Plug and Play" platform approach that is well suited for use against a wide range of biological threats and amenable to rapid, large-scale production," said Rahul Basu, scientist at GeoVax and lead author on the study.

Vaccines produced in this platform are safe, highly immunogenic, and effective against a wide range of indications. The vaccines are suitable for repeated use, stable at refrigerator temperatures or lyophilized for non-cold chain needle-free application, and amenable to rapid and affordable scale-up for use in both epidemic response and routine vaccination.

"A significant unmet medical need exists for vaccine platform technologies to respond rapidly and effectively against biological threats," said Mr. Basu, "Preferably, such platforms should deliver vaccines that are safe and confer full protection after a single dose."

In proof-of-concept studies, the researchers tested three independent vaccines against three different families of viruses. Each vaccine demonstrated full protection after a single dose, using various lethal challenge models. For the Zika vaccine, a single inoculation of MVA-Zika vaccine in normal (immunocompetent) mice provided 100% protection against a lethal challenge dose of a neurovirulent ZIKV delivered directly into the brain. A single inoculation of MVA-VLP-Ebola vaccine candidate provided full protection in a rhesus monkey lethal challenge model. A single inoculation of MVA-VLP-LASV vaccine protected mice against a lethal challenge delivered directly into the brain.

"To demonstrate a broad utility of the platform, we developed prophylactic and therapeutic vaccines for other infectious diseases as well as cancer," said Mr. Basu. These included prophylactic and therapeutic vaccines for HIV (already in advanced clinical trials), preventive vaccines for Marburg, Sudan and Malaria, all with major epidemic potential with high human lethality, as well as therapeutic vaccines for chronic hepatitis B infections and tumor-associated antigen (TAA)-based-cancer vaccines.

These studies on single-dose vaccines for emerging infectious diseases were supported with funding from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) and performed at laboratories of the Centers for Disease Control, (CDC) in Fort Collins, CO, Institute of Human Virology, University of MD and NIH's Rocky Mountain Laboratories have demonstrated the broad utility of the platform. These are described in a Late-breaking presentation at the ASM Microbe 2018 meeting in Atlanta.

What we eat has important implications for our health--and for what we spend on healthcare. New research suggests improving the quality of the average American's diet could substantially reduce costs associated with heart disease, diabetes, cancer and other major health problems.

The study is the first to comprehensively analyze the potential cost implications of improved adherence to healthy dietary patterns (as measured by the Healthy Eating Index (HEI) and the Mediterranean-style diet (MED) score) among US adults across major chronic disease types. Previous research has focused on specific populations or specific conditions, such as heart disease.

"We found that increasing adherence to healthy dietary patterns by even 20 percent at a population level has the potential to save more than $20 billion in both direct and indirect costs associated with 10 major health outcomes," said lead study author Dr. Carolyn Scrafford, senior managing scientist at Exponent, a scientific consulting firm. "That's a significant saving from what we believe is a realistic shift in diet quality."

Scrafford will present the research at the American Society for Nutrition annual meeting during Nutrition 2018, held June 9-12, 2018 in Boston. The research project was funded by the National Dairy Council.

Scrafford's team estimated cost savings under two scenarios. The more conservative scenario looks at the savings that could be realized if US adults increased their adherence to a healthy dietary pattern by 20 percent, as measured by two metrics of diet quality: the Healthy Eating Index (HEI) and the Mediterranean-style diet (MED) score. The more ambitious scenario projects savings that could result if US adults achieved an 80 percent score on those same metrics.

Both the HEI and the MED are markers of what are considered healthy dietary patterns. The HEI is used frequently in the US to evaluate a US-style diet and reflects adherence with the 2015-2020 Dietary Guidelines for Americans while the MED was first used to describe the diet of countries in the Mediterranean region and emphasizes components such as fish, nuts, and fruits, along with olive oil as a healthy fat source.

The average US adult currently shows about 60 percent adherence to the HEI. If this were increased to 72 percent adherence (a relative increase of 20 percent), the analysis shows the US could save $30-47 billion in health-related costs annually. Under the more ambitious scenario, if the average US adult increased their adherence to 80 percent of the HEI, the researchers project an annual savings of $52-82 billion.

Close to half of these savings result from a reduction in costs associated with heart disease alone, with additional savings from reductions in costs associated with cancer and type 2 diabetes. Because heart disease in the US is so prevalent, so costly and so heavily influenced by diet, a small improvement in diet quality can result in meaningful cost savings, researchers say.

The average US adult currently scores a 3.5 out of 9 possible points on the MED score used to assess adherence to the Mediterranean-style diet. If this adherence were raised by 20 percent, the researchers project an annual savings of about $21-26 billion. The lower estimate includes only breast, colorectal and prostate cancer along with five other health outcomes (coronary heart disease, stroke, type 2 diabetes, hip fractures and Alzheimer's disease) while the higher estimate includes savings related to all cancer types along with the same five other health outcomes. Annual savings could reach $112-135 billion if Americans increased their MED adherence to 80 percent by incorporating more components of the Mediterranean-style diet.

