Body

BIRMINGHAM, Ala. - After heart attack injury, several fatty-acid-derived bioactive molecules -- including one called resolvin D1 -- play an essential signaling role to safely clear inflammation and help repair heart muscle. The mechanism of how this resolution occurs is not well-understood.

There is a receptor on the surface of many immune cells called ALX/FRP2, and in models of atherosclerosis, ALX/FPR2 is known to act as a sensor to help resolve inflammation.

In a 2015 study using a mouse model, University of Alabama at Birmingham researcher Ganesh Halade, Ph.D., observed that, after heart attack injury, ALX/FPR2 was highly expressed in immune myeloid cells and was activated by resolvin D1 in immune cells in the spleen and in immune cells at the heart attack site. The result was an expedited resolution of the heart attack injury. Resolvin D1 is one of the omega 3 fatty-acid metabolites known as specialized pro-resolving mediators, or SPMs, that help clear inflammation.

Now, Halade and colleagues at UAB, Boston and France have used mice that completely lack ALX/FPR2 to learn more about the pathways this resolution sensor uses to target inflammation. Such knowledge will help in finding treatments to delay the human heart failure that often follows a heart attack.

Before beginning the mouse studies, Halade and colleagues examined heart muscle tissue from patients with heart failure. They found that ALX/FPR2 was plentiful in these human ischemic hearts, and it was located in the cytoplasm of the myocardium cells. In contrast, in healthy human heart tissue, ALX/FPR2 was limited to the cell membrane. To learn more, they then expanded study of the precise and comprehensive role of the resolution receptor using mice having an ALX/FPR2 gene deletion.

The researchers found that mice lacking ALX/FPR2 showed spontaneous, age-related obesity. With the obesity, the ALX/FPR2-null mice developed heart disease that weakened the heart's ability to pump blood, and they had a shortened lifespan with aging. The aging mice also developed kidney inflammation, as shown by increased inflammation markers like NGAL, TNF-alpha and CCL2, and elevated plasma creatinine levels.

After a heart attack in normal mice, leukocyte immune cells in the spleen produce SPMs. However, in the ALX/FPR2-null mice, the researchers found lower levels of SPMs in the heart and the spleen after heart attack, indicative of non-resolving inflammation. Halade says this suggested impaired cross-talk between the injured heart and splenic leukocytes, a cross-talk that is required for the resolution of inflammation. In addition to the lower levels of SPMs, the ALX/FPR2-null mice showed dysregulation of several immune responsive enzymes -- lower levels of LOX enzymes and increased levels of the pro-inflammatory COX-1 and COX-2 enzymes.

Finally, the ALX/FPR2-null mice showed impairment of activated macrophage cells to phagocytose -- that is, to "eat" infecting microbes or dead human cells, one of the macrophage's prime functions. After heart attack, the ALX/FPR2-null mice had increased numbers of neutrophils, the first phagocytic responders after heart injury, in both the spleen and the left ventricle of the heart. Also, there were reduced numbers of reparative macrophages in both the spleen and the heart.

Altogether, says Halade, an associate professor in the UAB Department of Medicine Division of Cardiovascular Disease, these findings demonstrate the integrative role of ALX/FPR2 as a primary target to manage cardiometabolic health, inflammation-resolution processes and cardiorenal syndrome in aging.

Researchers have devised a new plan of attack against a group of deadly childhood brain cancers collectively called diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), thalamic glioma and spinal cord glioma. Scientists at the National Institutes of Health, Stanford University, California, and Dana-Farber Cancer Institute, Boston, identified a drug pair that worked together to both kill cancer cells and counter the effects of a genetic mutation that causes the diseases.

The researchers showed that combining the two drugs - panobinostat and marizomib - was more effective than either drug by itself in killing DMG patient cells grown in the laboratory and in animal models. Their studies also uncovered a previously unrecognized vulnerability in the cancer cells that scientists may be able to exploit to develop new strategies against the cancer and related diseases. The results were published November 20 in Science Translational Medicine.

Matrix screening delivers insights, increases options

DMGs are aggressive, hard-to-treat tumors that represent the leading cause of brain cancer-related death among U.S. children. DMGs typically affect a few hundred children a year between ages 4 to 12; most children die within a year of diagnosis. Most cases of DMG are caused by a specific mutation in histone genes. Histones are protein complexes in the cell nucleus. DNA wraps around histones to form chromatin, which packages DNA in the nucleus. How DNA winds and unwinds around histones is influenced by enzymes, including histone deacetylases. These enzymes add or remove chemical tags, which indirectly controls if genes are turned on or off.

In an earlier study, Stanford neuro-oncologist Michelle Monje. M.D., Ph.D., and her colleagues showed that panobinostat, which blocks key histone deacetylase enzymes, could restore the DIPG histone function to a more normal state. While panobinostat is already in early clinical testing in DIPG patients, its usefulness may be limited because cancer cells can learn to evade its effects. So Monje's team wanted to identify other possible drugs - and combinations of them - that could affect the cancer.

"Very few cancers can be treated by a single drug," said Monje, a senior author of the study who treats children with DIPG and other diffuse midline gliomas. "We've known for a long time that we would need more than one treatment option for DIPG. The challenge is prioritizing the right ones when there are thousands of potential options. We're hopeful that this combination will help these children."

