Epigenetic changes present at birth – in genes related to addiction and aggression – could be linked to conduct problems in children, according to a new study by King’s College London and the University of Bristol.
Conduct problems (CP) such as fighting, lying and stealing are the most common reason for child treatment referral in the UK, costing an estimated £22 billion per year. Children who develop conduct problems before the age of 10 (known as early-onset CP) are at a much higher risk for severe and chronic antisocial behaviour across the lifespan, resulting in further social costs related to crime, welfare dependence and health-care needs.
Genetic factors are known to strongly influence conduct problems, explaining between 50-80 per cent of the differences between children who develop problems and those who do not. However, little is known about how genetic factors interact with environmental influences – especially during foetal development – to increase the risk for later conduct problems. Understanding changes in DNA methylation, an epigenetic process that regulates how genes are ‘switched on and off’, could aid the development of more effective approaches to preventing later conduct problems.
The study used data from Bristol’s Avon Longitudinal Study of Parents and Children (ALSPAC) to examine associations between DNA methylation at birth and conduct problems from the ages of four to 13.
The researchers also measured the influence of environmental factors previously linked to early onset of conduct problems, including maternal diet, smoking, alcohol use and exposure to stressful life events.
They found that at birth, epigenetic changes in seven sites across children’s DNA differentiated those who went on to develop early-onset versus those who did not. Some of these epigenetic differences were associated with prenatal exposures, such as smoking and alcohol use during pregnancy.
One of the genes which showed the most significant epigenetic changes, called MGLL, is known to play a role in reward, addiction and pain perception. This is notable as previous research suggests conduct problems are often accompanied by substance abuse, and there is also evidence indicating that some people who engage in antisocial lifestyles show higher pain tolerance. The researchers also found smaller differences in a number of genes previously associated with aggression and antisocial behaviour, including MAOA.
Dr Edward Barker, senior author from King’s College London, said: ‘We know that children with early-onset conduct problems are much more likely to engage in antisocial behaviour as adults, so this is clearly a very important group to look at from a societal point of view.
‘There is good evidence that exposure to maternal smoking and alcohol is associated with developmental problems in children, yet we don’t know how increased risk for conduct problems occurs. These results suggest that epigenetic changes taking place in the womb are a good place to start.’

King’s College London
www.kcl.ac.uk/ioppn/news/records/2017/06-June/Epigenetic-changes-at-birth-could-explain-later-behaviour-problems.aspx

A new diagnostic developed by Alberta scientists will allow men to bypass painful biopsies to test for aggressive prostate cancer. The test incorporates a unique nanotechnology platform to make the diagnostic using only a single drop of blood, and is significantly more accurate than current screening methods.
The Extracellular Vesicle Fingerprint Predictive Score (EV-FPS) test uses machine learning to combine information from millions of cancer cell nanoparticles in the blood to recognize the unique fingerprint of aggressive prostate cancer. The diagnostic, developed by members of the Alberta Prostate Cancer Research Initiative (APCaRI), was evaluated in a group of 377 Albertan men who were referred to their urologist with suspected prostate cancer. It was found that EV-FPS correctly identified men with aggressive prostate cancer 40 percent more accurately than the most common test—Prostate-Specific Antigen (PSA) blood test—in wide use today.
"Higher sensitivity means that our test will miss fewer aggressive cancers," said John Lewis, the Alberta Cancer Foundation’s Frank and Carla Sojonky Chair of Prostate Cancer Research at the University of Alberta. "For this kind of test you want the sensitivity to be as high as possible because you don’t want to miss a single cancer that should be treated."
According to the team, current tests such as the PSA and digital rectal exam (DRE) often lead to unneeded biopsies. Lewis says more than 50 per cent of men who undergo biopsy do not have prostate cancer, yet suffer the pain and side effects of the procedure such as infection or sepsis. Less than 20 per cent of men who receive a prostate biopsy are diagnosed with the aggressive form of prostate cancer that could most benefit from treatment.
It’s estimated that successful implementation of the EV-FPS test could eventually eliminate up to 600-thousand unnecessary biopsies, 24-thousand hospitalizations and up to 50 per cent of unnecessary treatments for prostate cancer each year in North America alone. Beyond cost savings to the health care system, the researchers say the diagnostic test will have a dramatic impact on the health care experience and quality of life for men and their families.

Medicalexpress
medicalxpress.com/news/2017-06-blood-nanotechnology-aggressive-prostate-cancer.html

