Body

A Rutgers study has found a significant increase in head and neck cancers among workers and volunteers who responded to the 9/11 terrorist attacks on the World Trade Center (WTC), pointing to newly emerging risks that require ongoing monitoring and treatment of those who were exposed during the initial response.

The study, which is the first to report on head and neck cancers in WTC first responders, found a 40 percent increase in diagnosis of these diseases between 2009 and 2012.

The study appears in the International Journal of Cancer.

The findings highlight the need to examine the potentially carcinogenic effects of WTC exposure in the context of other strong risk factors and the need for continued medical monitoring of WTC responders, particularly the police and military.

"Since cancers are diseases of long latency, the findings of significant excess cancer in this period point to a newly emerging trend that requires ongoing monitoring and treatment of WTC-exposed persons," said lead author Judith Graber, an associate professor at Rutgers School of Public Health and a researcher at Rutgers Environmental and Occupational Health Sciences Institute.

The results were part of a two-year study funded by the U.S. Centers for Disease Control and Prevention examining whether first responders were at greater risk of human papillomavirus (HPV)--related throat and tongue cancer because of their exposure during recovery efforts in lower Manhattan.

The most prevalent increases were oropharyngeal cancers, which are often associated with HPV infection, and laryngeal cancer, but not oral and nasal cancers. The study also found that head and neck cancers were most associated with responders who were over 55, were non-Hispanic whites or who worked in military or protective service occupations and performed rescue and recovery and maintained the perimeter after the attacks.

The research began when clinicians treating WTC-exposed responders at Rutgers' World Trade Center Health Program became concerned about an usually high number of patients with cancers of the head and neck. They compared the incidence of head and neck cancers in 73 people among the program's 33,809 WTC responders from 2003 through 2012 to the number of expected cases based on the New Jersey State Cancer Registry.

"This excess occurrence in head and neck cancers is plausible since first responders inhaled debris clouds containing many known carcinogens," said Graber, who is also an associate member in the Cancer Prevention and Control Program at Rutgers Cancer Institute of New Jersey. "In addition, these carcinogenic exposures might add to or increase the effect of known personal risk factors for some head and neck cancers, such as tobacco smoking, heavy alcohol use and oral HPV infection."

The findings highlight the need to examine the potentially carcinogenic effects of WTC exposure in the context of other strong risk factors and the need for continued medical monitoring of WTC responders.

Ann Arbor, January 17, 2019 - According to a new study published in the American Journal of Preventive Medicine, nearly four in ten of all youth who died by suicide in 16 states between 2009 and 2013 were Medicaid enrollees.

"Almost 40 percent of youth who died by suicide were covered by Medicaid, suggesting effective suicide screening of enrollees could substantially decrease suicide mortality in the United States," explained lead investigator Cynthia A. Fontanella, PhD, Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

While the overall rate of suicide was consistent for Medicaid and non-Medicaid groups and the highest suicide rates in both groups were among older youth and males, there were notable differences in a few demographic subgroups. For example, there were significantly higher percentages of suicide among the Medicaid population of youth aged 10 to 14 years, females (regardless of age), and individuals who died by hanging. This is valuable information that can be used to better target screening and prevention efforts and help meet the National Action Alliance for Suicide Prevention's Research Prioritization Task Force (RPTF)'s goal of reducing suicide deaths and attempts by 20 percent by 2025.

The study analyzed data on the 4,045 youth, aged 10 to 18 years, who died by suicide between 2009 and 2013 in 16 states: California, Florida, Georgia, Illinois, Indiana, Massachusetts, Michigan, Minnesota, New York, North Carolina, Ohio, Oregon, Texas, Virginia, Washington, and Wisconsin. These states represent the ten most populous states in the US, span all regions of the country, and account for two thirds (65 percent) of the total child Medicaid population. Death certificate data were matched with Medicaid data and the Injury Statistics Query and Reporting System. Age-, gender-, and cause-specific mortality rates were calculated separately for both the Medicaid and non-Medicaid groups.

Suicide is the second leading cause of death among individuals aged 10-24 years. More teenagers die from suicide than from cancer, heart disease, AIDS, birth defects, stroke, pneumonia, influenza, and chronic lung disease combined. In pursuit of the National Action Alliance for Suicide Prevention's shared vision for a "nation free from the tragic experience of suicide," the RPTF released a research agenda aimed at reducing suicide deaths and attempts by 20 percent by 2025. To achieve this goal, they recommended that targeted interventions within "boundaried populations" (e.g., population defined by a service setting or organizational function) be an immediate research focus because of the ability to identify and reach large numbers of individuals with highly concentrated suicide risk within service system settings appropriate for intervention.

The Medicaid program is an especially important boundaried setting for youth suicide prevention efforts. In any given year more than 36 million children are enrolled in Medicaid and they experience more suicide risk factors, including mental illness, compared to the general population. Despite the broad reach of the program, no previous studies have examined suicide among youth enrolled in Medicaid. The few existing studies of suicide mortality within health systems have focused on adults served by the Veterans Health Administration, enrolled in one state's Medicaid program, or an HMO network.

"This is the first study to examine suicide mortality in a national sample of youth enrolled in Medicaid and to compare suicide rates between Medicaid and non-Medicaid populations. As knowledge about the risk and protective factors associated with suicide risk among youth advances, this study provides a previously unavailable comparison point for other health systems that may be initiating surveillance of suicide mortality in their populations," explained Dr. Fontanella. "Our findings, together with prior research indicating Medicaid subgroups experience more child maltreatment and poverty-related adversity than non-Medicaid youth, suggest a need to develop the capacity of healthcare delivery systems to implement trauma-informed approaches across the continuum of care."

(Boston)--A new study led by Boston University School of Public Health (BUSPH) researchers finds that states with higher levels of household gun ownership also have higher overall youth suicide rates, with every 10 percentage-point increase in household gun ownership associated with a 26.9 percent increase in the youth suicide rate.

