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An international group of researchers led by Prof. Jan Cools of the VIB-KU Leuven Center for Cancer Biology have made a breakthrough in understanding the development of acute lymphoblastic leukemia, an aggressive cancer of the blood. While scientists were already familiar with many cancer-causing genes and their separate functions, the VIB team has now illustrated how two of these cancer genes work together to trigger leukemia. Their insights are published in the scientific journal Cancer Discovery.

Acute lymphoblastic leukemia (ALL) is the most commonly occurring cancer in children, with 100 new cases reported in Belgium every year. Despite the efficacy of chemotherapy in treating this disease, its long and short-term side effects are considerable. The team of Prof. Jan Cools pursued this research project to learn more about how cancer genes interact with each other, with the goal of identifying alternative therapy options that don't cause severe side effects.

Characterized by specific mutations

ALL is caused by the accumulation of genetic changes (mutations) that alter the behavior of developing immune cells that transform them into aggressive leukemia cells. Recent studies have found that ALL cases are often characterized by mutations in a certain gene pathway, called JAK3/STAT5.

Prof. Jan Cools (VIB-KU Leuven): "JAK3/STAT5 mutations are important in ALL, since they stimulate the growth of the cells. However, leukemia patients have additional gene mutations, and we found that JAK3/STAT5 mutations, frequently occur together with HOXA9 mutations."

Connecting the genetic dots

In this study, Jan Cools and his team created a mouse model with cancer-associated JAK3/STAT5 and HOXA9 mutations to determine if they cooperate to drive the development of ALL. HOXA9 mutations have a well-established role in leukemia development.

Dr. Charles de Bock (VIB-KU Leuven): "We examined the cooperation between JAK3/STAT5 mutation and HOXA9. We observed that HOXA9 boosts the effects of other genes, leading to tumor development. As a result, when JAK3/STAT5 mutations and HOXA9 are both present, leukemia develops more rapidly and aggressively."

The team's identification of a direct cooperation between these two cancer genes paves the way for targeted treatments - not only in ALL, but also in other leukemias where JAK3/STAT5 could cooperate with HOXA9.

Philadelphia, March 20, 2018 - Steroids are currently the only available treatment to reduce the repetitive cycles of inflammation and disease progression associated with functional deterioration in patients with muscular dystrophy (MD). A study reported in the American Journal of Pathology showed that a new treatment approach using the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene significantly improved cardiac, respiratory, and skeletal muscle functions and increased bone density in both male and female mice with the same gene defects as a subset of patients with MD.

"Our results show that there are two important advantages of tamoxifen and raloxifene treatment over steroids, which have limited benefits for patients with MD. First, the SERMs improve both histology and function of all muscles; although steroids improve histology, they improve function to a much lesser extent. Second, SERMs enhance bone density, whereas steroids exacerbate osteoporosis and increase the risk for fractures," explained Qi Long Lu, MD, PhD, director of the McColl-Lockwood Laboratory for Muscular Dystrophy Research, Neuromuscular/ALS Center, Department of Neurology, Atrium Health's (formerly Carolinas HealthCare System's) Carolinas Medical Center, Charlotte (NC).

The mice used in this study have the identical gene defects and show almost the same disease manifestation as patients with MD and are therefore an excellent model for therapeutic evaluation. Investigators administered tamoxifen (2, 10, or 50 mg/kg), raloxifene (50 or 100 mg/kg), or saline to mutant mice with dystroglycanopathy, a form of MD, for up to a year, beginning at three weeks of age.

The investigators found several indicators that tamoxifen and raloxifene delay or even halt disease progression. Within one month, treatment with either SERM reduced muscle pathology with significant reduction in the numbers of degenerating fibers. After a year, control mice showed high variation in fiber size with focal inflammatory infiltrations, but these dystrophic changes were much less evident after tamoxifen or raloxifene. A noticeable reduction in collagen accumulation in limb muscles for all treatment groups vs controls was observed. Importantly, treatment with SERMs clearly mitigates muscle damage and enhances functions of both respiratory and cardiac muscles in addition to the limb muscles.

Other benefits were also observed. Control mice showed progressive muscle degeneration and regeneration in the diaphragm, accompanied by increasing fibrosis and infiltration, as well as significant impairment in respiration. Both tamoxifen and raloxifene eliminated focal infiltration and reduced the extent of fibrosis in the diaphragm, increased mass, and improved breathing ability. "Both treatments also improved bone density in the tibia and femur, potentially reducing the risk of fracture, a major threat to patients as MD progresses," added co-author Bo Wu, PhD, a research scientist at the McColl-Lockwood Laboratory for Muscular Dystrophy Research, Neuromuscular/ALS Center, Department of Neurology, Atrium Health's (formerly Carolinas HealthCare System's) Carolinas Medical Center, Charlotte (NC).

These histological changes were accompanied by functional improvements. For example, SERM treatment improved grip strength of both forelimb and hindlimb muscles and enhanced running ability on a treadmill test depending on the dose.

Sex-related differences in the effects of tamoxifen and raloxifene warrant careful consideration if the drugs are to be administered clinically for MD, noted the investigators. This is not surprising since SERMs act on estrogen receptors and interact both as estrogen-receptor agonists and antagonists.

