Culture

Ann Arbor, March 26, 2018 - Drug-related deaths have grown to be a major US public health problem over the past two decades. Between 2006 and 2015 there were more than 515,000 deaths from drug overdoses and other drug-related causes. The economic, social, and emotional tolls of these deaths are substantial, but some parts of the US are bearing heavier burdens than others. Evidence from the first national study of county-level differences suggests that addressing economic and social conditions will be key to reversing the rising tide of drug deaths, reports the American Journal of Preventive Medicine.

"The drug epidemic is a pressing concern among policymakers," noted Shannon M. Monnat, PhD, Associate Professor of Sociology and Lerner Chair for Public Health Promotion, Maxwell School of Citizenship and Public Affairs, Syracuse University, Syracuse, New York, USA, who conducted the study. "The media portrayal of the drug overdose epidemic has largely been that it is a national crisis. However, drug deaths are not randomly distributed across the US. My analyses show that some places in the US have much higher drug mortality rates than others."

Using data from the US Centers for Disease Control and Prevention (CDC) Multiple-Cause of Death Files (2006-2015), US Census Bureau, US Department of Agriculture Economic Research Service, Agency for Healthcare Research and Quality, and Northeast Regional Center for Rural Development, the study modeled associations between county-level drug-related mortality rates and economic, social, and healthcare environments.

Analysis showed the average county-level age-adjusted drug-related mortality rate was 16.6 deaths per 100,000 population, but there were substantial geographic differences with drug-related deaths reaching over 100 per 100,000 in some counties. There was significant spatial variation in rates.

High mortality rate clusters in Appalachia, Oklahoma, parts of the Southwest, and northern California

Low mortality rate clusters in parts of the Northeast, the Black Belt, Texas, and the Great Plains

Substantial within-state variation with West Virginia having the largest disparity between the highest and lowest rate counties

Average mortality rates were significantly higher in counties with greater economic and family distress and in counties economically dependent on mining. Counties at the highest level of family distress (divorce/separation and single parent families) had an average of more than eight more drug-related deaths per 100,000 population than counties at the lowest level.

Average mortality rates were significantly lower in counties with a larger presence of religious establishments, a greater percentage of recent immigrants, and counties with economies reliant on public (government) sector employment.

On average, there were no differences in mortality rates between rural and urban counties, but some rural counties, especially those in Appalachia, have the highest mortality rates in the country. Healthcare supply factors did not contribute to the differences between county mortality rates.

According to Dr. Monnat's findings, social and economic environments are important for prevention because they affect stress, healthcare investment, residents' knowledge about and access to services, self-efficacy, social support, and opportunities for social interaction.

"We need to get real with ourselves about the US drug problem," explained Dr Monnat. "We are not going to Narcan our way out of this. Opioids are a symptom of much larger social and economic problems. Just as other chronic diseases have underlying social determinants, addiction is also a social disease. 'Addiction does not discriminate' is a soundbite that ignores the reality that overdose rates are highest in economically distressed communities, particularly places that have experienced declines in job opportunities for people without a college degree. Addressing economic and social conditions will be key to reversing the rising tide of drug deaths."

A study undertaken by British American Tobacco has shown that teeth exposed to cigarette smoke over a period of 2 weeks became very discoloured very quickly, whereas teeth exposed to e-cigarette vapour or vapour from glo, a tobacco-heated product, did not (Figure 1). After 2 weeks of almost continuous exposure, these teeth were almost indistinguishable from teeth that were not exposed to anything at all.

Smokers get 'stains', turning teeth from a healthy-looking white to an unhealthy-looking yellow/brown colour. Although this staining is commonly referred to as nicotine staining, it is not caused by nicotine, but by tar in smoke.

As part of a wider study on oral health, scientists at British American Tobacco studied discoloration in teeth. A prototype Vype e-cigarette and a tobacco heating product, glo, were assessed for tooth discoloration and the impact on teeth compared to that of cigarette smoke.