Published in the American Journal of Preventive Medicine, the study is the first to examine the relationship between household gun ownership and youth suicide rates while controlling for differences in the rate of youth suicide attempts across states.

"The availability of firearms is contributing to an increase in the actual number of suicides, not just leading youth to substitute other means of suicide for guns," says BUSPH predoctoral fellow Anita Knopov, the study's lead author.

The researchers used data from the Centers for Disease Control and Prevention (CDC) on suicides by youth between the ages of 10 and 19 years old from 2005 to 2015. They also used state-level data from the Youth Risk Behavior Surveillance System (YRBSS) to control for rates of risk behaviors as well as other factors associated with suicide, such as race, family constellation, poverty, education, and urbanicity.

The researchers found the overall youth suicide rate from 2005 to 2015 ranged from a high of 15 youth suicides per 100,000 people in Alaska to a low of 3 per 100,000 people in New Jersey. In the 10 states with the highest youth suicide rates, the average household gun ownership was 52.5 percent, compared to a household gun ownership rate of 20 percent in the 10 states with the lowest youth suicide rates.

"This study demonstrates that the strongest single predictor of a state's youth suicide rate is the prevalence of household gun ownership in that state," says study co-author Michael Siegel, professor of community health sciences at BUSPH.

There are hundreds of metabolic disorders -- including phenylketonuria, tyrosinemia, maple syrup urine disease and homocystinuria. These disorders lead to congenital diseases that produce a critical enzyme deficiency that interferes with the body's metabolism. The pathologies and symptoms vary among the diseases, but all of them are usually fatal and have no known cure. Most metabolic disorders affect infants.

The majority of these diseases currently lack effective treatments and patients must maintain a strict diet, avoiding certain food items that contain substances their bodies cannot break down. Often the proposed solutions, such as bone marrow transplants, are extremely expensive and only partially effective.

A new Tel Aviv University study suggests that the role of yeast, the world's most basic eukaryotic unicellular organism, may pave the way for the development of novel, more effective therapies. The research was published in Nature Communications on January 8.

"The same yeast that serves as a basis for the bread we eat and the beer we drink now also serves as an instrumental model of metabolic disorders," says Dr. Dana Laor of TAU's George S. Wise Faculty of Life Sciences, the lead author of the study conducted in Prof. Ehud Gazit's TAU laboratory.

"Three Nobel Prizes have been awarded to scientists engaging in research related to yeast in the last decade, and it's no wonder. Yeast grows quickly; it's affordable; and it's easily manipulated as a simple unicellular organism," Dr. Laor explains. "Now we, too, have harnessed its properties to gain insight into this devastating group of diseases."

The research is based on previous studies conducted by Prof. Gazit and his colleagues that revealed the role of toxic metabolite accumulation in the pathology of metabolic disorders. "We have known for a while now that amyloids are linked to severe diseases of the central nervous system, such as Alzheimer's, Parkinson's and Huntington's," Prof. Gazit says. "Recent experiments conducted in our lab have shown that they characterize genetic metabolic disorders as well. In such disorders, the gene responsible for producing an enzyme, which modifies a particular metabolite, is impaired.

"As a result, large quantities of that metabolite accumulate in the body and cause serious damage," he continues. "While each condition is separately considered as 'rare,' these disorders constitute a major proportion of pediatric genetic diseases."

In the new study, Dr. Laor genetically manipulated yeast cells to produce a toxic accumulation of the metabolite adenine, devising the first in vivo yeast model of a congenital metabolic disease as a result. The innovative platform will allow scientists to screen thousands of drug-like small molecules to identify molecules that could lead to novel therapies, which can then be developed by Big Pharma.

"Our pioneering research may help identify the molecular mechanisms involved in these diseases and thereby help to develop suitable drugs," says Dr. Laor.

The researchers recently received an investment commitment from the Tel Aviv University Technology Innovation Momentum Fund, which invests in promising breakthrough technologies, to collaborate with the BLAVATNIK CENTER for Drug Discovery to establish an integrated drug discovery platform for metabolic disorders. The fund is run by Ramot, the Business Engagement Center of Tel Aviv University. The researchers also have a patent pending on their yeast model.

"If you can successfully connect the pieces of the puzzle, then you can understand the biology behind a disease," Dr. Laor concludes. "It is critically important to understand the pathways leading to the toxicity caused by metabolite accumulations in order to develop the appropriate therapy. In this case, the lives of thousands of children may be saved and their quality of life significantly improved."

Organ transplant rejection is a major problem in transplantation medicine. Suppressing the immune system to prevent organ rejection, however, opens the door to life-threatening infections. Researchers at the University of Basel's Biozentrum have now discovered a molecular approach preventing rejection of the transplanted graft while simultaneously maintaining the ability to fight against infections.

When someone is confronted with 'foreign' material, be it viruses, bacteria, fungi, but also donor organs following transplantation, immune cells called T cells come into action to inactivate and destroy the 'foreign' material. Prof. Jean Pieters' team at the Biozentrum of the University of Basel together with collaborating scientists have now described a way to selectively suppress the immune reaction of the body against the donor organ by modulating the protein coronin 1.

By blocking this protein in T cells, these immune cells do not attack the transplanted organ anymore. However, the T cells continue to keep viruses, bacteria and fungal infections in check. These findings could potentially provide new approaches for reducing graft rejection in the future.

Engineered T cells prevent organ rejection but still fight infections

Coronin 1 is a protein that regulates T cells, which are essential for detecting and destroying invaders of the body. These T cells also recognize a transplanted organ as foreign. In a mouse model, the team has now been able to relate these graft rejections by T cells to coronin 1.

"By removing coronin 1, we observed that the T cells not only massively suppressed the immune response to the transplanted organ but even actively prevented its rejection," says first author Rajesh Jayachandran. "At the same time, we were astonished that coronin 1-depleted T cells continue to fight infections."