"SERM therapy has great potential to significantly delay or halt MD progression. With the vast amount of safety data available, the selective use of tamoxifen and raloxifene in male and female patients with MD is an attractive and realistic alternative to steroids," noted Dr. Lu. This together with the detailed analyses of potential side effects and benefits in male and female populations provide rationale for early clinical trials. Importantly, the beneficial effects of SERMs are expected to extend to other forms of MD, beyond the specific mouse model investigated here.

A new report finds that extremely obese people who have a band surgically strapped around their stomachs to restrict food intake not only lose weight but also suffer less from arthritic knee pain.

The pain, say the study leaders at NYU School of Medicine, proceeds from the deterioration and related inflammation in knee joints caused in part by the extra weight they bear. And while the pain relief seen with lap-band surgery applied to all patients with osteoarthritic knees, researchers found that it was most helpful in the youngest men and women who lost the most weight.

"Our study shows that extremely obese people seeking relief from their knee pain should consider lap-band surgery earlier because the benefits from it being successful -- although significant for all ages -- decrease with age," says study senior investigator and rheumatologist Jonathan Samuels, MD.

An associate professor in the Department of Medicine at NYU School of Medicine, Samuels says it is likely that knee joints and cartilage become so damaged after a certain point that there is little cushion left for weight loss to preserve. Along these lines, the research team found that people in their 40s reported nearly twice as much pain relief after lap-band as those who had the surgery in their 50s.

More than 130,000 Americans have had the procedure done since 2011, national statistics show. Although the operation is considered relatively safe, complications may include nausea, stomach ulcers, and infection.

The study authors say their findings are especially important because one in three American adults is now overweight. Studies also show that the number of Americans with osteoarthritis has more than doubled since World War II.

Published online in the journal Seminars in Arthritis and Rheumatism in February, the new analysis was based on the experiences of 120 patients at NYU Langone Health who underwent lap-band surgery between 2002 and 2015. All were surveyed about what they remembered about their knee pain immediately before surgery, a year after their procedure, and for as long as 14 years later.

The main purpose of the survey, researchers say, was to find out why some extremely obese people showed more knee-pain relief from lap-band surgery than others. Study participants had an average body mass index, or BMI, of 40, which equates to a 5 feet and 10 inches-tall man who weighs about 280 pounds, or a 5 foot 6 inches-tall woman who weighs 250 pounds.

According to the survey results, men and women in their 40s experienced postsurgical knee pain reductions after one year of between 50 percent and 60 percent; while those in their 50s, one year later, had pain reductions between 30 percent and 40 percent; and those in their 60s, had reductions between 20 percent and 30 percent. Pain relief persisted for a decade in all patients monitored.

Results also showed that BMI at the time of surgery did not influence whose knee pain went down the most. People with BMIs in the upper 40s were just as likely to report decreased knee pain as people with BMIs in the lower 40s if they lost proportionally the same amount of total body weight.

However, study participants who lost the most weight had the steepest reductions in knee pain. Dropping more than 13 points on the BMI scale -- a measure of kilograms per meter squared based on height -- halved their pain scores, assessed on a scale from one to 10, when compared to people who lost eight or fewer BMI points.

Although the investigators acknowledge that surveys that gather self-reported symptoms can be biased to a certain extent, the consistency of their findings over time adds to their credibility, the NYU team noted.

Men who take the medication finasteride get a prostate cancer prevention benefit that can last 16 years - twice as long as previously recorded, according to SWOG clinical trial analysis published in the Journal of the National Cancer Institute.

This finding was made possible by a new research strategy - linking Medicare claims data to clinical trial data, in this case from a landmark study run by SWOG, the federally funded cancer clinical trial network. The SWOG study, known as the Prostate Cancer Prevention Trial, or PCPT, set out to see whether finasteride, a drug used to treat symptoms of prostate enlargement as well as male pattern baldness, would prevent prostate cancer in men over the age of 55. The study enrolled 18,882 men from 1993-1997. It was stopped in 2003 when investigators learned that finasteride reduced prostate cancer risk by 25 percent when compared with a placebo. SWOG leader Ian Thompson, Jr., MD, of CHRISTUS Santa Rosa Hospital Health System, was the study chair of PCPT.

Joseph Unger, PhD, a SWOG biostatistician and health services researcher from Fred Hutchinson Cancer Research Center, has a track record of using new research methods to answer bigger, bolder questions about cancer prevention and treatment. Along with SWOG colleague Dr. Dawn Hershman, Unger has pioneered for a decade the use of secondary sources of data, such as Medicare claims, U.S. Census Bureau data, and public health statistics from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, to examine new hypotheses.

For this study, Unger wanted to know if the protective effects of finasteride lasted longer than seven years - the amount of follow-up evaluated in the PCPT. Answering this question would typically require reopening the old study, reconnecting with patients, and conducting extensive follow-up - an expensive and time-consuming proposition. But Unger took another tack, requesting and obtaining a data use agreement from the federal Centers for Medicare & Medicaid Services to access to records from Medicare, the health insurance program for people over 65.

Using patient information from the PCPT, Unger linked patients enrolled in the PCPT to their Medicare claims from 1999 through 2011. The team was surprised to find they were able to successfully link 75 percent of PCPT trial participants. Unger and colleagues at Fred Hutch created an algorithm to flag a prostate cancer diagnosis in the Medicare data, and examined the diagnoses over time. The team identified 3,244 PCPT participants who were later diagnosed with prostate cancer over a median follow-up of 16 years, and found that participants on the PCPT that took finasteride had a 21 percent decreased risk of getting prostate cancer, compared to those who took a placebo drug, over the course of those 16 years.