Monje and the National Cancer Institute's Katherine Warren, M.D., now at Dana-Farber Cancer Institute and Boston Children's Hospital, collaborated with Craig Thomas, Ph.D., and his colleagues at the NIH's National Center for Advancing Translational Sciences (NCATS). Thomas and his team used NCATS' drug screening expertise and matrix screening technology to examine drugs and drug combinations to see which ones were toxic to DIPG patient cells.

NCATS' robotics-enabled, high-throughput screening technologies enable scientists to rapidly test thousands of different drugs and drug combinations in a variety of ways. Scientists can examine the most promising single drugs and combinations, determine the most effective doses of each drug and learn more about the possible mechanisms by which these drugs act.

The NCATS researchers first studied the effects of single approved drugs and investigative compounds on DIPG cell models grown in the laboratory from patient cells. They focused on agents that could both kill DIPG cells and cross the brain's protective blood-brain barrier, a necessity for a drug to be effective against DIPG in patients. The team then tested the most effective single agents in various combinations.

"Such large, complex drug screens take a tremendous collaborative effort," said Thomas, also a senior study author. "NCATS was designed to bring together biologists, chemists, engineers and data scientists in a way that enables these technically challenging studies."

While there were multiple, promising outcomes from these screens, the team focused on the combination of histone deacetylase inhibitors (like panobinostat) with drugs called proteasome inhibitors (such as marizomib). Proteasome inhibitors block cells' normal protein recycling processes. The panobinostat-marizomib combination was highly toxic to DIPG cells in several models, including DIPG tumor cell cultures that represented the main genetic subtypes of the disease and mice with cells transplanted from patient tumors. The combination also reduced tumor size in mice and increased their survival. A similar response was found in spinal cord and thalamic DMG models developed from cells grown in culture from patient cells.

Mechanisms at play

The screening studies also provided important clues to the ways the drugs were working. Building on these data, the collaborative team subsequently conducted a series of experiments that showed the DIPG cells responded to these drugs by turning off a biochemical process in the cell's mitochondria that is partly responsible for creating ATP, which provides energy to cells. The drug combination essentially shuts down tumor cell ATP production.

"The panobinostat-marizomib drug combination exposed an unknown metabolic vulnerability in DIPG cells," said first author Grant Lin, Ph.D., at Stanford University School of Medicine. "We didn't expect to find this, and it represents an exciting new avenue to explore in the development of future treatment strategies for diffuse midline gliomas."

Plans are underway for clinical trials of the drug combination and of marizomib alone.

"Many drugs that we test have multiple effects on DIPG cells," said Warren, a senior study author. "Panobinostat, for example, inhibits a specific enzyme, but it has other mechanisms working in tumor cells that may contribute to its effectiveness. We're still trying to understand the various Achilles heels in these cancer cells. This work is an important step in translating our preclinical data into patients."

Monje stressed the panobinostat-marizomib combination might be an important component of a multitherapy strategy, including approaches that harness the immune system and those that disrupt factors in the tumor microenvironment that the glioma cells depend on to grow. Like Warren, Monje emphasized the need to better understand how drugs target and impact the DIPG cells' vulnerabilities.

"Our work with NCATS showed the need to gather more preclinical data in a systematic, high-throughput way to understand and prioritize the strategies and agents to combine," Monje said. "Otherwise we're testing things one or two drugs at a time and designing clinical trials without preclinical data based on hypothesized mechanisms of action. We want to move past this guesswork and provide preclinical evidence to guide clinical decisions and research directions."

Lin added, "The idea is to get as many effective tools as possible to work with that can have an impact on patients."

WASHINGTON--Consuming beans, lentils, peas, and other legumes reduces the risk for cardiovascular disease, coronary heart disease, and high blood pressure, according to a review published in Advances in Nutrition.

Researchers reviewed prospective cohort studies that assessed consumption of legumes on the risk for cardiometabolic diseases and related markers. The study found that those who consumed the most legumes reduced incidence rates for cardiovascular disease, coronary heart disease, and hypertension by as much as 10 percent when compared to those with the lowest intakes.

"Cardiovascular disease is the world's leading--and most expensive--cause of death, costing the United States nearly 1 billion dollars a day," says study co-author Hana Kahleova, MD, PhD, director of clinical research for the Physicians Committee for Responsible Medicine. "This study shows that an inexpensive, accessible, and common pantry staple could help change that: beans."

Beans and other legumes benefit cardiovascular health because they are high in fiber, plant protein, and other micronutrients, but low in fat, free of cholesterol, and low on the glycemic index, according to the study authors.

The Dietary Guidelines for Americans says that Americans are not eating enough legumes and recommends eating about three cups per week. The average American consumes less than a cup a week.

"Americans eat less than one serving of legumes per day, on average," adds Dr. Kahleova. "Simply adding more beans to our plates could be a powerful tool in fighting heart disease and bringing down blood pressure."

Cardiovascular disease is the leading cause of death in the U.S., responsible for approximately 1 in every 4 deaths. About 1 in 3 U.S. adults suffer from hypertension.