Finding a tolerance pathway for organ transplantation

The lab of Jean Pieters originally defined coronin 1 as a host factor hijacked by pathogens to survive within immune cells. The new research shows that in T cells, coronin 1 modulates a signaling pathway that produces the so-called 'second messenger' molecule cAMP. In the absence of coronin 1, cAMP levels drastically increase in T cells, thereby making these cells tolerogenic to the transplanted organ.

However, the group found that when challenged with microbial infections, there is still a way to stimulate T cells to control infections, since microbes induce the expression of certain molecules that neutralize the cAMP-mediated suppression.

Immune defense manipulation for organ transplantation?

The new findings have now demonstrated a way of manipulating the body's immune response by selectively suppressing the immune response of the host. Whether these findings may result in the development of therapies to allow retention of transplanted organs while retaining the ability to fight infections remains a task for the future.

Poor cardiorespiratory fitness could increase your risk of a future heart attack, even if you have no symptoms of a lifestyle illness today, a new study has found.

"We found a strong link between higher fitness levels and a lower risk of heart attack and angina pectoris over the nine years following the measurements that were taken," says researcher Bjarne Nes, from the Norwegian University of Science and Technology's (NTNU) Cardiac Exercise Research Group (CERG).

The study results have been published in the European Heart Journal.

Half the risk

"Even among people who seem to be healthy, the top 25 per cent of the most fit individuals actually have only half as high a risk as the least fit 25 per cent," Nes says.

Between 2006 and 2008, CERG researchers measured the cardiorespiratory fitness of 4527 men and women who participated in the HUNT3 population-based health survey in Nord-Trøndelag. None of the subjects had cardiovascular disease, cancer or high blood pressure, and most were considered to be at low risk of cardiovascular disease for the next ten years.

Nevertheless, 147 of the participants experienced heart attacks or were diagnosed with angina pectoris by 2017. These diseases signal that the coronary arteries in the heart are narrowed or completely blocked.

The researchers analysed the participants in groups based on their level of fitness in relation to others of the same age and gender. The risk proved to decline steadily as patient fitness increased. The correlation between fitness and cardiovascular risk also held after adjusting for other factors that differed between the most and least fit participants.

Gold standard for exercise testing

One of the greatest strengths of the study is that the test used maximum oxygen uptake to measure participant fitness. Earlier studies that have linked fitness level to disease risk in healthy populations have largely been based on less precise calculations of fitness, or on self-reported physical activity information.

"Maximum oxygen uptake is the most precise measure of fitness," explains Bjarne Nes.

Our body uses oxygen to drive metabolic processes that create energy for the muscles. Maximum oxygen absorption is simply the maximum amount of oxygen the body is able to absorb during physical activity. Heart, blood vessel and muscle functioning are all important for oxygen uptake.

"We know that patients with low oxygen uptake are at increased risk of premature death and cardiovascular disease. Our study shows that poorer fitness is an independent risk factor for coronary artery disease, even among healthy women and men who are relatively fit," says Nes.

So how fit should you be?

The study suggests that even a small increase in fitness can significantly improve health. For each increase of 3.5 fitness points, the risk of heart attack or angina decreases by 15 per cent.

"Our results should encourage people to use training as preventive medicine. A few months of regular exercise that gets you out of breath can be an effective strategy for reducing the risk of cardiovascular disease," says the study's first author, Jon Magne Letnes. He is a medical doctor and doctoral candidate in CERG.

Even if you never get in such good shape that you can say you have optimal protection, the study shows that participants' risk was lower the more fit they were.

"There is apparently no upper limit for training when it comes to the beneficial effects for the heart," writes British Professor Sanjay Sharma in a commentary accompanying the NTNU study.

Sharma's positions include that of medical director of the London Marathon, and he is considered one of the world's foremost experts in sports and heart disease.

Not just about exercise habits

To measure maximum oxygen uptake accurately, you have to breathe into a mask while running on a treadmill, where the speed increases or the incline gets steeper every minute. As you work at higher and higher intensity, your body needs more and more oxygen. The test ends when you can't run anymore, or when measurements show that the oxygen uptake is no longer increasing even though the treadmill speed is.

But why does the fitness number mean so much for your future health?

Researchers use a treadmill and a special mask to measure a person's maximum oxygen uptake, which is considered an important measure of fitness. Photo: Geir Mogen/NTNUNTNU

"Fitness isn't just a measure of how much you've trained in your life, but it also tells you what kind of genes you have. Other factors like obesity may also affect fitness. So we measure a lot of the body's functions, and from other studies we know that both genes and physical activity play a role in how your heart and blood vessels function," says Letnes.

Test your fitness

We can't do much about our genes, but we can change our exercise habits. Letnes believes it may be useful for doctors to use fitness measurements when assessing their patients' health risks.

"Fitness testing can motivate patients to get into better shape over time, and it focuses on health promotion rather than on illness. Although it may be inconvenient and difficult to measure oxygen uptake at the doctor's office, some simple and relatively accurate calculators exist that can provide a good estimate of fitness and disease risk," he says.

CERG has developed just such a fitness calculator, which is currently recommended by US health authorities. More than six million people have found their fitness numbers with this fitness tool. The calculator is found at https://www.ntnu.edu/cerg/vo2max

Philadelphia, January 15, 2019 - A clot in the retinal vein can lead to severe and irreversible loss of vision. In a report in the American Journal of Pathology investigators utilize a newly developed model of central retinal vein occlusion (CRVO) in mice that mimics many of the clinical features of CRVO in humans to study the pathologic effects of retinal occlusion and demonstrate the retinoprotective effects of the peptide adrenomedullin (ADM) and its receptor activity-modifying protein RAMP2.

"CRVO is the second most common retinal vascular disease next to diabetic retinopathy. In recent years, intravitreal administration of anti-vascular endothelial growth factor (VEGF) agents has been used to treat CRVO by suppressing retinal vascular permeability. However, recurrence of macular swelling and decreasing drug effectiveness are limitations of this approach. Therefore, identification of other therapeutic agents that enhance vascular integrity is desirable. In this study, we proved that the ADM-RAMP2 system is one of the novel therapeutic targets for treatment of CRVO," explained Takayuki Shindo, MD, PhD, of the Department of Cardiovascular Research at Shinshu University Graduate School of Medicine, Matsumoto, Japan.