"These findings raise the intriguing possibility that seven years of finasteride can reduce prostate cancer diagnoses over a much longer period than was previously shown," Unger said. "It's a low-cost generic drug, with minimal side effects, that can have a benefit that lasts long after men stop taking it."

At the same time, Unger said, the SWOG study shows the value of using Medicare claims to extend follow-up for trial participants and answer new questions about cancer care and prevention. "These secondary data sources are emerging as a new paradigm for long-term follow up for cancer clinical trials," he said. "It's an exciting new avenue of research."

Researchers have identified a 'genetic fingerprint' associated with the most deadly strains of malaria parasites, making these unique DNA regions potential targets for vaccine development.

An international research team led by the University of Melbourne found a small group of proteins was associated with the most severe strains of malarial infections, which are often fatal in young children who have not yet had a chance to develop a strong immune response to the parasite.

"We know that the great burden of mortality for malaria is in children under five," said Dr Michael Duffy, senior author on the study, from the University of Melbourne School of BioSciences and Bio21 Institute.

"But why children are at such high risk of death by malaria, and why some children die while others survive, has frustrated clinicians and scientists for years," he said.

"To better understand this difference, we compared the parasites causing the most severe malaria to parasites that cause uncomplicated or mild disease, which can be resolved by the immune system."

University of Melbourne Dean of Science Karen Day led a team that developed a 'fingerprinting' technique to identify different strains of malaria. The technique uses the parasite's var genes as a unique identifier. These genes code for different versions of the protein PfEMP1, which are expressed on the surface of red blood cells infected by malaria.

Each parasite has 60 of these genes that are different to other parasites and each gene is a mosaic of parts that can be shuffled to create new genes. The parasite also shuffles through the genes it uses like a pack of cards, thus appearing like different strains able to hide from our immune system.

Dr Duffy and his colleagues used RNA sequencing to sample parasites isolated from the blood of 44 adults in a location in which malaria is endemic in the state of Papua, Indonesia. Twenty three of these people had severe malaria. The researchers then compared 4662 pieces of var genes that were being expressed in severe cases, against those expressed in mild cases.

"This is the first time anyone's taken the parasite genes that are expressed in the blood of patients and sequenced everything that's there. We then assembled these sequences to work out what's present and what's different between severe and uncomplicated cases," Dr Duffy said.

They showed that only 20 to 30 of the thousands of var genes were being expressed at a higher rate in patients with severe malaria than uncomplicated malaria. These 20-30 var gene pieces included many not previously investigated but also all of the proteins associated with severe malaria in India and Africa were also more highly expressed in the severe cases in Papua, suggesting that this small group of deadly proteins is highly conserved around the world, providing the promise of new targets for vaccine design.

The researchers are now looking to test children in malaria-endemic regions of Africa, the group by far the most at risk from malaria death, to see if the novel deadly proteins they found in Papua are also present there.

"We also want to look for serological responses - whether people have antibodies to these proteins in their blood" Dr Duffy said.

"Perhaps kids with severe infections are missing antibodies to these proteins, and those who don't get severe infections have them?"

A broadly effective malaria vaccine remains elusive despite the backing of the Bill and Melinda Gates Foundation and hundreds of millions of dollars in research funding.

Dr Duffy said that because malaria is so diverse, and each parasite is constantly changing its attack strategy, finding a valid target for a vaccine is hard.

"But now we are starting to understand that of the thousands of versions of the PfEMP1 protein that are out there, only a handful, maybe 20 or 30, are causing the most severe cases of malaria," he said.

"And, so, we might be able to target vaccines to just these severe versions.

"We won't eradicate malaria, but we may be able to protect children when they are most vulnerable to death or serious morbidity from malaria, and thus greatly reduce the burden of the disease."

The World Health Organization reported 429,000 malaria deaths in 2015, 70 per cent of those were children under the age of 5.

This research is published in PLOS Biology, and was conducted by an international team of researchers from the Universities of Melbourne and Oxford, the Walter and Eliza Hall Institute of Medical Research, the Eijkman Institute for Molecular Biology in Jakarta, Indonesia, the Timika Malaria Research Program, Papuan Health and Community Development Foundation, Indonesia, the Peter McCallum Cancer Centre and Charles Darwin University.

A new paper in Music Therapy Perspectives examines the importance of music therapy in military healthcare. There has been an increase in music therapy to treat combat-related injuries in recent years. With this growth in the use of the therapy, the authors of this article believe it’s important for practitioners to publish information about effective music therapy treatment models for use in military settings.

The Military Healthcare System is presented with significant challenges following recent conflicts. With advances in military medicine and technology, survival rates are higher and more service members leave combat with psychological injuries, including traumatic brain injury and posttraumatic stress disorder. Such injuries present complex difficulties for treatment because of overlapping symptoms due to multiple health conditions, stigma of receiving care in military culture, and treatment options available within the Military Health System.

