Culture

Researchers at Griffith University working with Australia's Commonwealth Scientific and Industrial Research Organisation (CSIRO) have unveiled a stunningly accurate technique for scientific measurements which uses a single atom as the sensor, with sensitivity down to 100 zeptoNewtons.

Using highly miniaturised segmented-style Fresnel lenses - the same design used in lighthouses for more than a century - which enable exceptionally high-quality images of a single atom, the scientists have been able to detect position displacements with nanometre precision in three dimensions.

"Our atom is missing one electron, so it's very sensitive to electrical fields. By measuring the displacement, we've built a very sensitive tool for measuring electrical forces." Dr Erik Streed, of the Centre for Quantum Dynamics, explained.

"100 zeptoNewtons is a very small force. That's about the same as the force of gravity between a person in Brisbane and a person in Canberra. It can be used to investigate what's occurring on surfaces, which will help miniaturise ion trap type quantum computers and other quantum devices."

Griffith researchers have been pioneering the application of such lenses in quantum physics since 2011, but this is the first time they have been used to achieve such high levels of accuracy in sensing the forces influencing a particular atom.

By intentionally moving their optics slightly out of focus, the researchers were able to measure displacements in all three dimensions, with the third direction determined by if the atom was shifting back into focus or further out of focus.

Along with the research's applications for fundamental physics of magnetic, atomic, quantum and surface phenomena, Dr Streed is also working as part of Griffith's Institute for Glycomics to adapt these sorts of quantum technologies for medical and biological research.

"With the Institute for Glycomics I'm also interested in developing this into a tool to measure the electrical fields outside a single isolated biomolecule, like the dipole moment, as a new way to help understand how they behave," he said.

The heightened accuracy of the technique is precisely due to the use of a solo atom as a 'probe' in obtaining these measurements. Previous techniques similar to this used many atoms as the electric force sensor and were limited to only one dimension.

Alexandria, VA, USA - At the 47th Annual Meeting of the American Association for Dental Research (AADR), held in conjunction with the 42nd Annual Meeting of the Canadian Association for Dental Research (CADR), Prescott McWilliams, United States Air Force, San Antonio, Texas and the Uniformed Services University of the Health Sciences (USU), Postgraduate Dental College (PDC), presented a poster titled "Effect of Deployment on Use of E-Cigarettes in U.S. Military." The AADR/CADR Annual Meeting is in Fort Lauderdale, Fla., USA from March 21-24, 2018.

Little research has examined a potential association between military deployment and e-cigarette use. "Our objective was to develop an understanding of how military deployment affects the e-cigarette habit and its associated behaviors among a sample of Army and Air Force service members," said McWilliams.

Information on the prevalence, perception and use of e-cigarettes, in addition to history of deployment, was obtained using data from the "Tobacco Use Among Service Members" survey sponsored by the Murtha Cancer Center and the Air Force Postgraduate Dental School within the USU PDC.

In the study population of 2,500 participants, 45% had deployed, 14% had used e-cigarettes, with 5.7% experiencing both. Most users (67%) considered e-cigarettes to be less harmful than traditional cigarettes.

In multivariable logistic regression analysis, being deployed to a combat unit was associated with lower odds of using e-cigarettes. Stratified analyses by perception of harm showed that soldiers deployed to combat units who perceived e-cigarettes to be less harmful than traditional cigarettes had a 61% reduction in risk of using E-cigarettes.

McWilliams reported that being deployed to a combat unit was associated with lower odds of e-cigarette use, particularly among those with less perceived harm. These results demonstrate the need for better understanding the health effects associated with e-cigarettes and the development of targeted cessation/educational campaigns. Future research may include an analysis to identify factors associated with decreased e-cigarette use among those deployed to combat units.

Alexandria, VA, USA - At the 47th Annual Meeting of the American Association for Dental Research (AADR), held in conjunction with the 42nd Annual Meeting of the Canadian Association for Dental Research (CADR), Veerasathpurush Allareddy, University of Iowa, College of Dentistry & Dental Clinics, Iowa City, presented a poster titled "Opioid Abuse/Dependence in Those Hospitalized Due to Periapical Abscess." The AADR/CADR Annual Meeting is in Fort Lauderdale, Fla., USA from March 21-24, 2018.

Opioid abuse/dependence (OAD) is an emerging public health crisis in the USA. The objective of this study was to estimate the nationwide prevalence of OAD in those hospitalized due to periapical abscess in the U.S., testing the hypothesis that a mix of patient and geography related factors are associated with OAD in this cohort.

Using the Nationwide Inpatient Sample for years 2012 to 2014, all patients that were hospitalized due to periapical abscess were selected for analysis. OAD was identified and used as the outcome variable, and a mix of patient and geographic factors were used as independent variables.