Alexandria, VA, USA - 2019 marks the Centennial of the Journal of Dental Research (JDR). Over the last century the JDR has been dedicated to the dissemination of new knowledge and information on all sciences relevant to dentistry and to the oral cavity and associated structures in health and disease. To celebrate, the JDR is featuring a yearlong, commemorative article and podcast series that highlights topics that have transformed dental, oral and craniofacial research over the past 100 years.

The importance and value of behavioral sciences in dentistry has long been recognized and over time behavioral sciences have expanded our understanding of oral health beyond 'disease' to a broader biopsychosocial concept of oral health. In the JDR Centennial article "Behavioral Sciences in the Promotion of Oral Health," Colman McGrath, University of Hong Kong, SAR, China, discusses how this broadened view has led dentistry away from a focus of 'treatment' to oral health 'care.'

"Over the past 100 years, key oral health behaviors have been identified including diet, oral hygiene and dental services, and the relationship between individual factors and the broader environmental factors have been increasingly emphasized, leading to a united call for action in addressing oral health inequalities," said McGrath.

"More recently behavioral therapies, such as cognitive behavioral therapy, are increasingly being employed in dental practice in the management of dental anxiety, pain and psychosomatic dental and oral problems with promising results," said McGrath. "There is a need to consider training for dental professionals, resources and tools for implementation and a systematic approach of what interventions to use, how to employ them, when and for how long, in addition to determining the cost effectiveness and benefits of such approaches."

Accompanying the article, the JDR Centennial podcast "Behavioral Sciences in the Promotion of Oral Health," features a conversation between McGrath and Lois Cohen, Consultant, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA, moderated by JDR Associate Editor Falk Schwendicke of Charite University in Berlin, Germany.

While exercise offers benefits for a wide range of health conditions, it has historically been considered too dangerous for people living with sickle cell disease (SCD). However, a new study published today in the journal Blood adds to mounting evidence that low-to moderate-intensity exercise may be not only safe, but beneficial for these patients.

SCD affects how blood flows through the body. For those with SCD, strenuous physical activity increases blood flow and can lead to serious complications including heart problems and episodes of severe pain known as vaso-occlusive crises. While many patients are advised to avoid all forms of exercise, the new study adds to mounting evidence that lower intensity exercise could actually be helpful.

"When physical exercise is tailored to be light-to-moderate in intensity, the risk of problems is limited," said lead study author Laurent Messonnier, Ph.D., of the Université Savoie Mont Blanc in France. "Performed regularly, this type of exercise may induce beneficial muscle microvascular and functional adaptations that improve patients' physical abilities and quality of life."

The researchers recruited 40 patients with SCD and randomly assigned them to two groups. Half followed their normal lifestyle, which included little physical activity apart from everyday routines such as walking to the bus stop or grocery shopping. The other half participated in an individually tailored regimen of moderate-intensity 40-minute sessions on a stationary bicycle three times per week. Researchers monitored participants' exertion levels closely during each exercise session, tracking circulating oxygen (saturation), blood lactate levels, and perceived exertion to ensure that participants maintained a moderate level of intensity throughout.

After eight weeks, the researchers took biopsies of muscle tissue from participants' thighs. Among the 32 participants for whom complete data were available, the muscle biopsies revealed a significant increase in the density of small blood vessels known as capillaries, the number of capillaries around the muscle fiber, and the surface area through which oxygen and nutrients can flow between blood and muscle in participants who had exercised.

Previous studies have found SCD can cause blood vessels in muscle to become fewer. The changes observed in this study suggest moderate-intensity exercise may help counteract some of these effects, according to researchers, which should improve blood and oxygen delivery to tissues.

Participants in the exercise group also had significant improvements in their muscle function and overall physical ability. Some anecdotally reported improvements in sleep, concentration, and social interactions, as well.

Dr. Messonnier emphasized that further research is needed to understand the benefits--and risks--of exercise in patients with SCD. In this study, no adverse events requiring hospital admission occurred in the training group.

"The recent literature argues in favor of promotion of endurance exercise training for patients with SCD," he said. "However, we need to stay cautious. Before any exercise, people with SCD should be tested and receive professional guidance on what level of exercise will be safe and appropriate."

The study represents an initial attempt to determine whether moderate-intensity exercise is safe, feasible, and potentially beneficial in people living with SCD, but is limited by its small sample size and short duration. Researchers suggested future studies could explore the use of exercise in a larger, more diverse group of participants, determine effects of a longer training period, and investigate the impact of exercise on a broader range of clinical outcomes.

A discovery about how the immune system responds to malaria infection could lead to better treatments for hepatitis C, HIV and lupus, say Australian researchers.

The research team showed, in laboratory models, that strong inflammatory signals caused by malaria infection activate molecules that trigger the production of highly potent antibodies to fight the disease.

The same inflammatory signals are seen in human malaria infections, chronic viral infections and autoimmune disorders. This suggests the discovery could be harnessed to develop new vaccines and therapies that are better able to fight infections such as hepatitis C and HIV, and treat diseases such as lupus.

The research was led by PhD student Ms Ann Ly and Dr Diana Hansen from the Walter and Eliza Hall Institute in Melbourne, Australia, with Institute collaborators Dr Yiang Liao and Associate Professor Wei Shi, and Professor Axel Kallies from the Doherty Institute. It was published today in the journal Cell Reports.