The CRVO model was generated by combining intraperitoneal injection of Rose Bengal, a photo-activator dye that enhances thrombus formation, with laser photocoagulation. The most prominent changes noted were retinal hemorrhage and venous dilatation with tortuosity. Measurements of retinal thickness revealed prominent edema early after CRVO was induced, followed by gradual atrophy.

There are several possible ways ADM works in CRVO. ADM was originally identified as a vasodilating peptide expected to improve blood flow in CRVO. ADM also exerts anti-coagulating effects, which may suppress the hypercoagulability in CRVO. The researchers showed that ADM suppresses inflammation and oxidative stress associated with CRVO, both of which promote endothelial injury. ADM also suppresses vascular hyperpermeability, which is the cause of retinal edema, and increases vascular reperfusion. Thus, endogenous ADM likely exerts protective effects against the retinal damage caused by CRVO.

Based on these findings, investigators propose that the retinoprotective effects of the ADM-RAMP2 system make it a novel therapeutic target for treatment of CRVO.

"As the biological functions of ADM are likely different from VEGF antibodies, co-administration of ADM and VEGF antibodies may be a choice in some diseases. It may also be used as secondary therapy when patients become resistant to VEGF antibodies," commented Dr. Shindo.

Retinal vein occlusion, which affects an estimated 16.4 million individuals worldwide, can occur as a complication of hypertension, diabetes, dyslipidemia, or aging. Hallmark features are capillary loss, hemorrhage, macular edema, inflammation, and vascular complications. CVRO can be ischemic or non-ischemic depending upon whether blood flow has been interrupted; the ischemic type is irreversible and resistant to treatment. Anti-VEGF agents have been used to treat CVRO, but their use is limited by troublesome side effects, temporary benefit, and high costs.

LA JOLLA, CALIF. - Jan. 14, 2019 - We all know we should eat fruits and vegetables to keep our own heart healthy. But now, scientists are learning that epigenetic changes, or molecular tags that modify our DNA, can cause your children--and even your grandchildren--to inherit the negative effects of your poor diet. However, the details behind this inheritance--and how to stop it--have been unclear.

Now, scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified an epigenetic marker and two genes that caused heart failure in the children and grandchildren of fruit flies with high-fat-diet-induced heart dysfunction. Reversing the epigenetic modification or over-expressing the two genes protected subsequent generations from the negative heart effects of their parents' diet. These findings help explain how obesity-related heart failure is inherited and uncover potential targets for treatment. The study was published in Nature Communications on January 14, 2019.

The obesity epidemic is causing rates of heart failure to rise. Currently, more than 6 million people in the United States are living with heart failure, a number predicted to rise to more than 8 million in 2030, according to the American Heart Association (AHA). The condition occurs when the heart isn't able to pump enough blood throughout the body and typically affects people over the age of 65.

"Scientists have hoped for many years to identify the genetic basis of obesity, but answers remained puzzling and elusive," says Rolf Bodmer, Ph.D., senior author of the paper and director and professor in the Development, Aging and Regeneration Program at SBP. "Our findings reveal an inheritance mechanism behind heart failure fueled by a high-fat diet. We also uncovered an epigenetic factor and genetic targets that could be explored to protect individuals from the effects of their parents' or grandparents' poor diet."

There is evidence in humans that diet during pregnancy can have lasting effects on children. Babies born following a Dutch famine during World War II had higher rates of obesity and coronary heart diseases. Mothers who are overweight or obese are more likely to have children who have diabetes or other health difficulties. However, studying the underlying genetic and molecular mechanisms that are responsible for these observations have been difficult, hindering scientists' ability to break the chain of inheritance.

Fruit flies offer an attractive alternative to study genetics. Eighty percent of genes that cause disease in humans are also found in the fly. Additionally, their tube-shaped heart consists of only 80 heart cells, called cardiomyocytes (in humans, this tube folds into the four chambers of our heart). Their similarity to humans, simplicity and short life cycle--a new generation is born every fifteen days--make fruit flies an excellent model for studying the genes that contribute to human heart health.

In the study, the scientists fed fruit flies a diet rich in coconut oil for five days. These flies became overweight and developed traits that mimic human lipotoxic heart disease--the accumulation of fat in heart cells--and lead to heart failure, including irregular heartbeat (arrhythmia) and weakened heart contractions. Their children and grandchildren also had heart dysfunction, even when fed a normal diet.

By comparing generations of flies born from parents who ate normal diets, the scientists identified an inherited epigenetic marker called trimethylated lysine 27 in histone 3 (H3K27me3). Reducing the level of this epigenetic mark throughout the fruit fly protected the two subsequent generations from heart dysfunction.

The researchers also identified two genes involved in metabolism that were "turned down" in the next two generations of flies, called bmm and PGC-1. Revving up the flies' metabolism by overexpressing these genes also protected the hearts of the children and grandchildren of flies that ate a fatty diet. This protection lasted even if the subsequent generation consumed coconut oil.

This study provides the proof-of-concept results the scientists need to embark on further explorations.

"Next, we want to determine how and when these genetic and epigenetic changes are inherited, and to what extent they arise from the mother or father," says Bodmer. "We want to study fruit fly development at all stages--from egg to embryo to adulthood--to determine what the inherited primary changes are and at which point these changes are implemented to cause metabolic imbalance and lipotoxic heart disease. The answers we gain may help us learn how to intervene and stop these changes from passing to the next generation."

Adds Maria Clara Guida, Ph.D., co-first author of the study and a postdoctoral researcher in the Bodmer lab, "We'd also like to better understand how these two puzzle pieces--inherited epigenetic and genetic changes--are linked. Epigenetic changes are broad and typically control multiple molecular pathways. Better understanding the gene networks that are turned on and off upon eating a high-fat diet and how these changes are orchestrated by epigenetic factors could help us find important therapeutic targets to treat obesity-related heart failure."