During the study period 30,040 patients were hospitalized due to periapical abscess -- 1.5% of these had OAD. Those aged 18 to 29 years were associated with higher odds for OAD compared to those aged 45 to 64 years. Blacks were associated with lower odds for OAD compared to Whites and those covered by Medicare, Medicaid and Uninsured were associated with higher odds for OAD compared to those covered by private insurance.

Odds of OAD increased with co-morbid burden but there were no significant variations in OAD across geographic regions of USA and by hospital location/teaching status. Household income levels and gender were also not significantly associated with OAD.

"From this study," said Veerasathpurush Allareddy, "we see that the high risk groups that are likely to have OAD were identified amongst those hospitalized due to periapical abscess."

The study findings are based on the Nationwide Inpatient Sample which is sponsored by the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality.

A new Drexel University study found that 30 percent of mayors don't believe civic policies can reduce health disparities in their cities, and it appears that individual political ideology is strongly related to those beliefs.

The study surveyed more than 500 mayors and health commissioners of cities across the United States, gauging their beliefs on health disparities in their own cities. A health disparity occurs when one group within a population has disproportionately worse health than another group. In the United States, the problem is widespread. The nation's poorest residents are more than three times as likely to be in bad health than the richest segment of the population.

Led by Jonathan Purtle, DrPH, assistant professor in the Dornsife School of Public Health, the study showed that only about 8 percent of mayors who identified as socially conservative believed municipal polices would have a major impact on health disparities in their city. Among socially moderate and liberal mayors, approximately 23 and 29 percent (respectively) believed city policies could have major influences.

"There are lots of things that mayors and health commissioners can do that could influence health disparities -- such as influencing pedestrian safety , decisions on the location and offerings of health clinics and programs, and decisions related to the education system," said Purtle, who published the findings in the American Journal of Public Health. "They can play a major role in determining which communities in a city get what, how much they get, and when they get it."

Purtle and his study team hoped this research would reveal some prime areas for making inroads with civic decision-makers.

"I think policymaking is where the great opportunities lie," said Jennifer Kolker, MPH, a co-author, associate clinical professor and associate dean for Public Health Practice in the Dornsife School of Public Health. "We can help mayors and health commissioners recognize the policy impact that they can have."

One area where political and ideological influences were found, surprisingly, was among people holding the position of health commissioner -- generally a less "political" job than mayor since they're appointed rather than elected

While roughly 45 percent of all health commissioners felt city policies could have a major impact on health disparities, just about 14 percent of socially conservative health commissioners agreed, compared to 39 percent of moderate and 55 percent of liberal commissioners.

"I was surprised," Purtle said. "The findings underscore, in my opinion, how difficult it is for people to separate their personal ideology from their professional roles."

"It's important for leaders to be aware of that difficulty in making day-to-day decisions," Kolker added.

Rosie Mae Henson, MPH, another co-author as well as an Urban Health Collaborative fellow and PhD student in the Dornsife School of Public Health, pointed out that more than 90 percent of those surveyed did recognize that there was some degree of health disparity in their city.

"Their belief that city policies might not have an impact could reflect differential views on the role of government or perceived or real barriers to implementing policies, like a lack of awareness of their policy options. There are efforts underway to try to change this," Henson said.

One such effort, she said, is the National League of Cities, which has an initiative designed to educate city leaders on what exactly they can do to promote health in their cities.

Public health researchers and advocates also should not be shy in communicating with decision-makers in cities, the study team feels.

Knowing about the ideological divide that might be coloring how some view their cities' health concerns and the policies that shape them is invaluable for effectively reaching out.

"Language really matters when it comes to framing messages because our ideological values can be so strong that we are primed to immediately accept or reject a message," Henson said.

"People in public health must craft better messages that are tailored to policymakers with different ideologies," Purtle said. "We need to meet people where they're at when communicating about complex issues like health disparities, and use words and frames that are clear and compelling to people with different leanings."

Tokyo, Japan - Researchers from Tokyo Metropolitan University studied the neural response of Japanese junior high school students learning English as a second language, while listening to English sentences. More proficient boys showed more activation in parts of the brain associated with grammatical rules (syntax); girls used a wider range of language information, including speech sounds (phonology) and meaning of words and sentences (semantics). These discoveries may help optimize how boys and girls are taught English.

Children learn their native language with enviable ease and speed, but learning a second language is a far more varied process; though there has been much research into how the brain deals with new languages, we still don't know how variations in gender, age etc. specifically affect how we learn a new tongue.

A team led by Prof. Fumitaka Homae studied a rarely targeted population for this subject: Japanese junior high school students learning English as a second language in a school environment. The majority of work into the neuroscience behind learning a second language is based on immigrant populations in the United States, and children in the multi-lingual environment of Europe.

The boys and girls were given a standardized English test and a test of "Working Memory", a temporary storage in the brain used to organize, manipulate and analyze newly arrived information. They then listened to English sentences, including some with grammatical errors; observations of brain activity were taken using functional near-infrared spectroscopy (fNIRS) and event-related potential (ERP) measurements. fNIRS tells us which parts of the brain are active; ERP gives us an idea of how brain activity varies with time.