Weak immune response

Dr Hansen and her team have spent the past decade exploring how the host immune system responds to malaria infection. In the past, it was widely assumed that the parasite's ability to evade immune detection was the most important factor in our poor ability to fight malaria infection.

However Dr Hansen said that was only part of the story. "It is well known that an individual must continuously be exposed to malaria over many decades in order to develop protective immunity, during which time they are often sick, as well as spreading the disease," Dr Hansen said.

"We wanted to know what makes malaria infection different to so many other diseases, where a single exposure confers immunity for life."

Malaria experts Ms Ly and Dr Hansen collaborated with immunologist Professor Kallies and bioinformaticians Dr Liao and Associate Professor Shi to answer this question.

Antibodies are key

Antibodies are critical to the immune system's ability to develop long-term immunity to an infection. In 2016, the team showed that inflammatory molecules 'sabotaged' the body's ability to protect itself by hampering the action of helper T cells.

"In our previous paper, we showed that inflammatory signals activated molecules that arrested the development of helper T cells, meaning that B cells did not get the necessary instructions to make antibodies," Dr Hansen said.

"When we began this study, we expected to see that inflammation was also having a negative effect on B cells. In fact, we found the opposite was true. The inflammatory signals were improving the quality of the antibodies produced, by sending B cells to an elite training ground, where they underwent an exhaustive program to become 'professional predators'."

The immune system was not previously known to produce such potent antibodies to malaria infection. So why is the response to malaria infection so poor, requiring decades of exposure?

"What we determined was that inflammatory signals simultaneously improve the quality of the antibody response, while limiting its magnitude. So the B cells, even though they are of elite quality, are not able to have as much impact on future infections."

A target for new treatments

Dr Hansen said she hoped that the discovery would have a role beyond malaria. "I think this discovery is so exciting because of the opportunity it offers in treating chronic viral infections and autoimmune disease," she said.

"We have identified the molecular 'switch' that drives the immune system to produce highly potent antibodies, and the inflammatory signals that influence its function. Targeting this molecule, or other molecules in the same pathway, could offer a more 'precision medicine' approach to treating these diseases than currently exists."

In chronic infections, including malaria and viral infections such as HIV and chronic hepatitis C, producing very high quality, potent antibodies is critical for clearing the infection. On the flip side, B cells that are primed to make antibodies that target self-antigens - our body's own proteins and tissues - are incredibly destructive, leading to autoimmune diseases such as lupus.

"The hope is that we would be able to create vaccines or therapies that would 'switch on' molecules that help to produce these elite B cells to fight chronic infections better, or 'switch off' the same molecules in autoimmune diseases to stop the production of B cells, such as in lupus," said Dr Hansen.

What The Study Did: Adults experiencing a migraine of moderate or severe severity took the drug ubrogepant or placebo and reported if after two hours they were free of pain and of their most bothersome migraine-associated symptom in this randomized clinical trial.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Richard B. Lipton, M.D., of the Albert Einstein College of Medicine in Bronx, New York, is the corresponding author.

(doi:10.1001/jama.2019.16711)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

A new study in JNCI Cancer Spectrum finds that exposure to radiation from CT scans is associated with higher risks of developing thyroid cancer and leukemia.

Researchers here conducted study from a National Health Insurance dataset in Taiwan between 2000 and 2013. The study followed 22,853 thyroid cancer, 13,040 leukemia, and 20,157 non-Hodgkin lymphoma cases. Researchers consulted data from the National Health Insurance program to study demographic and medical information on disease diagnoses, procedures, and drug prescriptions, and the enrollment profiles of all patients. Patients were excluded if they were under 25 years at the time of the cancer diagnosis, had less than three years of follow-up before cancer diagnosis, or had a history of a cancer before the year 2000.

Results showed that patients who developed thyroid cancer and leukemia had significantly higher likelihood of having received CT scans. In studies that combined patients across age groups, exposure to medical CT scans was not associated with increased risk for non-Hodgkin lymphoma. However in patients between 36 and 45 years of age, there was a three-fold increased risk of non-Hodgkin lymphoma associated with CT scans. In older patients the association between exposure to CT scans and non-Hodgkin lymphoma was not evident.

Researchers concluded that patients receiving CT scans had in general marked increases in the risk of developing thyroid cancer and leukemia, especially in female patients and patients younger than 45.

"Our study found that CT scans are associated with an increased risk of thyroid cancer and leukemia in adults in all ages and with non-Hodgkin lymphoma in young adults," said Yu-Hsuan Joni Shao, one of the paper's authors. "The risk is stronger in patients who have higher cumulative doses from multiple scans. The increased numbers of people undergoing CT scans have become a public health issue."

PHILADELPHIA, PA - Health campaigns on social media aimed at increasing human papillomavirus (HPV) vaccination may see greater success, according to Drexel University researchers, if they inject a narrative into information-based posts.