Integrating creative arts therapies in military treatment can present challenges. To overcome such issues and ensure consistent, high quality treatment the authors believe it’s important for music therapists and military treatment facilities to share program models and intervention protocols. In addition, they argue that publications of program evaluation and patient outcome data are needed in order to further validate program models, expand implementation, and provide research evidence. The paper outlines the current program models at two facilities, the National Intrepid Center of Excellence at Walter Reed National Military Medical Center and the Intrepid Spirit Center at Fort Belvoir.

Research has shown that creative arts therapies improve patient outcomes for military patients. Blast injury often results in damage to white matter and connective tissue, and psychological trauma resulting in PTSD disrupts processes in multiple brain regions, heightening some systems and deactivating others. Studies suggest that music can impact multiple neural networks simultaneously and can assist with rebuilding connections between various regions of the brain. Studies also show that the brain releases dopamine while people listen to music. This promotes motivation, learning, and reward-seeking behavior. Thus, listening to music can create an enhanced learning environment and rebuild damaged neural connections.

“Music therapy is a dynamic treatment method for service members recovering from the invisible wounds of war,” said Hannah Bronson, one of the paper’s authors. “Building awareness of its benefits with this population can extend the power of music and its healing properties to many more men and women in uniform and their families.”

A sense of meaning and direction in life is associated with living longer and experiencing less disease, disability, and cognitive impairment.

Now, a new study co-authored by Boston University School of Public Health (BUSPH) researchers has found that the children of centenarians, who tend to have similar healthy aging patterns and long lives like their parents, are also much more likely than the general population to have a strong sense of purpose.

The study, the first to examine purpose of life (PIL) in centenarian offspring, was published in The Journals of Gerontology, Series B.

"Aging well is not only escaping or delaying disease," says co-author Paola Sebastiani, professor of biostatistics at BUSPH. "Feeling good about your life is important and should be considered an important aspect of healthy aging."

The researchers used data from the BU-based New England Centenarian Study (NECS), which has recruited almost 4,000 centenarians, and some of their siblings and children, since 1994. The researchers compared the children of centenarians, who averaged 82 years old, with three other groups: their spouses; their birth cohort, made up of people whose parents were born around the same time as the centenarians but lived on average only into their early 70s; and participants in the Health and Retirement Study (HRS), a nationally representative study of more than 30,000 individuals over the age of 50.

The researchers compared PIL in the four groups using the PIL scores from the Ryff Scales of Psychological Well-Being. The Ryff PIL scale uses statements such as, "I enjoy making plans for the future and working to make them a reality" and, "My daily activities often seem trivial and unimportant to me," with respondents using a six-point scale from "strongly disagree" to "strongly agree."

Defining high PIL as scoring in the top quartile of the participants with a score at or above 5.85 out of 6, the researchers found 30 percent of the centenarian offspring had high PIL, compared to 21 percent of their spouses and only 14 percent of the birth cohort of septuagenarian offspring. Comparing the centenarian offspring with the HRS participants, with a top quartile cutoff score of 5.43, 41 percent of the centenarian offspring had high PIL, compared to only 19 percent of the HRS participants.

Adjusting for age, sex, education, and marital status, the researchers found that children of centenarians had 1.92 times the odds of high PIL as their spouses, 2.64 times the odds as the birth cohort participants, and 2.93 times the odds as the HRS participants.

The authors noted individuals tend to partner with people who have similar physical and psychological traits, which may account for the smaller difference in scores between the children of centenarians and their spouses. The spouses were also younger than the centenarian offspring on average, and by definition were more likely to be married, both of which are associated with higher PIL, the authors wrote.

"Having goals and making plans to work toward them may keep you more engaged with activities and social relationships, and give you a greater incentive to maintain good health and function," says senior author Stacy Andersen, assistant professor at Boston University School of Medicine. "Alternatively, low PIL may be a signal of unhealthy aging."

Bottom Line: Young mice that received molecularly targeted therapies used to treat brain cancer in human patients sustained cognitive and behavioral deficits, but the deficits were largely reversible through environmental stimulation and physical exercise. The study suggests that pediatric brain cancer patients may experience similar side effects of molecularly targeted therapies, and may benefit from efforts to remediate any cognitive deficits.

Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research.

Author: Joseph Scafidi, DO, MS, a neonatal neurologist at Children's National Health System, in Washington, D.C.

Background: "We've made significant progress against many childhood cancers, largely because of new, highly effective drugs," Scafidi said. "Targeted therapies currently used to treat brain cancers work because they target specific pathways in the cancer. However, these pathways are critical to the development of the brain, and so we set out to evaluate the cellular and behavioral effects of these drugs on a normal, developing brain.

"Primary central nervous system tumors continue to be the leading type of solid tumors in the pediatric oncology population," Scafidi continued. He said targeted therapies such as gefitinib (Iressa), sunitinib malate (Sutent), and rapamycin (Sirolimus) are now used to treat brain tumors, and interest in prescribing this class of drugs is growing. However, most clinical trials and pre-clinical studies on the drugs have been conducted in adults, therefore, the effects on pediatric patients are not fully known.

How the Study Was Conducted and Results: In this study, Scafidi and colleagues injected mice with either gefitinib, sunitinib malate, rapamycin, or a vehicle substance. One group of mice received the vehicle or drug when they were between 12 and 17 days old (analogous to early childhood); another group received the vehicle or drug when they were 17 to 22 days old (analogous to adolescence); and in a separate set of experiments, mice received the vehicle or drug when they were between 12 and 14 weeks old (analogous to adulthood).