The results revealed a surprising disparity in how boys and girls deal with sentences. The girls performed better on the tests, and had more working memory. However, boys showed no correlation between working memory and performance, while girls did. Looking at brain activity, fNIRS revealed that boys showed increased activation with proficiency in the front of the brain when they heard a correct sentence, while girls showed more at the back. The front is linked with "syntactic" processing i.e. rule-based understanding of sentences; the back is associated with a wider range of language processing. Interestingly, boys displayed an overall decreased response for incorrect sentences; girls showed the exact opposite.

ERPs also showed disparities, with boys exhibiting a strong response to incorrect sentences from an early time, a phase thought to be associated with "syntactic" processing. Girls only showed a difference between correct and incorrect sentences at later times.

The emerging picture is of two different strategies to cope with a second language. Boys leverage efficient processing and rule-based "implicit" thinking; girls draw on a wider range of linguistic information, achieving "explicit" comprehension of sentences. A cursory look at test scores may have simply pointed to girls being "better" at learning English, but the mechanisms tell a far more interesting story.

A clearer picture of how boys and girls learn a second language (in this case, English) has the potential to revolutionize teaching in schools, building methods and syllabi to address directly strengths and weaknesses for both boys and girls.

This work was supported by two MEXT Grants-in-Aid for Scientific Research on Innovative Areas, "Integrative Research toward Elucidation of Generative Brain Systems for Individuality" and "The Science of Personalized Value Development through Adolescence: Integration of Brain, Real-world, and Life-Course Approaches". This project is part of work carried out at the Language, Brain and Genetics Research Center in Tokyo Metropolitan University. The manuscript reporting this finding has been published online in Frontiers in Human Neuroscience.

Insights from past failures can help boost performance on a new task -- and a new study is the first to explain why. US researchers report that writing critically about past setbacks leads to lower levels of the "stress" hormone, cortisol, and more careful choices when faced with a new stressful task, resulting in improved performance. The study, published today in open access journal Frontiers in Behavioral Neuroscience, is the first demonstration that writing and thinking deeply about a past failure improves the body's response to stress and enhances performance on a new task. This technique may be useful in improving performance in many areas, including therapeutic settings, education and sports.

People are often advised to "stay positive" when faced with a challenging task. However, a vast body of research suggests that paying close attention to negative events or feelings -- by either meditating or writing about them -- can actually lead to positive outcomes.

But why does this counter-intuitive approach lead to benefits? To investigate this question, Brynne DiMenichi, a doctoral candidate from Rutgers University-Newark, together with other researchers from the University of Pennsylvania and Duke University, examined the effect of writing about past failures on future task performance in two groups of volunteers.

A test group wrote about their past failures while a control group wrote about a topic not related to themselves. The researchers used salivary cortisol levels to provide a physiological readout of the stress experienced by the people in both groups. These levels were comparable across the test and control groups at the start of the study.

DiMenichi and colleagues then measured the performance of the volunteers on a new stressful task and continued to monitor their cortisol levels. They found that the test group had lower cortisol levels compared to the control group when performing the new challenge.

"We didn't find that writing itself had a direct relationship on the body's stress responses," says DiMenichi. "Instead, our results suggest that, in a future stressful situation, having previously written about a past failure causes the body's stress response to look more similar to someone who isn't exposed to stress at all."

The researchers also found that volunteers who wrote about a past failure made more careful choices on a new task, and overall performed better than the control group.

"Together, these findings indicate that writing and thinking critically about a past failure can prepare an individual both physiologically and cognitively for new challenges," observes DiMenichi.

While everyone experiences setbacks and stress at some point in their lives, this study may provide insight about how one can use these experiences to better perform in future challenges.

"It provides anyone who wants to utilize this technique in an educational, sports, or even therapeutic setting with clear-cut evidence of expressive writing's effectiveness," says DiMenichi. "However, it is difficult to compare laboratory measures of cognitive performance to performance on say, the Olympic track. Future research can examine the effect of writing manipulation on actual athletic performance."

The article is part of a special research collection on the impact of stress on cognition and motivation.

Alexandria, VA, USA - At the 47th Annual Meeting of the American Association for Dental Research (AADR), held in conjunction with the 42nd Annual Meeting of the Canadian Association for Dental Research (CADR), Hyun Hong, The Dental College of Georgia at Augusta University, presented a poster titled "Investigating the Enigmatic Link Between Periodontal Inflammation and Retinal Degeneration." The AADR/CADR Annual Meeting is in Fort Lauderdale, Fla., USA from March 21-24, 2018.