"Our results suggest that it's worthwhile to educate Americans on these dietary patterns and their components, to encourage them to make little changes to improve their diet quality," said Scrafford.

To estimate how the healthy US- and Mediterranean-style dietary patterns influence rates of disease among adults in the US, the researchers systematically analyzed the published scientific literature to identify recent meta-analyses assessing observed associations between specific chronic health outcomes and adherence as measured by the HEI or MED scores. They then used the data in those studies to model the expected increase or decrease in risk of the health outcomes among healthy US adults under modeled levels of adherence to these healthy dietary patterns.

To estimate healthcare costs, the team used data from the American Heart Association, American Diabetes Association and National Cancer Institute of the National Institutes of Health, along with case reports tracking costs associated with hip fractures and Alzheimer's disease. Cost estimates included both direct costs--such as medical fees, devices and drugs--and indirect costs, such as lost wages and caregiver burden, where available.

While the research models hypothetical scenarios of increased adherence to healthy dietary patterns and it is unlikely that Americans could change their dietary patterns overnight or that the projected health improvements would immediately reduce health-related costs, the numbers provide a reference point for understanding the potential benefits of adopting a healthier diet, Scrafford said. The research was driven by the increasing understanding of the importance of overall dietary patterns rather than individual nutrients or foods.

Carolyn Scrafford will present this research on Sunday, June 10, from 8 a.m.-6 p.m. in the Hynes Convention Center, Exhibit Hall D (poster 811) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

Please note that abstracts presented at Nutrition 2018 were evaluated and selected by a committee of experts but have not generally undergone the same peer review process required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available.

June 9, 2018 - Atlanta, GA - Researchers from the Emory Antibiotic Resistance Center describe the first strain of carbapenem-resistant, hypermucoviscous Klebsiella pneumoniae exhibiting colistin heteroresistance and enhanced virulence isolated from a patient in the United States. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology, held from June 7th to 11th, in Atlanta, Georgia.

"The problem of antibiotic resistance is becoming increasingly alarming. The combination of increased virulence and multidrug resistance makes the situation worse," said Dr. David Weiss, director of the Emory Antibiotic Resistance Center.

The researchers showed that the K. pneumoniae isolate was heteroresistant to the last resort antibiotic colistin. This means that a small subpopulation of cells showed resistance. Heteroresistance is more difficult to detect with standard antibiotic susceptibility tests in clinical microbiology labs, and this isolate was classified as susceptible to colistin by standard methods. This discrepancy is particularly important, as Weiss' lab has shown that such undetected colistin heteroresistance can cause antibiotic treatment failure in mice.

In a hospital in Hangzhou, China, a 2016 deadly outbreak of carbapenem-resistant, hypervirulent K. pneumoniae was recently reported in Lancet Infectious Diseases.

"The isolate we are studying is not nearly as virulent (able to cause disease) in a mouse model as the bacteria from China," said Dr. Weiss, "However, finding the combination of antibiotic resistance and enhanced virulence from a clinical isolate in the United States (New York) is still alarming." The previously reported hypervirulent forms were largely antibiotic susceptible. Carbapenem-resistant K. pneumoniae, part of the carbapenem-resistant enterobacteriaceae (CRE) superbug family, is considered an urgent (top 3) threat by the CDC.

The researchers are urging more monitoring for this form of bacteria, which have the potential for increased virulence and may be especially worrisome in healthcare settings.

Jessie Wozniak, a Microbiology and Molecular Genetics graduate student at Emory University School of Medicine, and her colleagues examined 265 isolates of carbapenem-resistant K. pneumoniae from the Emerging Infections Program's Multi-site Gram-negative Surveillance Initiative, using a simple "string test."

"The string test is very low-tech," Wozniak says. "You take a loop, touch it to the bacterial colony, and pull back. The hypermucoviscous one looks like a string of cheese being pulled from a pizza."

The stretchiness observed by the string test is a sign that the bacteria produce more capsule polysaccharide, and has been associated with enhanced virulence previously. Wozniak verified that the isolate was approximately ten times more virulent in mice than other isolates of the same sequence type.

She also used whole-genome sequencing to discover that the U.S. isolate carried several antibiotic resistance genes, along with a new arrangement of virulence genes, but not the same set seen in similar K. pneumoniae isolates from Asian countries.

June 9, 2018 - Atlanta, GA - Results from a pivotal trial of PRO 140, a new HIV therapy, show that PRO 140 is an effective, long-acting therapeutic in combination with antiretroviral treatment (ART) for previously treated HIV-1 infected patients. This is an ongoing randomized, double-blind, placebo-controlled trial. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology, held from June 7th to June 11th in Atlanta, GA.

PRO 140 is a novel humanized CCR5 monoclonal antibody under development by CytoDyn Inc. (OTC.QB: CYDY). At one week following a single subcutaneous injection of PRO 140 together with existing ART, patients achieved a mean viral load reduction of approximately 97% from a mean baseline viral load. The trial met its primary efficacy endpoint: the proportion of patients with ?0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the one-week treatment period (p?0.01).