Researchers assessed the drugs' effects on oligodendrocytes, a type of cell, in the white matter of the brain. They found that the mice that received the drugs at the youngest ages had the most significant decrease in oligodendrocytes; the mice that received the drugs as adults did not have significant changes. The researchers also analyzed myelin protein expression and again found the most significant changes in the mice that received the drugs at the youngest ages.

The researchers also measured other types of cells and found no significant changes, suggesting that the moleculary targeted therapeutics specifically target oligodendrocytes, Scafidi said.

To examine whether the drugs had behavioral effects, the researchers put the mice through a series of tasks: inclined beam-walking, novel object recognition, and maze running. The mice treated at a younger age with any of these three drugs showed the highest degree of behavioral deficits. Mice treated in adulthood showed no difference in cognitive performance.

Finally, the researchers randomized the mice to either typical housing or an "enriched environment," which included a running wheel and assorted toys. Researchers found that after about two weeks of living in the enriched environment, mice performed significantly better on the beam-walking task and the object recognition task.

Author Comment: Scafidi said the mice's improved performance supports the idea that the brain is plastic, and that cognitive deficits that result from childhood brain cancer treatments may be reversible. He said many cancer centers, including his own, provide different forms of cognitive and physical therapy to patients, and if this research is confirmed in further studies, it may provide a basis for making such therapy a widespread clinical practice.

"The fact is, these drugs do have an effect on the developing brain. The good news is that these effects can be attenuated by exposure to a stimulating cognitive and physical environment," Scafidi said.

Amsterdam, March 20, 2018 - World meat consumption has increased during the last decades, and evidence is mounting that high consumption of red and mainly processed meat is unhealthy to humans and is related to chronic diseases such as cancer, type 2 diabetes, and cardiovascular disease. A new study published in the Journal of Hepatology adds non-alcoholic fatty liver disease (NAFLD) to the list.

"NAFLD is considered as the hepatic component of the metabolic syndrome, with insulin resistance and inflammation as key factors in its pathophysiology," explained lead investigator Prof. Shira Zelber-Sagi, RD, PhD, from the School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Israel. "Unhealthy Western lifestyle plays a major role in the development and progression of NAFLD, namely, lack of physical activity and high consumption of fructose and saturated fat. Our study looked at other common foods in the Western diet, namely red and processed meats, to determine whether they increase the risk for NAFLD."

In order to test the association of type of meat and cooking method with NAFLD and insulin resistance, investigators undertook a cross-sectional study among individuals 40-70 years old who underwent screening colonoscopy at the Department of Gastroenterology and Hepatology in the Tel Aviv Medical Center, and who agreed to participate in a metabolic and hepatic screening study between 2013 and 2015.

NAFLD and insulin resistance were evaluated by ultrasonography and homeostasis model assessment (HOMA). Meat type and cooking method were measured by food frequency and detailed meat consumption questionnaires. Unhealthy cooking methods were characterized as frying or grilling to a level of well done or very well done. These methods produce heterocyclic amines (HCAs), which are pro-inflammatory compounds, and their intake was also calculated.

After excluding some of the participants due to factors such as viral liver disease and alcohol abuse, close to 800 subjects were included in the main analysis, of whom a sub-sample of 357 subjects completed the meat questionnaire. NAFLD was diagnosed in 38.7 percent of participants and insulin resistance in 30.5 percent. The proportion of red and white meat intake was about one third and two thirds, respectively, which is similar to the typical diet of the Israeli population. High meat eaters were slightly younger, mainly male, had a higher body mass index (BMI), caloric intake, and a worse metabolic profile.

The results showed that high consumption of red and processed meat is independently associated with NAFLD and insulin resistance regardless of saturated fat and cholesterol intake and other risk factors such as BMI. In addition, individuals who consumed large quantities of meat cooked using unhealthy methods and those already diagnosed with NAFLD who consumed high HCAs had a higher chance of having insulin resistance.

Low carb diets are frequently recommended to prevent metabolic diseases. These low carb diets can be very rich in animal protein, especially meat. While meat contributes valuable nutrients that are beneficial to health, including protein, iron, zinc, and vitamin B12, the current study indicates that meat should be eaten in moderation and the type of meat and its preparation method should be wisely chosen.

Although the association between high red and processed meat consumption and NAFLD remains to be confirmed by prospective studies, Prof. Zelber-Sagi, recommends limiting red and processed meat consumption in preference for healthier "white meat," such as chicken or turkey, including fish in the diet, and steaming or boiling food instead of grilling or frying meat at a high temperature until it is very well done.

"NAFLD is primarily a lifestyle-oriented disease. With sound medical and nutritional guidance from their clinicians, patients are better informed and equipped to implement the lifestyle changes needed to help reverse this disease," remarked Prof. Zelber-Sagi.

BIRMINGHAM, Ala. - University of Alabama at Birmingham researchers have identified a therapeutic target to prevent or delay heart failure from pressure overload of the heart, and a potential biomarker for the same. They say their animal studies carry clinical and translational potential.

In a study published in the journal JACC: Basic to Translational Science, Sumanth Prabhu, M.D., and colleagues found that preventing the early infiltration of CCR2+ macrophages into the heart, after experimental pressure overload in a mouse model, significantly lessened the heart's enlargement and reduced pumping ability that leads to later heart failure. Thus, this infiltration is a required step in the path toward heart failure.