Many clinical studies link Chronic Periodontitis (CP) to various systemic disorders and lately age-related macular degeneration (AMD), a leading cause of irreversible vision loss in elderly, is found to be associated with periodontal disease. The keystone oral-pathobiont and one of the major causative organism for CP, Porphyromonas gingivalis (Pg), has been identified with the ability to invade epithelial, fibroblasts and dendritic cells. "Our study was designed with an objective to interrogate the role of Pg and its fimbriae-mediated infection of human retinal-pigment epithelial cells and retro-orbitally injected mice retina, thus revealing possible molecular links between CP and AMD," said Hyun Hong (Predoctoral dental student, Summer Research Program, Dental College of Georgia) and Dr. Pachiappan Arjunan, the Principal Investigator, who directed this study (Assistant Professor, Department of Periodontics, Dental College of Georgia, Augusta University).

Human retinal-pigment epithelial cells were infected with Pg and its isogenic mutant strains and genes were analyzed by qPCR.

The results showed that human retinal-pigment epithelial cells take up Pg381 and that qPCR shows a significant increase in expression levels of genes, important in immunosuppression and angiogenesis/neo-vascularization markers compared with uninfected control.

Certain complement regulatory-related genes were upregulated, while others were downregulated. In a mouse model, AMD-related effects on mouse retinae were induced by Pg-injection compared to control group.

Dr. Arjunan states that, "This is the first study to demonstrate the link between oral pathobiont infection and AMD pathogenesis and that Pg can invade human retinal-pigment epithelial cells & elevate AMD-related genes which might be the target molecules for both diseases".

Further, successive ongoing studies in Dr. Arjunan's laboratory in collaboration with Dr. Christopher W Cutler (Professor and Chair, Department of Periodontics, Dental collage of Georgia, Augusta University), could distinguish specific causal role of Pg in AMD pathogenesis. The first part of this work will be published very soon, he added.

This work was funded by the Department of Periodontics, Dental College of Georgia, Augusta University and seeks additional funding support from National Institutes of Health (NIH) to accomplish the objective of this innovative study.

WASHINGTON, DC AND SILVER SPRING, MD (March 23, 2018)--Despite the high prevalence of obesity among U.S. adults, provision of recommended treatments for obesity remains low. Providers cite lack of time, lack of reimbursement, and lack of knowledge as major barriers to treating patients with obesity. A new study published in Obesity assessed health care professionals' (HCPs') knowledge of evidence-based guidelines for nonsurgical treatment of obesity.

In this study, the authors conducted a web-based survey of a nationally representative sample of 1506 internists, family practitioners, obstetricians/gynecologists, and nurse practitioners to determine their understanding of obesity treatment guidelines. The results indicate that most providers lack knowledge and understanding of recommended obesity treatments, such as behavioral counseling and pharmacotherapy.

Author William Dietz, MD, PhD, FTOS, Past President of The Obesity Society, Director of the STOP Obesity Alliance and Chair of the Sumner M. Redstone Global Center for Prevention and Wellness at the Milken Institute School of Public Health at The George Washington University, said, "Our findings offer health professionals and medical educators a strong rationale for incorporating enhanced training on the prevention and management of obesity into their curricula."

The Obesity Society Spokesperson Ken Fujioka, MD, FTOS, Director of the Center for Weight Management and Director of the Nutrition and Metabolic Research Center at Scripps Clinic, said, "This is a big-time paper that clearly demonstrates the lack of basic knowledge about obesity in the health care community. Admittedly, we have always known this, but this is clear evidence that we have a major problem because obesity is the most common disease seen in primary care." These findings strongly suggest that additional obesity training is needed.

Additionally, in an accompanying editorial published in Obesity, Robert Kushner, MD, FTOS, examines the impact of this study. "The study suggests that more obesity education is needed among primary health care providers that focuses on knowledge along with enhanced competencies in patient care management, communication, and behavior change," said Dr. Kushner, Past President of The Obesity Society, Professor of Medicine at Northwestern University Feinberg School of Medicine, and Director of the Center for Lifestyle Medicine at Northwestern Medicine in Chicago, IL. Overall, more obesity education and training are needed among health care professionals.

Neurology researchers investigating a rare but devastating neurological regression in infants have discovered the cause: gene mutations that severely disrupt crucial functions in mitochondria, the energy-producing structures within cells. The specific disease mechanism, in which mutations disrupt a critical mitochondrial enzyme, has not previously been implicated in a human disease.

"We uncovered the cause of this mysterious neurodegenerative disease, and now we understand better what happens in the brains of these children," said lead investigator Ingo Helbig, MD, a pediatric neurologist at Children's Hospital of Philadelphia (CHOP). "This new understanding is the very first step toward potentially finding a treatment."

Helbig collaborated with researchers from Germany, Australia and the U.S. in this study, published online today in the American Journal of Human Genetics. The other two co-senior authors were Dr. Franz-Josef Mueller, of the University Hospital Schleswig Holstein, Kiel, Germany; and Dr. Johan L.K. Van Hove, of the University of Colorado.