AUGUSTA, Ga. (Jan. 14, 2019) - Lingering inflammation in the colon is a known risk factor for colorectal cancer and now scientists report one way it resets the stage to enable this common and often deadly cancer.

Inflammation is supposed to be a short-term response to an infection or other irritant in the body that is essential to eliminating it. But when inflammation persists, it can contribute to a myriad of common conditions, from cancer to cardiovascular disease.

In their quest to determine just how chronic inflammation of our large intestines, or colon, enables cancer, a scientific team led by Dr. Kebin Liu at the Medical College of Georgia and Georgia Cancer Center at Augusta University has found it turns one more protective mechanism against us and silences another.

The pathway to cancer they delineated in the journal Cell Reports goes like this: The chronic inflammation of ulcerative colitis prompts high levels of myeloid-derived suppressor cells, or MDSCs, to accumulate in the colon. High levels of MDSCs, in turn, produce higher levels of IL-10, a cytokine known to suppress inflammation. But at this high level, the function of IL-10, like the environment in the colon, changes. IL-10 instead activates STAT3, a protein that works as a gene regulator, which in turn increases expression of two genes - DNMT1 and DNMT3b - in the colon. These genes alter the DNA of and ultimately silence a tumor suppressor called interferon regulator factor 8, or IRF8.

Liu notes that the pathway they found that ends with silencing IRF8, likely is not a factor for non-colitis associated colon cancer.

Next steps include finding ways to inhibit high expression of IL-10 in the colon.

"IL-10 has a dual function. It can either be promoting or interfering with an immune response," says Liu. "What we found here is IL-10 promotes colon cancer."

In a healthy state, IL-10 and IRF8 have no known interaction but both work in different ways to protect against invaders, says Liu, a cancer immunologist in the MCG Department of Biochemistry and Molecular Biology.

The scientists set out to look at whether and how the two are connected in a chronically inflamed colon and test the hypothesis that IRF8 functions as a colorectal cancer suppressor.

They created a mouse missing IRF8 in the epithelial cells that line the colon and found plenty of evidence to support their hypothesis. The mice were much more susceptible to chronic inflammation, had less normal cell death in this high-cell turnover area and got more tumors. They also found that in the face of chronic inflammation, IRF8 is silenced, and that in human cancer, IRF8 is downregulated compared to normal colon tissues.

Meanwhile, they showed that in this altered environment, MDSCs and the IL-10 they produce were at higher levels and so were the two genes that ultimately silence IRF8. They found the same shifts in human colon cancer.

Liu says it's likely the high levels and timing that transform the role of IL-10 from suppressor of inflammation to suppressor of IRF8.

Colorectal cancer is among the top five common cancers and causes of cancer death in men and women in the United States, according to the Centers for Disease Control and Prevention.

Interleukin 10, or IL-10, is a cytokine, or signal that influences the behavior of nearby cells. It's known to suppress chronic inflammation, including inflammation-driven colitis and colorectal cancer. It has even known to suppress other cells cancer might commandeer like regulatory T cells, or Tregs, which can suppress an antitumor response.

IRF8 is a transcription factor, which means it helps regulate the activity of genes, and it plays an important role in the differentiation of red blood cells. It's normally expressed by the epithelial cells that line the colon as a layer of protection against the food and drink we put in our mouths.

MDSCs, are at low levels in most healthy people, and are adept at helping protect us from invaders, producing immune cells like macrophages, as well as IL-10. Like inflammation, MDSCs should be on the scene and active just until the problem is eliminated. But when chronically stimulated, like in chronic inflammation and cancer, they work instead to suppress the immune system.

Colitis is when the colon's lining becomes chronically inflamed and its important barrier function gets compromised by the increased number of immune cells that have moved in, likely in response to the immune system inexplicably recognizing common things like food and commensal bacteria in the gut as invaders.

Colitis affects males and females alike, often surfaces in the 30s, and can run in families. Symptoms of colitis include loose and more urgent bowel movements, diarrhea, abdominal pain and blood in the stool, according to the Crohn's & Colitis Foundation. Patients may have a loss of appetite, weight and energy.

Fears over a drug that can be used to treat alcohol addiction are unfounded, according to its first ever systematic review, led by academics at The University of Manchester.

Though the study found no evidence of any serious side effects linked to Naltrexone, many doctors hold back from prescribing the drug, often citing liver toxicity as a reason.

The review of 89 placebo controlled randomized clinical trials of naltrexone is based on 11,194 participants published in BMC Medicine.

Lead author Dr Monica Bolton, who conducted the research as part of her Master's degree at Manchester said: "Though naltrexone is licensed for the treatment of alcohol addiction, it remains under-utilized.

"And that has devastating consequences for individuals, health and social services in the UK and around the world.

"As far as we know there is only one contraindication: painkilling opiates, such as codeine. These should not be taken with naltrexone, as it works by blocking opiates in the brain.

"Up to 58% of alcohol-dependent people in England want to reduce their drinking, and this drug could help them succeed.

"It is cost effective and could reduce deaths."

According to the Office of National Statistics there were 7,697 alcohol-specific deaths in the UK in 2017, or 12.2 deaths per 100,000 population.

The Department of Health estimates the NHS costs of alcohol related problems as £3.5 billion every year.

Dr Alex Hodkinson from The University of Manchester said: "Previous research shows that naltrexone is prescribed to less than 0.5% of those eligible.

"And only 11.7% of those diagnosed with more severe forms of alcohol dependence received relevant drug therapy in the 12 months following diagnosis.

"Like all drugs for alcohol addiction, the chaotic nature of being an addict means this drug is simply not prescribed as much as it should be.

"It's also a cultural issue: there is a reluctance to prescribe one drug to combat addiction in another substance.

"Our review also shows that fears over side-effects are unfounded."

