The Observatory

May 24, 2015

News

Researchers suggest possibility of serum, genomic tests to identify aggressive criminals. As people worldwide tried to come to grips with the fact that co-pilot Andreas Lubitz intentionally crashed a Germanwings airliner into the French Alps, killing all 149 passengers and crew, psychologists sought to make an important clarification: Early news reports had stressed that Lubitz apparently struggled with depression; he probably did, but an act of this nature cannot be explained by clinical depression alone, but rather by sociopathic aggression. Lubitz's mental life may have been more like that of a terrorist, or a mass murderer who uses more conventional methods to kill, than a depressed individual.

Jeff Victoroff, MD, of the Keck School of Medicine, University of Southern California, told the Los Angeles Times, “We need to stop talking as if this was a suicidal guy with access to an airplane. This was a murderous guy who probably had elements of a mood disorder and personality disorders.”

The Times article, “Aggression, not just depression, led copilot to crash plane, experts say” (April 5), also explores a fascinating possibility: that future tragedies of this sort might be headed off through laboratory studies of individuals who display behavior that suggests they may pose this kind of threat. Studies have already linked low levels of serotonin and the hormone oxytocin to aggressive (also suicidal) behavior. Perhaps even more intriguingly, the results of genetic studies may have relevance. One Finnish study identified a variation on the genome that was found three times more often in violent, repeat criminals than in the general population. Can the study of biomarkers prevent future Andreas Lubitzes from threatening innocent lives?

Cancer

New analysis of breast cancer subtypes could lead to better risk stratification. For the first time, researchers have used national data to determine the incidence of the four major molecular subtypes of breast cancer by age, race/ethnicity, poverty level, and several other factors. The four subtypes respond differently to treatment and have different survival rates. The new data will help researchers more accurately stratify breast cancer by clinically relevant degrees of risk and potentially have an impact on breast cancer treatment. The findings were reported in the Journal of the National Cancer Institute.

Breast cancer subtypes have major implications for determining treatment, and they may hold important clues to the origins of breast cancer. There are four molecular subtypes, which can be approximated by their hormone receptor (HR) status and expression of the HER2 gene: Luminal A (HR+/HER2-), Luminal B (HR+/HER2+), HER2-enriched (HR-/HER2+), and triple negative (HR-/HER2-). These subtypes are now being recorded by cancer registries across the nation, giving statisticians the ability for the first time to comprehensively examine breast cancer rates based on clinically meaningful subtypes.

The new report suggests that some of the differences in rates of breast cancer incidence and mortality across racial and ethnic groups are related to differences in the incidence of different subtypes. Geographic variation in rates that the authors observed were based on multiple factors, including underlying demographic patterns, regional cultures and associated behaviors, as well as access to care.

Diabetes

Australian researchers develop saliva-based glucose test. Researchers at the University of Newcastle in Australia have developed a saliva-based glucose test using a 2D printer, which could spell the end of needles and blood tests for people with diabetes. The test, which detects concentrations of glucose and is up to 100 times more sensitive than current blood sensors, integrates bio-sensors or chemical signatures into printed transistors.

Professor Paul Dastoor and his team at the University's Centre of Organic Electronics focus on the development of new electronic devices at the intersection between semi-conductors and plastics. The team has now turned its attention to diabetes.

“Because we have developed paint with semi-conducting particles, we can now 'download' electronic designs, print them relatively cheaply from an inkjet printer and, in principle, build any electronic device,” Dastoor says. “On this principle, we have developed a saliva-based test of glucose levels for diabetic patients using a reel-to-reel printer. We print electrical components using an ink that is a semi-conductor, mixing in the enzyme which will detect the presence and level of glucose when a person with diabetes places a sample of his or her saliva on the test.”

Genetics/Genomics

New target identified in fight against Alzheimer's, multiple sclerosis. Highlighting a potential target in the treatment of multiple sclerosis (MS) and Alzheimer's disease, new research suggests that triggering a protein found on the surface of brain cells may help slow the progression of these and other neurological diseases.

Working with mice, two research teams at Washington University School of Medicine in St. Louis independently linked the protein to the ability to clear debris from the brain. Such waste builds up both as a byproduct of daily mental activities and as a result of misdirected immune system attacks on brain cells. If too much debris is present in the brain for too long, it can contribute to neurological disease.

In one study, appearing online in Cell, scientists showed that Alzheimer's brain plaques build up more slowly in mice that have a defective version of the TREM2 protein. In another, published in Acta Neuropathologica, researchers showed that mice lacking the same protein had trouble cleaning up debris in the brain produced by damage to a protective coating on nerve cells. The problem is thought to occur in MS and other neurological disorders.

New autism-causing genetic variant identified. Using a novel approach that homes in on rare families severely affected by autism, a Johns Hopkins-led team of researchers has identified a new genetic cause of the disease. The rare genetic variant offers important insights into the root causes of autism, the researchers say. And, they suggest, their unconventional method can be used to identify other genetic causes of autism and other complex genetic conditions. A report on the study appears in the journal Nature.”