For Helbig, now an attending physician in the Neurogenetics Program at CHOP and a specialist in genetic epilepsies, the finding builds on an experience early in his medical training when he was involved in the care of an infant girl with severe epilepsy. The child suffered sudden neurological regression after a fever, for no apparent reason. Imaging studies showed the child lost brain volume, mainly in the cerebellum.

The symptoms appeared to mimic those of a progressive neurological disease. Instead, it turned out to be due to energy failure, based in malfunctioning mitochondria, but this became apparent only after nearly a decade of research.

The current study reports on five affected children in four families, including the original patient and her sibling. Both siblings, along with a third patient in the study, died before six years of age. None of the five children were able to walk or speak, and all but one had seizures.

The research team used whole-exome sequencing to pinpoint the causative mutations in the gene PMPCB. Because that gene is highly conserved across yeast and humans, the researchers conducted experiments in a common yeast to investigate the effects of the mutation

The researchers found that mutations in PMPCB interfered with the function of the enzyme mitochondrial processing protease (MPP), which transports proteins into mitochondria to be cut up as part of normal biological processing. Disrupting that process, in turn, blocked the production of iron-sulfur clusters that are crucial to energy metabolism and other cellular functions.

In infants, the diminished activity of MPP causes a deficiency of biological energy. An infection or fever triggers a crisis--a cascade of severe events, including brain atrophy and the neurological regression seen in the patients. The symptoms appear similar to those seen in the well-known mitochondrial disorder Leigh's syndrome.

The biological pathways that MPP is involved in are closely related to the more common neurological disease Friedreich's ataxia, which is also actively studied by researchers at CHOP. In fact, frataxin, the protein altered in Friedreich's ataxia, is one of the main targets of MPP. The conditions however, are very different, and the PMPCB-related disorders identified by Helbig and his collaborators are more severe than Friedreich's ataxia.

The current findings, said Helbig, set the stage for follow-up research in biological implications, for instance, by further investigation in yeast models of the disease. "If we better understand biological pathways and mechanisms," he added, "we may be able to start screening for compounds that may suggest potential treatments for this condition."

See Helbig's research blog, "Beyond the Ion Channel" for his description of the discovery of PMPCB's role in this condition.

The population of bacteria in the pancreas increases more than a thousand fold in patients with pancreatic cancer, and becomes dominated by species that prevent the immune system from attacking tumor cells.

These are the findings of a study conducted in mice and in patients with pancreatic ductal adenocarcinoma (PDA), a form of cancer that is usually fatal within two years. Led by researchers at NYU School of Medicine, Perlmutter Cancer Center, and NYU College of Dentistry, the study published online March 22 in Cancer Discovery, a journal of the American Association for Cancer Research.

Specifically, the study found that removing bacteria from the gut and pancreas by treating mice with antibiotics slowed cancer growth and reprogrammed immune cells to again "take notice" of cancer cells. Oral antibiotics also increased roughly threefold the efficacy of checkpoint inhibitors, a form of immunotherapy that had previously failed in pancreatic cancer clinical trials, to bring about a strong anti-tumor shift in immunity.

Experiments found that in patients with PDA, pathogenic gut bacteria migrate to the pancreas through the pancreatic duct, a tube that normally drains digestive juices from the pancreas into the intestines. Once in the pancreas, this abnormal bacterial mix (microbiome) gives off cellular components that shut down the immune system to promote cancer growth, say the authors.

"While combinations of changes in genes like KRAS cause cells to grow abnormally and form pancreatic tumors, our study shows that bacteria change the immune environment around cancer cells to let them grow faster in some patients than others, despite their having the same genetics," says senior study co-author George Miller, MD, co-leader of the Tumor Immunology Research Program at Perlmutter, the H. Leon Pachter, MD, Professor in the Department of Surgery, and professor of Cell Biology at NYU Langone Health.

"Our results have implications for understanding immune-suppression in pancreatic cancer and its reversal in the clinic," says senior co-author Deepak Saxena, PhD, associate professor of Basic Science and Craniofacial Biology at NYU College of Dentistry. "Studies already underway in our labs seek to confirm the bacterial species most able to shut down the immune reaction to cancer cells, setting the stage for new bacteria-based diagnostic tests, combinations of antibiotics and immunotherapies, and perhaps for probiotics that prevent cancer in high-risk patients."

On the one hand, the research team theorizes that changes in the genes that cause abnormal cell growth in the pancreas might also change the immune response in ways that favor the growth of different bacterial species than are found in normal individuals.

Alternatively, environmental factors like diet, other diseases, or common medications might cause bacterial changes in the gut that are reflected in the pancreatic microbiome.

Whatever the cause, the new study found that bacteria that are more abundant in pancreatic cancers - including groups of species called proteobacteria, actinobacteria, and fusobacteria - release cell membrane components (e.g. lipopolysaccharides) and proteins (e.g. flagellins) that shift macrophages, the key immune cells in the pancreas, into immune suppression.