Macrophages are immune cells that engulf and remove damaged or dead cells in response to tissue injury or infection. They also may present antigens to other immune cell types.

The most common forms of pressure overload are aortic stenosis -- a narrowing of the aortic valve of the heart that forces the heart muscle to overwork -- and high blood pressure. Aortic stenosis affects about one in 50 people over 65 years of age.

The UAB researchers used two different methods to prevent early macrophage infiltration -- an inhibitor of the macrophage cell-surface CCR2 chemokine receptor, and an antibody that selectively removes CCR2+ macrophages. Migrating macrophages use the CCR2 receptor to home in on damaged tissues in the body that are releasing chemokines. Preventing early macrophage infiltration, Prabhu and colleagues say, may offer a therapeutic target in human disease.

Researchers had previously known that pressure-overload heart failure is associated with inflammation cause by activated T-cells. The present UAB study showed the link between infiltrating macrophages and the T-cell response during pressure overload of the heart.

Prabhu and colleagues found, one week after inducing pressure load, that the heart showed increased expression of three attractant chemokines that are able to bind to the CCR2 receptor on macrophages. They also found an increased number of monocytes with the cell-surface markers Ly6C and CCR2 circulating in the blood, and they saw an eightfold increase in CCR2+ macrophages infiltrating into the heart. Those macrophages are derived from the circulating monocytes.

The UAB researchers suggest that increased circulating monocytes might serve as an easily measurable biomarker that reflects cardiac tissue CCR2+ macrophage expansion. The circulating monocytes -- along with other clinical, imaging and biochemical biomarkers -- could guide patient selection for a prospective clinical trial to find out whether modulating CCR2 macrophages in humans with pressure-overload hypertrophy will delay or prevent later transition to heart failure.

In the JACC: Basic to Translational Science study, the Prabhu group found that blocking the infiltration of macrophages to the heart also suppressed infiltration of inflammatory T-cells into the heart and T-cell expansion in the lymph nodes that drain from the heart.

"Taken together, these data indicate that blood monocyte-derived macrophages infiltrating the heart early after pressure overload are indispensable for the sustained T-cell activation that underlies remodeling progression and the transition to heart failure," the researchers concluded.

People with tough-to-treat triple negative breast cancer, whose tumors also don't allow for double-strand DNA repair, fare better when treated with a common adjuvant breast cancer chemotherapy combination, according to results from a SWOG clinical trial.

Published in Annals of Oncology, the trial results show that a well-established drug combination - adjuvant doxorubicin and cyclophosphamide (AC) chemotherapy - works well in this patient population. The results also show the value of collecting and preserving cancer tumor tissue. Priyanka Sharma, MD, of University of Kansas Cancer Center, and her team used nearly 20-year-old tumor samples stored in SWOG's biospecimen bank to conduct their analysis.

"Banking tissue in cancer research is a smart investment," Sharma said. "Tissue collected for one research study can be used for others, creating value for patients, investigators, and for the public who funds our SWOG research."

Sharma is a associate professor of medicine and a breast cancer oncologist at University of Kansas Cancer Center, and the vice chair of the breast committee for SWOG, the cancer clinical trials group that is part of the National Cancer Institute's (NCI) publicly funded National Clinical Trials Network (NCTN). Sharma has spent over a decade conducting research to better understand triple negative breast cancer. It's a catch-all term for cancers that test negative for three common factors that fuel breast cancer growth: estrogen receptors, progesterone receptors, and the HER2 gene. Triple negative breast cancers tend to grow faster and spread more frequently, and many current therapies aren't effective in slowing or stopping their growth.

How can physicians better treat people diagnosed with triple negative breast cancer? This question drove Sharma and her team to launch their SWOG study. Emerging evidence shows that many breast cancer patients' tumors have what is known as homologous recombination deficiency (HRD). This means that their cells have trouble repairing double-strand DNA breaks - a deficiency that can contribute to cancer. To better understand the link between HRD and triple negative breast cancer, and to test a hunch that repair-inhibiting therapies like AC chemotherapy would be effective in treating it, Sharma wrote a proposal focused on HRD, which was approved by SWOG and NCI. This allowed Sharma's team to access the SWOG biospecimen bank and use tissue from S9313 trial.

The SWOG bank is a treasure trove for researchers, holding more than 800,000 tissue, blood, and other biological samples taken to conduct SWOG trials. Sharma and her team used tissue gathered for S9313, a trial assessing the effectiveness of AC chemotherapy in patients with high- and moderate-risk breast cancers. The S9313 study stopped enrolling patients in 1997, but tissue samples from those patients remained, preserved in blocks of paraffin wax.

Investigators isolated genomic DNA and RNA from 425 of these samples, and could determine HRD status in 379 of them - an 89 percent success rate. Of those 379 cases, the team found that 67 percent had positive HRD status. After reviewing treatment responses to AC chemotherapy recorded in the S9313 trial, the team found that positive HRD status was associated with better disease-free survival. Put another way, patients whose tumor could not efficiently repair DNA damage (induced by AC chemotherapy) were more likely to remain cancer-free 10 years after AC chemotherapy treatment.