In a study published today in the journal Health Education and Behavior, researchers from Drexel's Dornsife School of Public Health analyzed 360 randomly selected Instagram posts from a pool of 3,378 English-language posts about HPV vaccination. Although the majority of posts were pro-vaccine (56 percent), anti-vaccine messages -- the majority of which featured a narrative structure -- experienced much higher engagement, including more "likes" (24 vs 86 "likes," on average). The team's findings on the value of narratives in increasing social media engagement could guide public health communications efforts, and are among the first to look at HPV vaccine-related content on Instagram.

The majority of pro-vaccine posts - 61 percent - shared actionable information about the vaccine, while only 45 percent featured personal narratives (i.e., elements of a story). Researchers suggest that pro-vaccine posts may garner greater engagement if they continue to provide information and evidence, while communicating this through a more narrative structure.

The current Drexel study helps researchers understand how broad these anti-vaccine sentiments are on Instagram. It also yields insight into how these commonly used messaging strategies may have a different appeal compared to pro-vaccine messages. The authors see great opportunity for communicating health information on Instagram. More than a third of United States adults, and 71 percent of those ages 18-24 use the platform, according to a 2018 Pew Research Center report.

"In recent years, we're seeing a resurgence of misleading anti-vaccination messages and related misinformation spreading through social media," said senior author Philip M. Massey, PhD, an associate professor of community health and prevention in the Dornsife School of Public Health. "By studying what makes these messages so effective online, we can improve fact-based, pro-vaccination messaging aimed at improving public health."

The benefits of the HPV vaccine in the prevention of a number of cancers in boys and girls are well-documented, yet the anti-vaccine movement has gained ground in recent years through "bots" and efforts by groups to spread false information through online communities, according to a 2017 study in the journal Human Vaccines and Immunotherapeutics.

HPV is the most common sexually transmitted infection in the United States and can cause six different types of cancer in women and men, including nine out of every 10 cases of cervical cancer and seven out of 10 oral cancers, according to the Centers for Disease Control and Prevention (CDC).

The CDC recommends that all children ages 11-12 receive the vaccine. If the first dose is received before age 15, only two doses are needed (it's three doses if they start later in life). Despite these recommendations and established success of the vaccine at preventing cancer-causing HPV, just over half of those eligible are fully up-to-date on vaccination, according to an August 2019 CDC report.

This research adds to a growing volume of work looking at social media's impact on the public health push for HPV vaccination. In recent related studies, Massey and his colleagues analyzed nearly 200,000 tweets about HPV vaccination and found that 39 percent of tweets were positive, while only 25 percent were classified as negative.

The researchers also published a study in February 2018 offering insights on how and when health professionals tweet about the HPV vaccine. They are now embarking on NIH-funded research to build on those findings. Specifically, the team plans to use large-scale data to determine whether narrative Twitter posts increase HPV vaccination more effectively than non-narrative posts.

People with prosopagnosia, or "face blindness," have trouble recognizing faces -- even those of close friends and family members. It often causes serious social problems, although some people can compensate by using clothing and other cues. Face blindness often becomes apparent in early childhood, but people occasionally acquire it from a brain injury later in life. A new study of people who became face-blind after a stroke, led by Alexander Cohen, MD, Ph.D., of Boston Children's Hospital, provides clues to what goes wrong in the brain.

The findings, published in the journal Brain, indicate that no one single area is always perturbed in face blindness. Instead, face blindness involves an entire network, where a malfunction in communication among the various components can bring the system down. This potentially opens the door for improving face recognition by tweaking the function of different parts of the network.

Cohen, first author on the paper, believes the findings could also apply to other people with poor face-processing abilities, specifically individuals with autism, who often score very poorly on tests of face processing.

From autism to stroke and back again

Cohen began by speculating that autism could be approached not just as a holistic entity, but by studying its individual symptoms. Those symptoms have a better chance of being localized to specific parts of the brain and could perhaps be turned into biomarkers and treatment targets.

That's where face blindness comes in. It's easy to test for and common in autism, seen in children as young as 2.

"In eye gaze studies, autistic kids often don't look at the faces in a video," Cohen says "Or they just look at one part, often the mouth, maybe because it's giving more information about speech. Many find eye contact uncomfortable."

Data suggest that the worse people with autism are at face processing, the worse their social communication.

"The question is, are face processing deficits causal in autism, or do they result from autism?" says Cohen. "That's where looking at face processing in people with stroke really helps. They have specific lesions in the brain, so there is more of a cause-and-effect relationship. If you find an abnormality involving the same brain areas in a child with autism, there's a much higher chance that it may be driving the face processing deficit."

Mapping brain networks

Face blindness has previously been linked to the brain's right fusiform face area (FFA), but not everyone with face blindness shows damage there. Cohen searched the medical literature and identified 44 people from 19 studies who developed face blindness after a stroke and who also had brain MRI data available.

Of the 44 lesions causing face blindness, only 29 involved the right FFA; the other 15 did not. To try to explain these cases, Cohen used a new method, developed by senior study author Michael Fox, MD, Ph.D., of Beth Israel Deaconess Medical Center, that draws on data from functional MRI images to create a large-scale map of brain networks, showing the relationships between different brain areas. With it, Cohen could determine which networks were consistently injured in the stroke patients that developed face blindness.

The 15 lesions that did not involve the FFA, Cohen's team found, were in areas that were functionally connected to the right FFA, meaning that they are typically used when the FFA is being used, and become quiet when the FFA is quiet.