Experiments showed that eliminating bacteria using antibiotics restored the ability of immune cells to recognize cancer cells, slowed pancreatic tumor growth, and reduced the number of cancer cells present (tumor burden) by 50 percent in study mice.

The researchers found that "bad" bacteria in pancreas tumors trigger immune cell "checkpoints" - sensors on immune cells that turn them off when they receive the right signal. These checkpoints normally function to prevent the immune system from attacking the body's own cells, but cancer cells hijack checkpoints to turn off immune responses that would otherwise destroy them. Checkpoint inhibitors are therapeutic antibodies that shut down checkpoint proteins to make tumors "visible" again to the immune system.

"Adding antibiotics improved the performance of a checkpoint inhibitor in a mouse model of PDA, as shown by an increase in T cells that could attack the tumors," says first co-author Mautin Hundeyin, MD, a postdoctoral fellow in Miller's lab. "Our study confirmed that, similar to what has been observed in patients with pancreatic cancer, checkpoint inhibition alone did not protect mice. This may be because, in the immunosuppressive environment of the tumor, there are too few immune cells around to be activated."

As a next step, the research team plans to soon begin recruiting patients into a clinical trial at Perlmutter Cancer Center to test whether a combination of antibiotics (ciprofloxacin and metronidazole) can improve the effectiveness of a checkpoint inhibitor (an anti-programmed death receptor 1 (PD-1) antibody) in PDA patients.

Cervical fluid samples gathered during routine Papanicolaou (Pap) tests are the basis of a new screening test for endometrial and ovarian cancers developed by researchers at the Johns Hopkins Kimmel Cancer Center.

PapSEEK detects mutations in DNA that have been identified for specific cancers sooner. Earlier detection of cancer could lead to earlier treatment and potentially better outcomes for patients.

The test uses cervical fluid samples to look for mutations in 18 genes, which are highly or commonly mutated in endometrial or ovarian cancers, and aneuploidy, the presence of abnormal numbers of chromosomes in cells. The researchers said their results showed the potential for mutation-based diagnostics to detect endometrial and ovarian cancers earlier.

Their findings were published in the March 21 issue of Science Translational Medicine.

"More than 86,000 U.S. cases of endometrial and ovarian cancer were diagnosed in 2017. Treatment often involves surgery and, in some cases, chemotherapy or radiation," said Amanda Nickles Fader, M.D., director of the Johns Hopkins Kelly Gynecological Oncology Service, Department of Gynecology and Obstetrics, and a corresponding author on this study.

"Additionally for young women who are diagnosed, loss of fertility is common. If we could detect the cancer earlier using a test like PapSEEK, the potential to achieve more cures and preserve fertility in select women could be realized."

Most cancers are curable if they are detected early, and the researchers are exploring ways to use cancer gene discoveries to develop cancer screening tests to improve cancer survival. They announced the development of CancerSEEK, a single blood test that screens for eight cancer types, and UroSEEK, a test that uses urine to detect for bladder and upper tract urothelial cancer.

PapSEEK targets the most common and most lethal gynecological cancers, endometrial and ovarian cancer. There is currently no screening test for endometrial cancer and, due to the obesity epidemic, it is on the rise, particularly in younger women.

"Gynecological cancers are responsible for approximately 25,000 deaths per year and are the third leading cause of cancer-related mortality," said Nickolas Papadopoulos, Ph.D., a senior author and an investigator at the Ludwig Center at Johns Hopkins. "Most of the deaths are caused by tumors that metastasize prior to the onset of symptoms. With PapSEEK, we are aiming to detect these cancers early when they are most curable."

Since fluid from the Pap test occasionally contains cells from the endometrium or ovaries, researchers found they could detect cancer cells from these organs that are present in the fluid.

The researchers studied 1,958 samples obtained from 1,658 women, including 658 endometrial or ovarian cancer patients and 1,002 healthy controls. Some participants provided two samples. Pap brush samples were obtained from 382 endometrial cancer patients and 245 ovarian cancer patients. PapSEEK was nearly 99 percent specific for cancer, and it detected 81 percent of endometrial cancers (78 percent were early-stage cancers) and 33 percent of ovarian cancers (34 percent were early-stage cancers).

Obtaining cervical fluid samples using a Tao brush, which extends further into the cervical canal and collects cells closer to where the cancers could originate, improved the sensitivity of the test. Testing plasma samples with Pap brush samples also increased the test's sensitivity.

Lucy Gilbert, M.D. MSc FRCOG, director of gynecologic oncology at McGill University Health Centre, said, "This allows sampling closer to where the cancers originated. Intrauterine sampling proved particularly important for increasing the detection of ovarian cancer."

Of the 123 endometrial cancer patients studied using Tao brush samples, PapSEEK identified cancer 93 percent of the time. Of the 51 ovarian cancer patients studied, 45 percent tested positive for cancer with PapSEEK. There were no false-positive results.