Naltrexone is being investigated for a range of other conditions such as other addictions, gambling and other impulse control disorders.

Anecdotal evidence also suggests that at a very low dose, it may also be able to treat a range of immune-modulated conditions including Crohn's disease, HIV, multiple sclerosis, fibromyalgia and Chronic Fatigue Syndrome (ME/CFS).

In the UK, around 1,400 NHS prescriptions for LDN are issued per year while over 12,000 people have received a private prescription in the last 10 years.

However, Dr Bolton argues that more research is needed to understand if the drug is effective for these conditions.

She said: "As it is safe, cheap and long out of patent, naltrexone would seem an excellent candidate for repurposing for a whole range of conditions.

"That is why it is imperative to find ways to fund clinical trials to test if it might one day be possible to license it.

"The problem is, it is extremely difficult to repurpose existing drugs - and naltrexone is just one example of many wasted opportunities to treat people and save the NHS money."

COLUMBUS, Ohio - African-American women at high risk of breast cancer are less likely than white women to pursue potentially life-saving preventive care, and racial disparities in health care and elsewhere are to blame, new research suggests.

"African-American women faced additional burdens at every step along the risk-management journey," researchers from The Ohio State University wrote in a newly published study in the journal Ethnicity & Health.

The study included in-depth interviews with 50 women - 30 white, 20 black - deemed at high risk of breast cancer based on family history and other factors.

They found that high-risk black women were less likely than white women to have genetic testing, take medications to protect them against cancer and to have or consider having their breasts or ovaries removed as a preventive measure, disparities that have been seen in previous studies. For example, 67 percent of white study participants said they or a relevant family member had undergone genetic testing, while just 20 percent of black women reported a history of genetic testing.

This study broke new ground as the first to help explain the reasons behind the racial differences. It showed that black women were less aware of their options and at a disadvantage when it came to getting access to information about prevention. Only three of the black women in the study, or 15 percent, had seen a specialist for their breast health. Meanwhile, 70 percent of the white women had consulted with a provider with special training.

Lead author Tasleem Padamsee said she expected differences by race. After all, health disparities between blacks and whites are common in various cancers and in other diseases. But this was the first study to look at differences in proactive prevention decision-making, and to drill down beyond those differences in an effort to explain why high-risk black women might make different choices than white women with the same risk.

After analyzing the feedback they received from study interviews and comparing it with preventive actions taken (or not taken) by those women, the researchers found that African-American women on the whole experienced differences in three separate "layers of information" that contribute to their decisions about managing cancer risk.

Those layers include receiving specific information about preventive care options, including genetic testing and prophylactic treatment; general information about managing breast cancer risk; and basic perceptions of breast cancer risk and prevention.

"We wanted to understand what women's experiences are like, how they make choices, and what influences those choices," said Padamsee, an assistant professor of health services management and policy and a member of Ohio State's Comprehensive Cancer Center.

Interviews were wide-ranging and revealed trends, such as a higher likelihood that African-American participants were burdened with other health care concerns, both their own and their family members', Padamsee said. These trends could help inform care provided to women in the future, prompting providers to acknowledge and look for ways to clear obstacles to lowering breast-cancer risk for patients. That might mean helping a woman with care for an elderly family member or for her children, assisting with transportation or working to find a way to get her in to see a specialist, she said.

"These groups of women are not just making different choices. They're having different experiences," she said. "Preventing cancer and lowering risk of death from cancer requires that all high-risk women receive the information they need."

The results of the study reveal the nuances of racial inequalities in health - the ways that structural, social and interpersonal inequalities combine to influence patients' choices.

Disparities are deeply rooted in social factors including poverty, education and racism that contribute to health outcomes, Padamsee said, adding that those obstacles aren't insurmountable, but solutions are complex and slow-moving.

A more immediate response to these inequities could be a focus on educating health care providers about the importance of providing risk-management information to all patients and referring high-risk women for genetic testing and specialist care.

"All health care providers could be educated about the relevance of risk information and risk-management options for African-American women, and the current disparities in provision of this information across race," wrote Padamsee and her co-authors.

The disparities seen in this study might be even more profound in the general population, Padamsee said, noting that the women who were part of her research were actively engaged in health care and willing and able to participate in research.

A team at LSTM with their collaborators in Malawi and Denmark have provided, for the first time, evidence which links the ability of red blood cells infected with the malaria parasite to bind to the cells lining the blood vessels of the brain, with the clinical syndrome cerebral malaria.

Cerebral malaria is a life-threatening complication of infection with the parasite Plasmodium falciparum. This complication is characterised by the parasite infected red blood cells accumulating in the brain and occurs in 1-2% of the over 200 million reported cases of malaria.

First author on the paper, published recently in the journal EMBO Molecular Medicine, Dr Janet Storm, explained: "Very little is known about why this serious complication occurs in some children but not others. However, it is understood that infected red blood cells, presenting with a protein called P. falciparum erythrocyte membrane protein 1 (PfEMP1) on its surface bind to host cells lining the blood vessels in many organs, including the brain."

A property of the PfEMP1 protein is its variability, which results in changes in the ability of infected red blood cells to bind to host cells in the brain. This has been suggested as the reason we only see cerebral malaria in some infected individuals, and if the infected red blood cells do not bind in the brain cerebral malaria cannot occur.

In their lab in at MLW in Malawi, the team utilised a flow-based adhesion assays to study the binding of infected red blood cells from children with cerebral or uncomplicated malaria to cells derived from human brain blood vessels. The team also used molecular techniques to study the PfEMP1 expressed by the infected red blood cells.

Results showed that binding of infected red blood cells from patients with cerebral malaria to the brain-derived cells was higher than that seen from patients with uncomplicated malaria. This suggests that in most cases P. falciparum avoids targeting the brain and that cerebral malaria only occurs when red blood cells express a subset of PfEMP1 proteins with particular adhesion phenotypes which allow for efficient binding to the cerebral blood vessels. Knowing that binding in the brain is a key feature of cerebral malaria allows researchers to focus their attention on developing new interventions for severe disease based on the interaction between infected red blood cells and the host cells lining the blood vessels in the brain.