Surprisingly, all 44 lesion locations were also negatively connected with four additional areas in the left frontal cortex -- meaning that brain activity in the four areas goes down when activity in the lesion locations goes up, and vice versa. Intriguingly, all four of the new areas belong to the left frontoparietal control network, which attends to specific features of a visual stimulus.

Based on the findings, Cohen speculates that face recognition involves two distinct brain networks. It's not yet clear whether face blindness results from both networks being disrupted, or from an imbalance between the two.

"Maybe in face blindness, you're using too much detail information, and are not looking at the face as a whole," Cohen says. "That exact imbalance is something that has been seen in autism. Or, maybe you need both kinds of information to recognize a face."

Mapping face processing in tuberous sclerosis

Based on the stroke data, Cohen now plans to delve back into face processing problems in autism spectrum disorder. Under a $100,000 two-year research award from the Child Neurology Foundation, Cohen will study children with tuberous sclerosis complex (TSC), a genetic syndrome that often includes autism and atypical face processing.

Most children with TSC have tubers (noncancerous tumors) in their brains that are thought to affect the function of nearby brain tissue. To see if they have any relationship with face processing, Cohen will recruit up to 80 children with TSC, locate their brain tubers, administer tests of face processing, and map their brain networks. He will then compare the findings with his data from the stroke study to see if common brain areas are involved.

Could face blindness be treated?

Eventually, Cohen hopes to do a larger study of brain connectivity and face processing in children with garden-variety (non-syndromic) autism. "Just as many disorders can be affected by multiple genes, it may take a whole network of brain regions to cause a symptom," he says.

If all roads in that network lead to a specific area in the brain, that area could potentially be treated by methods to increase or decrease its activity. Even addressing face processing in isolation could improve the quality of life in children with autism -- and others with face blindness.

"We could try to modulate activity in that spot -- with novel therapies like transcranial magnetic stimulation or functional-MRI-based neurofeedback -- and see if it affects behavior," Cohen says. "If this works, we aim to expand this methodology to many other symptoms in autism as well."

Echocardiography is a test that uses ultrasound techniques to produce images of the heart in real time. Stress echocardiography uses this technique to evaluate the heart rate response while performing an activity in which the heart has to work (stress). Stress echocardiography can reveal traces of cardiovascular disease in its early stages, before it manifests, and so this technique becomes a valuable screening tool.

A protocol of stress echocardiography that has proved to have advantages in the clinical practice is obtained while performing handgrip exercises. However, the maximal exercise levels are not easily quantified and regulated, requiring the analysis of the complete data sequences (thousands of images), which poses a challenge for the clinician.

An analytical framework is proposed that explicitly addresses the practical challenges posed by analysing thousands of complete data and illustrates the potential of their study on a specific group of heart patients

A study published in the journal Medical Image Analysis, proposes an operational framework for the analysis of this complex dataset. The article has just been published, on 6 November, in the advanced online edition. In this study, the physiological data of heart function are obtained by echocardiography while subjects performed a series of handgrip exercises. The data were integrated by Multiple Kernel Learning (MKL).

The study was coordinated by Bart Bijnens (ICREA-UPF) and Gemma Piella, researchers of the Physense and SiMBioSys research groups, respectively, which belong to the BCN MedTech research unit at the Department of Information and Communication Technologies (DTIC) at UPF who work in the field of Machine Learning for clinical decision-making. Mariana Nogueira and Mathieu De Craene are the first authors of the article and researchers at Medisys Philips Research in Paris (France) within the framework of the CardioFunXion project. Sergio Sánchez Martínez is co-author and a member of SiMBioSys; Devyani Chowdhury, co-author of the study and a researcher at the University of Pennsylvania (USA).

An analytical framework based on machine learning

The authors propose an analytical framework that explicitly addresses the practical challenges posed by analysing thousands of complete data and illustrates the potential of their study on a specific group of heart patients. The article presents the results of image acquisitions obtained from 15 patients, 10 healthy and 5 with the ANT1 (Adenine Nucleotide Translocator-1) mutation, which affects cardiac cycles. For the study, the researchers analysed a total of 1,377 cardiac cycles.

"Our framework uses Multiple Kernel Learning (MKL) to project heterogeneous data retrieved during each cardiac cycle during the stress test in a low-dimensional space where the main data variations are encoded. Here, the stress response of each subject can be seen as a trajectory, and from the similarity between trajectories, the subjects can be allocated to groups that reflect different response patterns", Bijnens and Piella explain.

MKL provides a simplified representation that is explored to discriminate groups of response and understand the underlying pathophysiological mechanisms

Then, the authors explain, the physiological interpretation of the results is decoded allowing reconstructing the input signals along any trajectory through the low-dimension output space. This simplified representation is explored to discriminate groups of response and understand the underlying pathophysiological mechanisms.

The authors have proposed a framework for analysing nonstandardized stress echocardiography sequences. Using unsupervised MKL, they combined the information on the myocardial velocity and heart rate to obtain a lower-dimensional representation of the data. The proposed framework is illustrated in the sequences of handgrip exercises acquired in a control group of healthy subjects and patients with the ANT1 mutation.