"While ART has greatly advanced over the years, new agents are needed to improve the potency and pharmacokinetic profiles, decrease toxicity, combat drug resistance, and improve convenience to facilitate patient compliance," said Nader Pourhassan, Ph.D., CytoDyn's President and Chief Executive Officer. "These trial results support the continued development of PRO 140 as a simple-to-administer, long-acting HIV-1 therapy that, together with optimized background ART, can provide a valuable new therapeutic option for patients who have become resistant to multi-antiretroviral agents."

Fifty patients with demonstrated evidence of HIV-1 replication on existing ART and documented resistance to two or more antiretroviral drug classes participated in the ongoing two-part pivotal trial. In the first one-week portion of the trial, patients were randomized into two arms with both arms continuing on existing ART. The researchers administered a single PRO 140 350 mg subcutaneous injection to one arm of the trial, and the second arm received a placebo.

The trial met the primary efficacy endpoint: the proportion of patients with ?0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the one-week treatment period (p ~ 0.0032). In part two of the trial, all patients received 24-weeks of PRO 140 subcutaneous with optimized background ART in an open-label setting. Continuing access to PRO 140 is provided to patients completing 25 weeks in the trial.

"With the highly favorable efficacy results for this combination therapy trial, and data from our previous trials and our ongoing monotherapy trial, we are now working toward the filing of a Biological License Application, or BLA, with the FDA for PRO 140 in the combination therapy indication," added Dr. Pourhassan.

Primary efficacy results of the trial are being presented on June 9 from 11:00 am-1:00 pm ET in a Late-Breaker Abstract session at ASM Microbe 2018 in the Exhibit and Poster Hall, Building B, Halls B2-B5, Georgia World Congress Center in Atlanta. The CytoDyn-sponsored trial is being presented by Kush Dhody of Amarex Clinical Research, LLC. Additional authors include Kazem Kazempour, Ph.D. of Amarex Clinical Research, LLC, Nader Pourhassan of CytoDyn Inc., and Paul Maddon, M.D., Ph.D., PRO 140 discoverer.

The climate throughout Mars' early history has long been debated - was the Red Planet warm and wet, or cold and icy? New research published in Icarus provides evidence for the latter.

Mars is littered with valley networks, deltas and lake deposits, meaning it must have had freely flowing water at some point, probably around 4 billion years ago. But climate models of the planet's deep past haven't been able to produce warm enough conditions to allow liquid water on the surface.

"There are people trying to model Mars' ancient climate using the same kind of models we use here on Earth, and they're having a really hard time doing it. It's difficult to create a warm ancient Mars because the sun was a lot fainter then. The whole solar system was cooler," said Briony Horgan, an assistant professor of earth, atmospheric and planetary sciences at Purdue University. "While a lot of people are using climate models, we're coming at this from a unique perspective - what does the volcanic record of Mars tell us?"

Volcanism was abundant throughout Mars' early history. There are large, broad volcanoes on some of the planet's widely studied regions, but less is known about a region of low and smooth topography in the southern highlands known as Sisyphi Planum. Here, there are more than 100 flat-topped mounds known as the Sisyphi Montes, which could be volcanic in origin.

When volcanoes erupt beneath ice sheets and glaciers on Earth, the combination of heat and melt water create flat-topped, steep-sided mountains called "tuyas," or table mountains. When subglacial eruptions don't breach the surface of the ice, the tops of the volcanoes remain cone-shaped instead of becoming flat. The minerology produced during these events is unique due to the interaction between hot lava and cold glacial meltwater.

Sheridan Ackiss, a Ph.D. candidate at Purdue and lead author of the paper, used images from NASA's Compact Reconnaissance Imaging Spectrometers for Mars (CRISM) to find out if the mineral makeup of the region was consistent with subglacial volcanism.

CRISM detects both the visible range and shorter wavelengths of light, which helps the instrument's operators identify a broad range of minerals on the Martian surface. At visible wavelengths, the way light is reflected is strongly influenced by iron, whereas at infrared wavelengths, CRISM can pick up features from carbonate, sulfate, hydroxyl and water incorporated in mineral crystals.

"Each rock has a specific fingerprint, and you can identify that with reflections of light," Ackiss said.

The findings identify three distinct mineral combinations in the region, dominated by gypsum, polyhydrated sulfates and a smectite-zeolite-iron oxide mixture - all of which have been associated with volcanoes in glacial environments.

"We now have two sets of data, minerals and morphology, that say there had to have been ice on Mars at some point in time," said Ackiss. "And it was probably relatively late in Mars' history."

Ackiss' team hopes their findings can be used as a reference point for other regions on Mars with a volcanic history. If researchers could find evidence for volcanic activity under ice sheets elsewhere, it would solidify the case for a very cold ancient Mars. But fear not, space enthusiasts, this doesn't eliminate the possibility of past life on Mars.

"Even if Mars was a cold and icy wasteland, these volcanic eruptions interacting with ice sheets could have created a little happy place for microbes to exist," Horgan said. "This is the kind of place you'd want to go to understand how life would've survived on Mars during that time."