People who eat higher levels of dietary fibre and whole grains have lower rates of non-communicable diseases compared with people who eat lesser amounts, while links for low glycaemic load and low glycaemic index diets are less clear. Observational studies and clinical trials conducted over nearly 40 years reveal the health benefits of eating at least 25g to 29g or more of dietary fibre a day, according to a series of systematic reviews and meta-analyses published in The Lancet.

The results suggest a 15-30% decrease in all-cause and cardiovascular related mortality when comparing people who eat the highest amount of fibre to those who eat the least. Eating fibre-rich foods also reduced incidence of coronary heart disease, stroke, type 2 diabetes and colorectal cancer by 16-24%. Per 1,000 participants, the impact translates into 13 fewer deaths and six fewer cases of coronary heart disease.

In addition, a meta-analysis of clinical trials suggested that increasing fibre intakes was associated with lower bodyweight and cholesterol, compared with lower intakes.

The study was commissioned by the World Health Organization to inform the development of new recommendations for optimal daily fibre intake and to determine which types of carbohydrate provide the best protection against non-communicable diseases (NCDs) and weight gain.

Most people worldwide consume less than 20 g of dietary fibre per day. In 2015, the UK Scientific Advisory Committee on Nutrition recommended an increase in dietary fibre intake to 30 g per day [1], but only 9% of UK adults manage to reach this target. In the US, fibre intake among adults averages 15 g a day [2]. Rich sources of dietary fibre include whole grains, pulses, vegetables and fruit.

"Previous reviews and meta-analyses have usually examined a single indicator of carbohydrate quality and a limited number of diseases so it has not been possible to establish which foods to recommend for protecting against a range of conditions," says corresponding author Professor Jim Mann, the University of Otago, New Zealand.

"Our findings provide convincing evidence for nutrition guidelines to focus on increasing dietary fibre and on replacing refined grains with whole grains. This reduces incidence risk and mortality from a broad range of important diseases." [3]

The researchers included 185 observational studies containing data that relate to 135 million person years and 58 clinical trials involving 4,635 adult participants. They focused on premature deaths from and incidence of coronary heart disease, cardiovascular disease and stroke, as well as incidence of type 2 diabetes, colorectal cancer and cancers associated with obesity: breast, endometrial, oesophageal and prostate cancer. The authors only included studies with healthy participants, so the findings cannot be applied to people with existing chronic diseases.

For every 8g increase of dietary fibre eaten per day, total deaths and incidences of coronary heart disease, type 2 diabetes and colorectal cancer decreased by 5-27%. Protection against stroke, and breast cancer also increased. Consuming 25g to 29g each day was adequate but the data suggest that higher intakes of dietary fibre could provide even greater protection.

For every 15g increase of whole grains eaten per day, total deaths and incidences of coronary heart disease, type 2 diabetes and colorectal cancer decreased by 2-19%. Higher intakes of whole grains were associated with a 13-33% reduction in NCD risk - translating into 26 fewer deaths per 1,000 people from all-cause mortality and seven fewer cases of coronary heart disease per 1,000 people. The meta-analysis of clinical trials involving whole grains showed a reduction in bodyweight. Whole grains are high in dietary fibre, which could explain their beneficial effects.

The study also found that diets with a low glycaemic index and low glycaemic load provided limited support for protection against type 2 diabetes and stroke only. Foods with a low glycaemic index or low glycaemic load may also contain added sugars, saturated fats, and sodium. This may account for the links to health being less clear.

"The health benefits of fibre are supported by over 100 years of research into its chemistry, physical properties, physiology and effects on metabolism. Fibre-rich whole foods that require chewing and retain much of their structure in the gut increase satiety and help weight control and can favourably influence lipid and glucose levels. The breakdown of fibre in the large bowel by the resident bacteria has additional wide-ranging effects including protection from colorectal cancer." says Professor Jim Mann. [3]

While their study did not show any risks associated with dietary fibre, the authors note that high intakes might have ill-effects for people with low iron or mineral levels, for whom high levels of whole grains can further reduce iron levels. They also note that the study mainly relates to naturally-occurring fibre rich foods rather than synthetic and extracted fibre, such as powders, that can be added to foods.

Commenting on the implications and limitations of the study, Professor Gary Frost, Imperial College London, UK, says, "[The authors] report findings from both prospective cohort studies and randomised controlled trials in tandem. This method enables us to understand how altering the quality of carbohydrate intake in randomised controlled trials affects non-communicable disease risk factors and how these changes in diet quality align with disease incidence in prospective cohort studies. This alignment is seen beautifully for dietary fibre intake, in which observational studies reveal a reduction in all-cause and cardiovascular mortality, which is associated with a reduction in bodyweight, total cholesterol, LDL cholesterol, and systolic blood pressure reported in randomised controlled trials... There are some important considerations that arise from this Article. First, total carbohydrate intake was not considered in the systematic review and meta-analysis... Second, although the absence of association between glycaemic index and load with non-communicable disease and risk factors is consistent with another recent systematic review, caution is needed when interpreting these data, as the number of studies is small and findings are heterogeneous. Third, the absence of quantifiable and objective biomarkers for assessing carbohydrate intake means dietary research relies on self-reported intake, which is prone to error and misreporting. Improving the accuracy of dietary assessment is a priority area for nutrition research. The analyses presented by Reynolds and colleagues provides compelling evidence that dietary fibre and whole grain are major determinants of numerous health outcomes and should form part of public health policy."

WASHINGTON - Findings from a novel online questionnaire of people with chronic fatigue syndrome (CFS) who rated their perceptions of care in a hospital's emergency department suggest the majority of these patients do not receive proper care, say researchers from Georgetown University Medical Center.