The results show that the methodology proposed by these experts in machine learning is able to discriminate between different responses and provide information about the underlying pathophysiological mechanisms, demonstrating its ability to analyse such complex datasets showing the potential of nonstandardized protocols, such as handgrip exercises to unmask differential cardiac response mechanisms. Indeed, the results confirm that the proposed framework is able, for each study subject, to distinguish healthy or pathological responses and record pathology-specific patterns.

Zoology researchers from Trinity College Dublin, working with the Department of Agriculture, Food and The Marine (DAFM) and the National Parks and Wildlife Service (NPWS), have unlocked the secrets of dispersing badgers.

Their research has major implications for implementing vaccination programmes to limit the spread of bovine tuberculosis (TB).

The findings come at an opportune time, as DAFM has commenced rolling out a national programme to vaccinate badgers in its efforts to eradicate TB.

Badgers are a protected species and are one of Ireland's most iconic wild creatures, but they can harbour TB and inadvertently transfer it to cattle. Infected cattle must be culled, which results in the loss of millions of euro each year in the agricultural sector, which can devastate individual farmers and their families.

Vaccinating badgers against TB provides an excellent option to mitigating these risks, but to do that effectively, it is imperative to understand how badgers move around in the wild and to target those most likely to spread disease. Badgers are social animals, living together in a shared territory. Dispersal is when a badger "moves house" e.g. it goes from living with one social group to living with an entirely different social group in a new location.

In the research, just published in leading international journal Ecology and Evolution, the zoologists describe the process of dispersal in greater detail than ever before after trapping and vaccinating 139 badgers, and monitoring their movements closely.

Aoibheann Gaughran, Postdoctoral Researcher in Trinity's School of Natural Sciences, was the lead author on the paper. She said:

"We found that only 17% of the badgers we tracked dispersed, so it's fair to say most badgers don't leave home - they remain living in the territory where they are born. However, some of those that did move away went on unexpectedly long and complex journeys."

"By using GPS satellite trackers to take a uniquely personal look at the nightly comings and goings of 80 of these badgers in the wild, we discovered that some - particularly the females - could cover over 100km while wandering around large areas looking for their new home. Our record-holder was a female that settled down only 1.5km away from where she was born, but travelled 308km back and forth before she joined her new social group. Male badgers, on the other hand, liked to stay close to their Mammy, and typically just moved next door."

"Dispersal begins when badgers are aged one year or older, but by vaccinating them as cubs we can avoid the disease-spreading implications of this behaviour."

The zoologists hope that by better understanding when and how badgers move between territories, they will be able to pinpoint where the greater risks for TB transmission lie, which would be extremely valuable information from a disease control perspective.

Nicola Marples, Professor of Zoology at Trinity, said:

"This research on badger movement should help to maximise the efficiency and effectiveness of the impending badger vaccination programme, which is great news. From both conservation and disease-control perspectives, a well-designed vaccination programme should provide a win-win situation."

The research was part of a collaboration between the Department of Food, Agriculture and the Marine, the National Parks and Wildlife Service and the Trinity zoologists, and was funded by DAFM.

BOSTON- Yoga and physical therapy (PT) are effective approaches to treating co-occurring sleep disturbance and back pain while reducing the need for medication, according to a new study from Boston Medical Center (BMC). Published in the Journal of General Internal Medicine, the research showed significant improvements in sleep quality lasting 52 weeks after 12 weeks of yoga classes or 1-on-1 PT, which suggests a long-term benefit of these non-pharmacologic approaches. In addition, participants with early improvements in pain after 6 weeks of treatment were three and a half times more likely to have improvements in sleep after the full, 12-week treatment, highlighting that pain and sleep are closely related.

Sleep disturbance and insomnia are common among people with chronic low back pain (cLBP). Previous research showed that 59% of people with cLBP experience poor sleep quality and 53% are diagnosed with insomnia disorder. Medication for both sleep and back pain can have serious side effects, and risk of opioid-related overdose and death increases with use of sleep medications.

"Identifying holistic ways to treat these conditions could help decrease the reliance on these medications as well as keep patients safer and more comfortable," said Eric Roseen, DC, MSc, a researcher in the department of family medicine at BMC, who led the study.

The randomized controlled trial included 320 adults with cLBP from BMC and seven surrounding community health centers. At the beginning of the study, over 90 percent of participants with cLBP were found to suffer from poor sleep. Participants were assigned one of three different therapies for cLBP: physical therapy, weekly yoga, or reading educational materials. Previous research from BMC discovered that yoga and PT are similarly effective for lowering pain and improving physical function, reducing the need for pain medication. In this study, results for sleep improvements were compared over a 12-week intervention period and after 1 year of follow-up.

"The high prevalence of sleep problems in adults with chronic low back pain can have detrimental effects on a person's overall health and well-being," said Roseen, also an assistant professor of family medicine at Boston University School of Medicine. "This really emphasizes the need for providers to ask patients with chronic low back pain about the quality of their sleep. Given the serious risks of combining pain and sleep medications, nonpharmacologic approaches should be considered for these patients."