The Tao brush is not commonly used in the United States but is approved by the U.S. Food and Drug Administration for endometrial sampling. When the plasma and Pap brush samples were both tested, the sensitivity of the test for ovarian cancer increased to 63 percent.

More than 63,000 women are diagnosed with endometrial cancer in the U.S. each year, and more than 11,000 die each year from the disease. Ovarian cancer is less common but more lethal, affecting more than 22,000 women and killing about 14,000 in the U.S. each year.

"Diagnostic tests do not always reliably distinguish benign conditions from cancer, leading to unnecessary procedures," said Nickles Fader. "The high mortality associated with some gynecologic cancers makes screening a priority, and new diagnostic approaches are urgently needed."

"Our study demonstrates the ability to detect endometrial and ovarian cancer using cervical fluids obtained using two different methods," said Yuxuan Wang, first author on the study.

CAMBRIDGE, Mass, -- It seems like getting something for nothing, but you really can get drinkable water right out of the driest of desert air.

Even in the most arid places on Earth, there is some moisture in the air, and a practical way to extract that moisture could be a key to survival in such bone-dry locations. Now, researchers at MIT have proved that such an extraction system can work.

The new device, based on a concept the team first proposed last year, has now been field-tested in the very dry air of Tempe, Arizona, confirming the potential of the new method, though much work remains to scale up the process, the researchers say.

The new work is reported today in the journal Nature Communications and includes some significant improvements over the initial concept that was described last year in a paper in Science, says Evelyn Wang, the Gail E. Kendall Professor in the Department of Mechanical Engineering, who was the senior author of both papers. MIT postdoc Sameer Rao and former graduate student Hyunho Kim SM '14, PhD '18 were the lead authors of the latest paper, along with four others at MIT and the University of California at Berkeley.

Last year's paper drew a great deal of attention, Wang says. "It got a lot of hype, and some criticism," she says. Now, "all of the questions that were raised from last time were explicitly demonstrated in this paper. We've validated those points."

The system, based on relatively new high-surface-area materials called metal-organic frameworks (MOFs), can extract potable water from even the driest of desert air, the researchers say, with relative humidities as low as 10 percent. Current methods for extracting water from air require much higher levels - 100 percent humidity for fog-harvesting methods, and above 50 percent for dew-harvesting refrigeration-based systems, which also require large amounts of energy for cooling. So the new system could potentially fill an unmet need for water even in the world's driest regions.

By running a test device on a rooftop at Arizona State University in Tempe, Wang says, the team "was field-testing in a place that's representative of these arid areas, and showed that we can actually harvest the water, even in subzero dewpoints."

The test device was powered solely by sunlight, and although it was a small proof-of-concept device, if scaled up its output would be equivalent to more than a quarter-liter of water per day per kilogram of MOF, the researchers say. With an optimal material choice, output can be as high as three times that of the current version, says Kim. Unlike any of the existing methods for extracting water from air at very low humidities, "with this approach, you actually can do it, even under these extreme conditions," Wang says.

Not only does this system work at lower humidities than dew harvesting does, says Rao, but those systems require pumps and compressors that can wear out, whereas "this has no moving parts. It can be operated in a completely passive manner, in places with low humidity but large amounts of sunlight."

Whereas the team had previously described the possibility of running the system passively, Rao says, "now we have demonstrated that this is indeed possible." The current version can only operate over a single night-and-day cycle with sunlight, Kim says, but "continous operation is also possible by utilizing abundant low-grade heat sources such as biomass and waste heat."

The next step, Wang says, is to work on scaling up the system and boosting its efficiency. "We hope to have a system that's able to produce liters of water." These small, initial test systems were only designed to produce a few milliliters, to prove the concept worked in real-world conditions, but she says "we want to see water pouring out!" The idea would be to produce units sufficient to supply water for individual households.

The team tested the water produced by the system and found no traces of impurities. Mass-spectrometer testing showed "there's nothing from the MOF that leaches into the water," Wang says. "It shows the material is indeed very stable, and we can get high-quality water."

Proteins do not function in isolation and their interactions with other proteins define their cellular functions. Therefore, detailed understanding of protein-protein interactions (PPIs) is the key for deciphering regulation of cellular networks and pathways.

These complex networks of stable and transient associations can be studied by affinity purification mass spectrometry (AP-MS) and complementary proximity-based labeling methods such as BioID.

In a study published in the 22th of March issue of Nature Communications, a research team led by Dr. Markku Varjosalo (HiLIFE / Institute of Biotechnology, University of Helsinki) introduce an optimized and integrated approach combining AP-MS and BioID in a single workflow. In addition to just exploiting the advantages of both strategies, the authors show that their approach allows identification and quantification of protein-protein interactions and protein complex stoichiometries; identification of transient or close-proximity interactions with BioID; visualization of the bait protein and the proximal interactors with immunofluorescence microscopy; and defining the molecular context with MS microscopy utilizing the reference dataset obtained by identifying proximal interactors for bona fide subcellular localization markers.