Tens of thousands of cancer patients each year may benefit from an immunotherapy regimen called PD-1 blockade, based on results from a new clinical study. The findings establish genetic markers that help physicians identify which patients might respond to the therapy, which had been approved previously for a select few classes of cancer.
"What we describe in this paper applies to about 4% of patients with advanced cancer, regardless of the tumour type," said Bert Vogelstein of Johns Hopkins University, a senior author on the paper.
In an 86-patient clinical trial encompassing 12 different kinds of cancers, Dung Le and colleagues at Johns Hopkins University demonstrated that the immunotherapy drug pembrolizumab (an anti-PD-1 antibody) was effective against multiple types of tumours. All of the patients had cancers with defects in a genome maintenance pathway called mismatch repair (MMR).
"One patient, a young graduate student, was scheduled to go into hospice for terminal care two days prior to receiving the test result that showed he had an MMR-deficient tumour," said Vogelstein. "Shortly after beginning treatment, he went into remission. Since then he’s been able to finish his Ph.D., get married and live a happy and productive life."
PD-1 blockade doesn’t directly destroy tumours, but instead aids the immune system in targeting cancer cells — which can suppress the body’s defences in order to thrive.
Until recently, PD-1 blockade therapies were approved for only a select few classes of cancers, such as melanoma and lung cancer. Yet in a historic May 2017 decision , the United States Food and Drug Administration ruled that tumour genetics, rather than tissue of origin, could be used as a clinical indicator for pembrolizumab therapy.
"This is the first approval for a treatment that is tissue agnostic, which means clinicians can use pembrolizumab for any tumour with mismatch repair deficiency," said Le.
As many as 60,000 cancers every year might harbour MMR mutations that would render them susceptible to PD-1 blockade, according to Le and colleagues’ analysis of genome sequencing data from 12,019 cancers representing 32 distinct tumor types.
PD-1 blockade takes advantage of the fact that MMR defects make cancer genomes inherently unstable, giving them a potential Achilles’ heel.
"Tumours that have more chaotic genomes produce more proteins that are recognized by the immune system," said Geoff Lindeman, a breast cancer researcher at Walter and Eliza Hall Institute of Medical Research, who was not involved in the study.
Different types of cancers experience various levels of genomic chaos. Most tumors harbor roughly 50 genetic alterations whereas skin and lung cancers tend to have mutation counts well in the hundreds, arising from exposure to environmental DNA-damaging agents like UV light or cigarette smoke. Problems with MMR can push tumors towards thousands of mutations per cell.
Yet even with such high mutational loads, cancer can still escape from the immune system.
"Tumors find ways to switch off the immune cells," said Vogelstein. "Checkpoint inhibitors like anti-PD-1 can re-awaken these immune cells for an extra weapon in the ongoing war between cancer and the immune system."
Though the trial is still ongoing, 11 patients were able to stop taking the therapy; they have remained disease-free with no evidence of recurrence for an average of 8.3 months.

AAAS
www.aaas.org/news/studies-open-possibility-immunotherapy-more-cancer-patients

The European Patent Office has announced Dutch product manager Jan van den Boogaart (57) and Austrian researcher Prof. Dr. Oliver Hayden (45) as finalists for the 2017 Inventor Award in the “Industry” category. The two Siemens Healthineers employees have invented an automated method for detecting the life-threatening disease malaria. On the basis of their own research, they jointly developed a method for the Siemens Healthineers Advia 2120i hematology systembased on a combination of parameters that define whether a patient has  malaria. With this method, the Advia 2120i hematology system can run malaria tests automatically as part of a full blood panel. The great advantage is the high throughput at lower cost than with other methods, such as microscopic examination.
Until now, the most reliable method has been a microscopic examination of the blood for plasmodia, which calls for experienced, trained personnel, as recognizing plasmodia under the microscope is not easy. The process is also very time-consuming. In recent years, malaria has also been diagnosed more and more with fast tests: a test strip that detects parasite-specific antigens. But if used improperly, that test is unreliable, and it’s also expensive. www.siemens.com/press/PR2017040278HCENwww.epo.org/news-issues/press.html

Dr Benjamin Tang and his team have developed a world first test to identify which influenza patients will need urgent, life-saving, medical treatment.
The High-risk Influenza Screen Test (HIST) measures ‘an early warning signal’ released by the patient’s body into their blood to ‘kick start’ their immune system’s fight against the infection.
The test needs only a single drop of blood and a few hours to predict, with 91 percent accuracy, which influenza patients will develop potentially deadly secondary infections, such as pneumonia.
Previously doctors could only test for influenza infection but didn’t know which patients would be at risk of rapid deterioration.
“Influenza can sometimes kill otherwise healthy people in the prime of their lives,” says Dr Tang.
“By using the High-risk Influenza Screen Test we’re eavesdropping on the immune system to pick up when the body first mounts a defence against a serious, life-threatening, infection.
“The early warning means we have a greater chance to treat the patient’s infection before it overwhelms them and potentially kills them,” Dr Tang said.
The research deciphered the genetic codes that immune cells release to warn the body of a serious infection, such as pneumonia, caused by the influenza virus.
HIST will be particularly useful during pandemics when there is a delay in developing vaccines for strains of the influenza virus.
“We can now test people during a pandemic, or outbreak of a new flu virus, to identify those who might be at greater risk of developing serious complications.
“The test works with any flu infection as it looks at how the body reacts rather than the strain or type of virus.”
Dr Tang said HIST could also be used to track the effectiveness of new drugs in clinical trials by accurately plotting the patient’s immune response.
The patented High-risk Influenza Screen Test runs on equipment already available in most pathology laboratories.

The Westmead institute
www.westmeadinstitute.org.au/news-and-events/2017/new-flu-test-one-drop-of-blood-could-save-your-li