Genetically targeted drugs and immunotherapies are transforming the way we treat many forms of lung cancer. However, a University of Colorado Cancer Center study published in the Journal of the National Cancer Institute shows that while the use of these drugs rose 27 percent from 2007 to 2015, new, high-cost lung cancer drugs are not used equally in all places, with all patients. Patients who lived in high-poverty areas were 4 percent less likely to be treated with high-cost lung cancer drugs. On the other hand, patients treated at National Cancer Institute-designated cancer centers were 10 percent more likely to be given these drugs than were patients treated in other settings.

"Without these drugs, they may not have the same outcome as those who receive treatment. Some of these drugs have the potential to increase the lifespan of cancer patients," says Cathy J. Bradley, PhD, CU Cancer Center Deputy Director and Associate Dean for Research at the Colorado School of Public Health.

Bradley suggests that in addition to the socioeconomic disparity in the use of these drugs, the fact that they are used more often at NCI-designated cancer centers also implies a disparity between research-oriented treatment centers and those that are not.

"If you live in a rural area, it can be challenging to access an NCI-designated cancer center where these drugs are more commonly used. And even if you are in an urban area and didn't go to an NCI center, you also were less likely to get these drugs," Bradley says.

The study examined the data of Medicare patients from 2007-2015, exploring how race/ethnicity, urban or rural residency, poverty, and treatment facility type were associated with the use of drugs costing more than $5,000 per month in patients diagnosed with metastatic (stage IV) non-small cell lung cancer. Medicare spending during the 12 months following diagnosis was lower for rural patients by about $17,000 per patient.

"There is an underlying concern about whether the widespread use of these high-cost drugs is sustainable. But leaving aside the question of Medicare's affordability and sustainability, what we're seeing in the use of these agents is problematic. Our findings suggest that uneven access to specialized care due to poverty or living in remote areas may explain some of the observed disparities," says paper co-author Marcelo Perraillon, PhD.

Currently the Centers for Medicare and Medicaid are forbidden by law to negotiate prescription prices with drug manufacturers. Likewise, the Federal Food and Drug Administration is disallowed to take into account a drug's price when considering approval (unlike its counterpart in Europe, the European Medicines Agency). These factors among many others mean that as new and more expensive anti-cancer agents are developed, the cost to society as a whole and to individuals who pay indirectly for the use of these drugs through insurance premiums increases, without taking into account increases in drug effectiveness that could establish the value added by the new drugs.

"The societal cost of these medications doesn't mean that they are not worth it," Perraillon says, indicating that the current paper did not study whether the high cost of these medications is justified. "Our study does not say whether prescribing these agents is good or bad. What it means, and what we show, is that location or income should not hinder the use of these agents by some."

The liver performs several critical functions including filtering blood, detoxifying chemicals and metabolizing drugs. When the liver is damaged by hepatitis, alcohol, or primary liver disease, fibrosis ensues. Long-term fibrosis contributes to cirrhosis of the liver, which in turn can cause severe complications, including hepatic encephalopathy (HE), a condition that results in a temporary decline in mental function in up to 70% of patients with cirrhosis.

The current dogma for patients that present with HE symptoms is to obtain a blood ammonia test because ammonia is used as a traditional HE marker. Patients are then treated with lactulose to reverse the HE symptoms. However, a recent study by researchers at the Medical University of South Carolina (MUSC) challenges this standard practice. The work, published online on October 14 by The American Journal of Gastroenterology, clearly demonstrated that ammonia levels do not dictate the management of HE.

"The study shows that while ammonia is commonly used, it is simply not helpful when we treat patients," says Don C. Rockey, M.D., professor and chair of the Department of Medicine at MUSC. "Drawing an ammonia level may be helpful in certain unusual diagnostic situations, but despite current practice which is to obtain ammonia levels in patients with cirrhosis, we don't use it to treat patients."

MUSC was uniquely poised to conduct this retrospective study because MUSC is one of the few academic medical institutions that teaches new trainees not to perform ammonia tests on cirrhotic patients presenting with HE. Therefore, the study included two cohorts of patients, those who had their blood ammonia levels measured and those who did not. Comparing these two cohorts provided valuable information about the therapeutic value of this test.

The results showed that the absence or presence of abnormal ammonia levels did not impact lactulose treatment. Furthermore, there was no difference in treatment between cirrhotic patients who had their ammonia levels measured and those who did not. Regardless of the ammonia level, cirrhotic patients that presented with HE received the same lactulose treatment regimen. The researchers concluded that performing the ammonia test was a waste of blood, money and resources.

"The bottom line is that ammonia levels are not helpful in management of patients with cirrhosis and HE," says Rockey.

Patients who experience an HE incident are at increased risk for future incidents and are therefore prescribed a regimen of daily lactulose therapy. However, patients often fail to take lactulose because of its taste and it may cause diarrhea. An alternative medication, rifaximin, is prohibitively expensive for some patients and is thus often discontinued. Because of this, HE is the most common indication for admission in cirrhotic patients.

The new study does not suggest that doctors should abandon all ammonia testing.

"There are some specific circumstances where an ammonia test might be useful, but in routine management of HE caused by cirrhosis, it is not helpful," says Rockey. Some of these circumstances include a urea cycle defect or an unknown diagnosis of HE.

In summary, ammonia levels failed to predict the severity of disease and did not guide the clinical management of HE.