The authors show that using the MS microscopy, it is possible to assign the studied protein to it´s correct cellular or even subcellular location in even higher resolution than with confocal microscopy.

"This study is a continuum of our rigorous efforts in developing new systems biology tools for studying the molecular interactions formed by proteins. We have previously proven that AP-MS is highly reproducible method, which is also suitable for large-scale and inter-laboratory studies", Dr. Varjosalo states. He continues:

"Our newly developed integrated workflow and the reference molecular context proteome map, allows an easy way to probe the molecular localization of (m)any protein(s). The developed MAC-tag and the integrated approach should empower, not only the interaction proteomics community, but also cell, molecular and structural biologists, with an experimentally proven integrated workflow for mapping in detail the physical and functional interactions and the molecular context of proteins in human cells."

Alexandria, VA, USA - At the 47th Annual Meeting of the American Association for Dental Research (AADR), held in conjunction with the 42nd Annual Meeting of the Canadian Association for Dental Research (CADR), Abby Siefker, The Ohio State University, Columbus, presented an oral session titled "The Subgingival Virome in Periodontal Health and Disease." The AADR/CADR Annual Meeting is in Fort Lauderdale, Fla., USA from March 21-24, 2018.

The role of viruses in the etiopathogenesis of periodontitis has been studied for several decades, with equivocal results. This might be attributable to close-ended approaches that used methodologies targeted to single organisms. The purpose of this study was to examine the subgingival virome in periodontal health, chronic periodontitis and aggressive periodontitis, using a whole genome shotgun sequencing approach.

Subgingival plaque samples were collected from deep and shallow sites of 25 subjects with untreated chronic periodontitis (17 which were generalized aggressive and 17 localized aggressive periodontitis) and from 25 periodontally healthy controls. Whole genome sequencing was performed on the Illumina platform, and viral identities were assigned using the Lowest Common Ancestor (LCA) alignment to the M5NR database.

The results show that healthy controls demonstrated lower levels of viruses when compared to diseased subjects. The predominant human viruses were members of the Herpes Simplex family, however bacteriophages were the predominant viral constituents overall.

"Significant differences were observed in the levels of gram-positive and gram-negative phages in health and disease," said Abby Siefker. "While health was dominated by gram-positive phages, especially those belonging to the genera Streptococcus, Enterococcus and Lactobacillus, in disease gram-negative phages predominated. These phages were associated with Prevotella, Burkholderia, Campylobacter, Hemophilus and Aggregatibacter."

Viral load, as well as, specific viral types is higher in disease when compared to health. Similarly, aggressive periodontitis demonstrated higher viral load when compared to chronic, suggesting that studies examining the role of viruses in the etiology of periodontitis are warranted.

INDIANAPOLIS -- The first birth cohort study of its kind has found more than 90 percent of a group of pregnant women in Central Indiana had detectable levels of glyphosate, the active ingredient in Roundup, the most heavily used herbicide worldwide.

Researchers from Indiana University and University of California San Francisco reported that the glyphosate levels correlated significantly with shortened pregnancy lengths.

"There is growing evidence that even a slight reduction in gestational length can lead to lifelong adverse consequences," said Shahid Parvez, the principal investigator of this study and an assistant professor in the Department of Environmental Health Science at the IU Richard M. Fairbanks School of Public Health at IUPUI.

The study is the first to examine glyphosate exposure in pregnant women in the United States using urine specimens as a direct measure of exposure.

Parvez said the main finding of the study was that 93 percent of the 71 women in the study had detectable levels of glyphosate in their urine. "We found higher urine glyphosate levels in women who lived in rural areas, and in those who consumed more caffeinated beverages," he said.

"One thing we cannot deny is that glyphosate exposure in pregnant women is real," Parvez said. "The good news is that the public drinking water supply may not be the primary source of glyphosate exposure, as we initially anticipated. None of the tested drinking water samples showed glyphosate residues. It is likely that glyphosate is eliminated in the water-treatment process. The bad news is that the dietary intake of genetically modified food items and caffeinated beverages is suspected to be the main source of glyphosate intake."

Use of glyphosate is heaviest in the Midwest due to corn and soybean production. Its residues are found in the environment, major crops and food items that humans consume daily.

"Although our study cohort was small and regional and had limited racial or ethnic diversity, it provides direct evidence of maternal glyphosate exposure and a significant correlation with shortened pregnancy," Parvez said.

The magnitude of glyphosate exposure in pregnant women and the correlations with shorter gestation length are concerning and mandate further investigation, he said. "We are planning, contingent upon funding, to conduct a more comprehensive study in a geographically and racially diverse pool of pregnant women to determine if our findings are the same."