"We learned three interesting things from this trial," Sharma said. "First, we showed that assays tested in our study worked well in very old tissue samples. We also learned that 25 percent of triple negative breast cancer patients harbored BRCA 1 or BRCA2 mutations and tumors in these patients were HRD positive. However, presence of HRD was not restricted to just patients with BRCA mutations, as among patients without BRCA mutations, 55 percent also demonstrated tumor HRD. Finally, and most importantly, we learned that 67 percent of triple negative breast cancer patients - a solid majority - respond well to a standard, backbone chemotherapy combination. So, while, AC chemo is an old treatment, for many, it's still a good one. HRD status is a biomarker that, when identified, can potentially help a physician best tailor a chemotherapy treatment for that particular triple negative breast cancer patient."

Two new biomarkers for a type of cancer in children called neuroblastoma have been identified in a study published in the journal Cancer Cell. The findings are expected to have immediate significance for disease prognosis, and eventually also for treatment.

"There is a need for new methods of treatment for high-risk patients, and that's where our research can lead to truly great benefits," says Chandrasekhar Kanduri, professor of medical biochemistry and cell biology at Sahlgrenska Academy, Sweden.

Neuroblastoma is the most common form of childhood cancer of the peripheral nervous system, the part of the system that is not the brain or spinal cord. The disease can occur in the chest, neck, abdomen and adrenal glands and also spread to the spinal column. Symptoms may be general aches, anemia and skeletal pains.

When the disease is detected, the children are 17 months old on average and rarely over five years old. Milder variants of neuroblastoma may heal on their own in some cases, while the aggressive cases are the most deadly form of childhood cancer. Treatment is successful in less than half of these cases.

Identification of high risk patients is crucial, and this is where the new findings come in. With the support of patient data from Sweden (59 cases) and Germany (498 cases), researchers have identified two new types of RNA molecules that control the stability of tumor proteins and that, along with an already known RNA molecule, form a trio that can indicate how serious the condition of an individual patient is.

What can be measured, immediately after a diagnosis is made, is the strength of the three RNA molecules' gene expression. With a stronger expression, there is less scope for a particular tumor-inducing protein to stabilize itself, and vice versa.

This also has to do with a tug of war between the identified RNA molecules (6p22 lncRNAs) and the specific protein (USP36) in which a reading of relative strength can contribute to a better disease prognosis. Researchers believe this points to a near-term application in health care.

Eventually epigenetic drugs, which alter gene expression, may also play an important role in treatment of the disease.

"Epigenetic drugs activate the RNA molecules in question and thereby forestall the tumor, and in this way it will be possible to go in and treat high-risk patients," Chandrasekhar Kanduri says. "Our findings pave the way for development of drugs in the field, and we have close collaboration with clinical researchers in both Sweden and Germany."

Copenhagen: Many wives of advanced prostate cancer sufferers feel that their lives are being undermined by their husband's illness, with nearly half reporting that their own health suffered. In addition a focus subgroup has revealed that many feel isolated and fearful, and worry about the role change in their lives as their husband's cancer advances. This study, developed with the wives of men with metastatic prostate cancer who were being treated with hormone therapy, is amongst the first carried out on how prostate cancer affects the partners of sufferers. It was presented yesterday at the EAU conference in Copenhagen.

Prostate cancer is the most common male cancer. Prostate cancer which metastisises to other parts of the body is often difficult or impossible to cure, and so is often treated with androgen deprivation therapy (ADT), which slows down the tumour growth. ADT shuts down production of the hormone testosterone, but that leads to fatigue, frailty, and loss of sexual drive. The effects of prostate cancer and its treatment have been extensively studied in men, but there is almost no work on how this affects their partners.

A team of Danish researchers from Herlev and Gentofte University Hospital, led by registered nurse Jeanne Avlastenok and Dr. Peter Østergren, have been working with the wives and partners of men who had been undergoing exercise therapy to maintain body strength and resilience during prostate cancer treatment. They questioned 56 women on how the cancers were affecting the lives of their husbands. Nearly half of these women (26 women, i.e. 46%) reported that their partner's health problem had affected their own health.

The researchers randomly selected 8 women for in-depth, focus-group style interviews - aimed at encouraging the women to express how they are being affected by their partner's illness.

"We worked with the women as a group, encouraging them to be open about what they felt in a supportive group environment", said Jeanne Avlastenok.

"Three of the women - those with early stage disease - were less burdened than the others, but the remaining five expressed some significant concerns.

Many felt increasingly socially isolated. Their husbands were fatigued both by the illness and by the treatment, which meant that they couldn't socialize as a couple, which made the women feel cut off from social support".

Sample Comment: ''Because he sleeps so much we do not visit the family or our friends and do not have many guests'' said one.

RN Jeanne Avlastenok continued, "They also gradually developed a real fear of being alone, even within the relationship. They felt that they had to be strong, which meant that they couldn't share the burden of the illness.

The last theme which worried the women was over the role change in their relationship. As their men became less able to fulfil their usual roles, the women had to undertake tasks which had previously fallen to the men. Many of these are simple tasks but for the women they represented a sea change in the way their lives were structured".

Sample Comment: 'We have 22 windows and my husband thinks that he still can polish them and also do all the gardening. But nothing happens and he doesn't want me to arrange professional help''

All of the women were worried that their husbands would develop significant pain as the disease progressed.