A puffing robot was used to puff on the products to produce smoke and vapour. In each case, the smoke or vapour was collected onto a filter pad (Figure 2) and then a solvent was used to extract the solid material from the filter pad. The impact of the extracted material (extract) on tooth discoloration was then tested using cows' teeth.

Cows' teeth are routinely used in laboratory experiments in lieu of human teeth. They are used for example to test oral hygiene products like toothpaste and mouthwash.

The teeth were prepared by polishing them using fine sandpaper to create a surface more like that of human teeth. The teeth were then incubated at body temperature in human saliva to create an environment mimicking that in the human mouth. This incubation results in the creation of the so-called pellicle layer on the teeth, which is the smooth film you can feel on your teeth when you rub your tongue over them. It is the normal protein layer that forms on teeth when certain molecules in saliva bond to the tooth enamel.

The teeth were incubated in an oven at body temperature and exposed to the various extracts from the cigarette smoke or e-cig or THP vapour. Some teeth were also incubated in solvent with no extract at all to act as a control/blank.

After the first day, the teeth exposed to the smoke extract started to change colour and over the course of 14 days, these teeth got darker and darker in colour. Even with the naked eye, the colour changes with the cigarette extract could be easily seen after 1 day. The exact colour change was also measured in the laboratory using a special camera that can detect tiny changes in hue. In contrast to teeth exposed to smoke those exposed to e-cigarette or THP vapour exhibited minimal change in colour, similar to untreated teeth (Figure 1).

CINCINNATI -- Results of an analysis from the University of Cincinnati (UC) College of Medicine show that additional therapy, or adjuvant therapy, delivered after surgical removal of a rare type of gastrointestinal tumor does not increase survival rates for patients.

These findings, being presented Saturday, March 24, 2018, at the Society of Surgical Oncology Annual Cancer Symposium in Chicago, provide insight on treatment plans for patients with these types of tumors possibly eliminating the need for prescribed adjuvant therapy, preserving quality of life and saving money.

"Due to a lack of randomized clinical trials, the role of adjuvant therapy in the treatment of patients with surgically removed ampullary tumors is poorly defined," says Vikrom Dhar, MD, a surgical resident at UC and co-principal investigator on the study along with Syed Ahmad, MD, professor of surgery and director of the Division of Surgical Oncology for the UC College of Medicine. Ahmad is also a UC Health surgical oncologist and director of the UC Cancer Institute's Pancreatic Disease Center.

Ampullary cancer is a cancer that arises from the ampulla of Vater, which is where the bile duct and pancreatic duct come together and empty into the small intestine. Ampullary cancers often block the bile duct while they're still small and have not spread far. This blockage causes bile to build up in the body, which leads to yellowing of the skin and eyes (jaundice). Because of this, these cancers are usually found earlier than pancreatic cancers, and they usually have better outcomes.

For this study, researchers used the American College of Surgeons National Cancer Database to identify patients with ampullary tumors, stage I through III, which had been surgically removed between 1998 and 2006 (5,298 patients). Patients receiving surgery alone (3,785), surgery with additional chemotherapy (316), and surgery with additional chemotherapy and radiation therapy (1,197) were compared. Analyses taking into account one variable and/or many variables were used to determine overall survival rates for patients.

"Over the study period, 29 percent (1,513) of patients who had their ampullary tumors surgically removed received adjuvant therapy; adjuvant therapy was more often used in patients with stage III disease, cancer in their lymph nodes and positive surgical margins, meaning cancer in the tissues surrounding the removed tumor after surgery," Dhar says. "However, no significant differences in stage-specific survival were noted between patients receiving any treatment for stages I, II or III of the disease. Similarly, no survival benefit was found for patients with positive resection margins or cancer in their lymph nodes who were receiving adjuvant therapy."

"This national analysis demonstrates that adjuvant therapy for surgically removed ampullary tumors, even when used in patients with aggressive disease, does not show any survival benefit," he adds. "Further studies evaluating subtypes of the cancer, and how they differ on a cellular level, as well as evaluating the effect of newer systemic therapies are needed. However, these results could lead to a new standard of care for patients with this type of cancer, regardless of the stage of the disease."

Researchers cite no conflicts of interest.

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."