The study, published in the journal Open Access Emergency Medicine, is the first known investigation of the presentation of CFS in the emergency department (ED). The findings highlight a profound lack of understanding of CFS by health care workers, says the study's senior investigator, allergist and immunologist James N. Baraniuk, MD, a professor of medicine at Georgetown who treats people with CFS.

He says two-thirds of respondents report they either would not go to an ED because they believed they wouldn't be taken seriously, or had previous unsatisfactory experiences. Only a third of patients in the survey said they received appropriate treatment in the ED.

"The high proportion of patients who were basically told 'It is all in your head' by ED staff indicates that there is much misunderstanding and misgivings about the diagnosis of CFS. These patients should feel they are respected and that they can receive thorough care when they feel sick enough to go to an ED," he says.

Baraniuk says more training is needed for ED staff and physicians to better understand the disorder.

The 282 participants in the survey all had physician-diagnosed CFS. Participants were predominantly women (87 percent), educated (70 percent had at least a college degree), and had a primary care physician (93 percent).

From the survey, researchers determined that:

Only 59 percent of CFS patients had gone to an ED. In this group, 42 percent were dismissed as having psychosomatic complaints.

33 percent had symptoms consistent with a condition known as orthostatic intolerance, which occurs when a person feels faint when standing or sitting upright because not enough blood is reaching the brain and heart. The symptoms only improve when a person lies down.

CFS patients who went to the ED collectively rated caregivers' knowledge about CFS at 3.6 on a 10-point scale.

41 percent of CFS respondents did not go to the ED when ill because they felt nothing could be done or they would not be taken seriously.

"An already-available CFS Symptom Severity Questionnaire can be used in the ED to assist with the diagnosis of CFS, and to differentiate exacerbations of CFS symptoms from medical emergencies such as heart attacks or infections," Baraniuk says.

The number one reason for going to the ED was orthostatic intolerance.

"This is of importance because it provides a starting point for diagnosis and treatment by ED physicians," Baraniuk says. "This condition is something that can be readily addressed by ED caregivers. There is a real need for physician education that will improve their efficiency in identifying and treating CFS and in distinguishing CFS symptoms from other diseases in the exam room."

"We found that intolerance of exercise and intolerance to alcohol consumption were common to those diagnosed with CFS so this may help distinguish CFS from other conditions," says study co-author Christian R. Timbol, MD, who worked with Baraniuk as a medical student before becoming an emergency medicine resident physician at Thomas Jefferson University Hospital in Philadelphia.

Chronic fatigue syndrome affects between 836,000 and 2.5 million Americans, according to a National Academy of Medicine review of over 9,000 articles covering 64 years of research.

This reviewers renamed the syndrome "Systemic Exertion Intolerance Disease" to emphasize the disability, post exertional malaise or exhaustion that follows mild exertion, cognitive dysfunction and orthostatic intolerance (blood pressure and heart rate changes that cause dizziness) that are the salient features of the illness.

OTTAWA, January 10, 2019 - A study published today in the journal Gut shows that women with inflammatory bowel disease (IBD) are at greater risk of developing a mental illness after giving birth compared to the overall population. Study authors found that more than one-fifth of pregnant women with IBD had a new-onset mental health diagnosis. For every 43 pregnancies, there is one extra case of mental illness in a woman with IBD, compared to other women. The study used healthcare data on women who gave birth between 2002 and 2014 in Ontario, Canada to analyze the frequency of a new mental illness diagnosis in these women during and up to one year after a pregnancy.

Inflammatory bowel disease, or IBD, are a group of chronic gastrointestinal disorders in which people have ulceration, inflammation, and bleeding of their gastrointestinal tract, and are at risk for complications in other parts of the body. The two main subtypes are Crohn's disease and ulcerative colitis. People with IBD have an elevated risk of mental illness, especially anxiety and depression, potentially related to the inflammation in the gut affecting their brain.

"There's increasing awareness about mental illness in women during pregnancy and postpartum," said Dr. Eric Benchimol, senior author on the paper, and Senior Scientist at the CHEO Research Institute, Core Scientist at ICES, Associate Professor of Pediatrics and Epidemiology at the University of Ottawa, and a Pediatric Gastroenterologist at the CHEO Inflammatory Bowel Disease Centre. "Because of the elevated risk of mental illness in people with IBD, we felt it was important to study if women with IBD were at greater risk of developing a new mental illness during pregnancy and after giving birth compared to the overall population. We found the risk to be elevated during the post-partum period for women with IBD, particularly in the first 90 days after birth. We did not find an elevated risk during pregnancy."

In the study population, pregnant women with IBD had an elevated risk of developing a new-onset mental illness postpartum when compared to women without IBD - 22.7 per cent compared to 20.4 per cent. The women with IBD were at increased risk of two out of the four mental illness diagnostic categories: mood disorders (such as anxiety and depression) and substance use disorders (such as opioid dependency). These women were primarily treated by doctors in the outpatient setting, and did not need to be hospitalized. There was no evidence of increased risk for psychotic disorders (such as schizophrenia or hallucinations). The risk appeared elevated in women with Crohn's disease, but not ulcerative colitis.

"This is a small but significantly increased risk of new-onset mental illness in women with IBD," says Dr. Simone Vigod, lead author of the study, Scientist at the Women's College Hospital Research Institute, Chief, Department of Psychiatry, Women's College Hospital, and Adjunct Scientist at ICES. "Women with IBD face increased health challenges during pregnancy and after giving birth, and it's not just physical challenges. We need to look at both the physical and mental health needs of women and ensure they are getting the best treatment and support."

"These findings are very important for both patients and healthcare providers in the IBD community," says Mina Mawani, President and CEO of Crohn's and Colitis Canada. "If a pregnant woman with IBD knows that there's an elevated risk of mental illness during the post-partum period, she should discuss this potential risk with her healthcare provider. It's important that healthcare providers are aware of this increased risk in women with IBD. Together, women and their healthcare providers can look for opportunities to prevent mental illness during pregnancy and after birth as well as identify and treat it earlier."