The team stresses that the focus group findings is very much qualitative work on a small sample. "But in any study, you need to do the qualitative work before moving to any larger sample", said Dr. Peter Østergren, "We needed to let the women express their concerns first, so we can understand which questions to ask

Commenting, Professor Hein van Poppel (Leuven, Belgium), EAU Adjunct Secretary General for Education, said:

"Many prostate cancer patients have a hard time, both physically and emotionally, and this work shows that this stress can spill over and affect wives and partners. This is good for neither of them. Good mental and emotional health needs to be part of how we judge a treatment, and we need to try to ensure that both patients and their partners get the support they both need".

Professor van Poppel was not involved in this research, this is an independent comment. Only departmental funds were used for this research.

CHICAGO--Children with obesity may be more impulsive than those with normal weight, but during family-based behavioral treatment (FBT), the more impulsive of children with obesity may lose more weight, a new study suggests. The results of the study will be presented in a poster on Sunday, March 18, at ENDO 2018, the 100th annual meeting of the Endocrine Society in Chicago, Ill.

FBT aims to change parent and child behaviors and is currently the recommended intervention for children with obesity.

"Our novel results indicate that impulsivity may be a risk factor for uncontrolled eating and excessive weight gain," said lead study author Christian L. Roth, M.D., professor of pediatrics at the Seattle Children's Research Institute in Washington. "Children who rated high in impulsivity had higher body mass index (BMI) measures and greater body fat mass compared to those who rated lower in impulsivity."

"However, we found that children with obesity who were rated as more impulsive prior to starting FBT had greater weight-loss success in the program compared to children with obesity who were rated as less impulsive," added co-author Kelley Scholz, MSW, research supervisor at Seattle Children's Research Institute.

At the beginning and end of their six-month FBT obesity intervention, the researchers tested 54 children with obesity and 22 healthy-weight children, all between 9 and 11 years of age. The authors rated the children for impulsivity using attention and inhibition tasks from the NEPSY-II (Developmental NEuroPSYchological Assessment) tests. The healthy-weight children did not take part in the FBT program but were tested at the beginning and end of the study along with the participants who had obesity.

At baseline, a larger proportion of children with obesity scored as high-impulsivity compared with healthy-weight children. Among children with obesity, those who scored high in impulsivity had higher BMI and greater fat mass.

The children with obesity and their families took part in 24 weekly FBT session that involved a meeting between the family and a staff member in a private room for about 30 minutes with discussion of issues specifically related to that family. Also, 45-minute parent and child group sessions were held in a large conference room.

The meetings focused on food, physical activity education and behavioral skills such as self-monitoring and environmental control, using praise and rewards to reinforce positive eating and physical activity.

The NEPSY-II inhibition test results predicted weight loss. Of the 40 children with obesity who completed the study, the 18 who were rated high-impulsivity had a greater drop in BMI than the lower-impulsivity obese children. Inhibition scores improved at the end of the FBT program, and the children whose inhibition scores improved most had greater drops in BMI and fat mass.

The researchers recommend further related research.

The National Institutes of Health supported this study.

The researchers will discuss the findings during a press conference Monday at 9 a.m. Central. Register to watch the news conference at endowebcasting.com.

The incidence of all cancers combined was similar for Métis men and significantly higher for Métis women compared to non-Aboriginal men and women, found a study published in CMAJ (Canadian Medical Association Journal)

Canada's Métis people are 1 of 3 groups officially named in the Canadian Constitution as the "aboriginal peoples of Canada", along with Inuit and First Nations peoples. Métis people, who are descendants of early unions between First Nations women and European fur traders, have unique culture, traditions and nationhood. Aboriginal peoples in Canada have higher rates of poverty and unemployment as well as obesity, tobacco smoking and unhealthy diet compared with non-Aboriginal Canadians.

There are more than 450 000 Métis in Canada (1.4% of the total population). However, there is a lack of national data on the incidence of cancer as well as cancer survival rates in this unique population.

In this large study, researchers linked data on self-reported Métis ancestry from the 1991 Canadian census to national cancer and mortality databases between 1992 and 2009. In the 11 050 Métis adults (aged 25 to 99 years), 1090 cancers were diagnosed over 185 000 person-years. Compared with non-Aboriginal adults in the study, Métis adults were significantly younger, were more likely to live in rural areas as well as Canada's Prairie provinces, and had lower educational and income levels.

The rates of cancer were similar for Métis and non-Aboriginal people for many types of cancer, although Métis adults had significantly higher rates for lung cancer in both sexes separately; for liver, larynx and gallbladder cancers in both sexes combined; and for female breast and cervical cancers. Survival rates for prostate cancer were poorer for Métis men compared with non-Aboriginal men with prostate cancer. Incidence rates were significantly lower for melanoma and leukemia in Métis adults and for colorectal cancer in Métis women, compared with non-Aboriginal people.

"The cancer burden of Métis people has been understudied in Canada, so this study substantially increases our knowledge of cancer risk and prognosis in this community," says Dr. Loraine Marrett, Scientist Emeritus, Cancer Care Ontario. "The evidence found in this study shows us that more action is needed to reduce the incidence of cancer, improve survival and provide better health outcomes for Métis people."

The study was conducted by researchers from Cancer Care Ontario, University of Toronto, Statistics Canada and Métis National Council. It was funded by a grant from the Canadian Institutes of Health Research.

"Cancer incidence and survival among Métis adults in Canada: results from the Canadian census follow-up cohort (1992-2009)" is published March 19, 2018.