In genetics, we all believe that you have to sequence endlessly before you can find anything,” says Aravinda Chakravarti, PhD, a professor in the Johns Hopkins University School of Medicine. “I think whom you sequence is as important—if not more so—than how many people are sequenced.”

With that idea, Chakravarti and his collaborators identified families in which more than one female has autism spectrum disorder. For reasons that are not understood, girls are far less likely than boys to have autism, but when girls do have the condition, their symptoms tend to be severe. Chakravarti reasoned that females with autism, particularly those with a close female relative who is also affected, must carry very potent genetic variants for the disease, and he wanted to find out what those were.

The research team compared the gene sequences of autistic members of 13 such families to the gene sequences of people from a public database. They found four potential culprit genes and focused on one, CTNND2, because it fell in a region of the genome known to be associated with another intellectual disability. When they studied the gene's effects in zebrafish, mice, and cadaveric human brains, the research group found that the protein it makes affects how many other genes are regulated. The CTNND2 protein was found at far higher levels in fetal brains than in adult brains or other tissues, Chakravarti says, so it likely plays a key role in brain development.

Drugs of Abuse

Rate of opioid misuse is around 25 percent, addiction rate 10 percent, study reports. New estimates suggest that 20 percent to 30 percent of opioid analgesic drugs prescribed for chronic pain are misused, while the rate of opioid addiction is approximately 10 percent, reports a study in the April issue of the journal PAIN.”

On average, misuse was documented in approximately one out of four or five patients and addiction in approximately one out of ten or eleven patients” who were prescribed opioids as part of their treatment for chronic pain, write Kevin E. Vowles, PhD, University of New Mexico, Albuquerque, and colleagues. The researchers note extremely wide variation in reported rates of misuse, abuse, and addiction and raise questions about the benefits of widespread opioid use for chronic pain, given the harmful consequences.

Dr. Vowles and coauthors reviewed published studies to produce “updated and expanded” estimates of rates of problem opioid use. Prescribing of these powerful pain-relieving drugs has skyrocketed in the past 15 years. This sharp increase has coincided with an increase in opioid-related problems such as dependence, withdrawal, and overdose. Estimates were calculated using data from 38 reports, with adjustments for study sample size, quality, and methods.

Three specific types of problem opioid use were recorded: misuse, abuse, and addiction. On adjusted analysis, the average rate of opioid misuse was estimated at 21 percent to 29 percent. Misuse was defined as using opioids contrary to instructions, regardless of harmful or adverse effects. Adjusted average rates of opioid addiction—defined as continued opioid use with actual or potential harmful effects—ranged from eight percent to 12 percent.

Pregnancy/Prenatal

Body clock genes could hold key to recurrent miscarriages. Researchers at the University of Warwick in Coventry, England, and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust have discovered how body clock genes could affect women's ability to have children. The study pinpoints how body clock genes are temporarily switched off in the lining of the womb to allow an embryo to implant. The timing of this event is critical for pregnancy.

The researchers examined endometrial cells from womb linings of healthy women, and also biopsies from women who had suffered from recurrent pregnancy loss. The study found that women with recurrent miscarriages may be less able to regulate clock genes in the lining of the womb. Published in the Journal of the Federation of American Societies for Experimental Biology, the study also provides new insights into how night and shift work could affect female fertility.

It is hoped that by identifying the causes behind recurrent miscarriages, fertility experts will be able to help more prospective parents than ever before. The research could have major implications for in-vitro fertilization (IVF), as the findings suggest that fertility specialists could, in the future, target biorhythms in the womb to improve the environment for implanted embryos.

Researcher Jan Brosens, PhD, says, “It's crucial during pregnancy that mothers and their babies' embryos are able to synchronize. If this fails to happen, it can cause miscarriage. It can also increase the risk of complications in later stages of pregnancy such as pre-eclampsia, fetal growth restriction, and pre-term birth.”

Industry News

Biocept enters clinical collaboration with University of California, San Diego Moores Cancer Center. Biocept, Inc., a molecular oncology diagnostics company specializing in biomarker analysis of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), has entered into a clinical collaboration with University of California, San Diego Moores Cancer Center to determine the clinical utility of detecting biomarkers present in CTCs and ctDNA in blood samples for non-small cell lung cancer patients using Biocept's OncoCEE LU platform and CEE-Selector technology.

San Diego-based Biocept offers a quantitative blood-based method for the detection and monitoring of cancer mutations, which can help inform treatment decisions based on genomic information. The company is engaged in clinical study collaborations designed to demonstrate the utility of its liquid biopsy diagnostics to detect biomarker status in cancer patients, and for the assessment of tumor treatment response over time.

NYU College of Dentistry partners with Rheonix to develop test to detect HIV antibodies and RNA at point of care. New York University College of Dentistry has received a sub-award in the amount of $335,000 from a Small Business Innovation Research (SBIR) Phase II grant from the National Institutes of Health (NIH) to complete the development of a fully automated self-confirming assay that can simultaneously detect HIV/AIDS antibodies and viral RNA from the AIDS virus in one specimen. The $1.5M Phase II grant was awarded to Rheonix, Inc., an Ithaca, NY-based medical technology company that specializes in making automated and highly customizable molecular diagnostic devices.

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