The Observatory

Jan. 21, 2016


Due to a printing error, several lines were left out of the Continuing Education article in the  January 2016 print issue of MLO. The last paragraph of page 10 should read as follows: Clearly, there is a pressing medical need for highly accurate detection of cervical cancer and high grade abnormal lesions, especially in developing countries where the use of standardized Pap tests is limited. This test must involve a low-cost, quick, disposable, cervical cancer screening system that is sufficiently inexpensive to be employed as a primary screen globally. Limited laboratory infrastructure and instrumentation should be required to quantitatively screen the cervical samples and provide analysis quickly without the need for expensive, trained personnel.20,21


Study shows high frequency of spontaneous mutation in Ebola virus. In late December, nearly two years after the epidemic began, the World Health Organization declared the African country of Guinea to be free of Ebola virus infections. But the race to find a cure and therapies to combat the disease is forging ahead as officials warn that inattention could lead to another epidemic.

Texas Biomedical Research Institute scientists had been working on therapies, diagnostics, and vaccines for years before the 2014 epidemic, and a recent study by Dr. Anthony Griffiths published in the Journal of Virology shows a promising mechanism for attacking the virus.

Essentially, Ebola virus has the potential to evolve rapidly, but the genetic changes result in viruses that are weakened or not viable. Due to the unprecedented numbers of individuals infected in the latest outbreak, researchers have learned that Ebola virus does evolve in humans. Therefore, a better understanding of the capacity of the virus to evolve could lead to better diagnostics and potential therapies.

To determine whether Ebola virus was sensitive to increasing mutation rate, Griffiths’ group tested a drug called ribavirin. Preliminary experiments with mice suggested ribavirin could be a potential therapy and did cause the desired effect of increasing the mutation frequency enough to make the virus non-viable. Further testing in monkeys showed ribavirin reduced production of infectious Ebola virus, but results were not strong enough to recommend ribavirin as a treatment protocol.


Cancer cells poised for growth when opportunity knocks. Researchers have identified a mechanism that allows cancer cells to respond and grow rapidly when levels of sugar in the blood rise. This may help to explain why people who develop conditions in which they have chronically high sugar levels in their blood, such as obesity, also have an increased risk of developing certain types of cancer. The findings were published in the journal eLife by Susumu Hirabayashi, who leads the Metabolism and Cell Growth group at the MRC Clinical Sciences Centre based at Imperial College London, and Ross Cagan of the Icahn School of Medicine at Mount Sinai, in New York.

People with obesity often have persistently high levels of glucose and insulin in the blood. Over time this fades to background noise and the body tunes out, or becomes “insulin resistant.” With the gate closed, glucose can’t be absorbed efficiently so it builds up in the blood, and this accumulation can ultimately lead to type 2 diabetes.

But not all cells tune out. In fact, Hirabayashi and colleagues have previously shown that tumor cells in the fruit fly Drosophila melanogaster actively tune in.

Hirabayashi found that in flies fed a high-sugar diet, the “normal” cells became insulin-resistant, but the tumor cells didn’t. The tumor cells actually became more sensitive to insulin because they turned on a metabolic switch that triggered them to produce extra receptors for insulin. With insulin binding to many more receptors than usual, more glucose channels opened up and the tumor cells became a “sink” for the glucose that had nowhere else to go in the insulin-resistant body of the fly.


Infertility treatments do not appear to contribute to developmental delays in children. Children conceived via infertility treatments are no more likely to have a developmental delay than children conceived without such treatments, according to a study by researchers at the National Institutes of Health, the New York State Department of Health, and other institutions. The findings, published online in JAMA Pediatrics, may help to allay longstanding concerns that conception after infertility treatment could affect the embryo at a sensitive stage and result in lifelong disability.

Study authors found no differences in developmental assessment scores of more than 1,800 children born to women who became pregnant after receiving infertility treatment and those of more than 4,000 children born to women who did not undergo such treatment.

When the researchers considered only children conceived through ART (assisted reproductive technology), they found that they were at increased risk for failing any one of five domains, with the greatest likelihood of failing the personal/social and problem-solving domains.

However, twins were more likely to fail a domain than were singletons (single-born). So, when the researchers compensated for the greater percentage of twins in the ART group than in the non-treatment group (34 percent vs. 19 percent), they found no significant difference between the ART group and the non-treatment group in failing any of the domains.

Similarly, the researchers found no significant differences in the percentage of singleton children in the two groups who were referred for evaluation by developmental specialists (21.2 percent vs. 20.7 percent). Of the children diagnosed with a disability at three-to-four years old, no significant difference was found between the treatment and non-treatment groups: 13 percent, compared to 18 percent.

Innovations in gestational diabetes testing may better assess risk. Susan Hammond, who serves as Global Reagents Manager for Randox Laboratories, UK, writes in with news of a development on testing for gestational diabetes:

“More and more women in the United States are waiting until they’re older to start having children. The number of births to women between the ages of 45 and 49 rose 14 percent in 2013 over 2012, according to the Centers for Disease Control and Prevention’s National Vital Statistics Report. With this comes a responsibility for clinicians and laboratories to better assess those at risk of gestational diabetes and to aid better control of the condition for those who already have it. Quick and precise detection of risk of gestational diabetes and associated complications by clinical labs will provide women with the autonomy to take control of their maternal health.

“Innovations in maternal health testing have meant that analysis such as adiponectin and enzymatic fructosamine are now available in automated biochemistry formats and with more accurate methodologies; allowing laboratories to assess gestational diabetes risk and evaluate control of the condition with ease, speed, and accuracy. Such analytes have historically been non-routine and not easily accessible for clinical laboratories, but now, with little adjustment within the laboratory, these can be added to the test menu, allowing for detailed patient testing profiles.

“Current innovations in the area of gestational diabetes testing will ultimately secure the health, both during and post-pregnancy, of both mother and baby.”

Autoimmune disease

Researchers find link between processed foods and autoimmune diseases. The convenience of processed foods may come with an even bigger price tag than previously known, says an international team of researchers. In findings published in Autoimmunity Reviews, researchers from Israel and Germany present evidence that processed foods weaken the intestine’s resistance to bacteria, toxins, and other hostile nutritional and non-nutritional elements, which in turn increases the likelihood of developing autoimmune diseases.

The research team examined the effects of processed food on the intestines, and on the development of autoimmune diseases—conditions in which the body attacks and damages its own tissues. More than 100 such diseases have been identified, including type 1 diabetes, celiac disease, lupus, multiple sclerosis, autoimmune hepatitis, and Crohn’s disease.

The researchers focused on the increase in the use of industrial food additives aimed at improving qualities such as taste, smell, texture, and shelf life, and found “a significant circumstantial connection between the increased use of processed foods and the increase in the incidence of autoimmune diseases.”

Many autoimmune diseases stem from damage to the functioning of the tight-junctions that protect the intestinal mucosa. When functioning normally, tight-junctions serve as a barrier against bacteria, toxins, allergens, and carcinogens, protecting the immune system from them. Damage to the tight-junctions (also known as “leaky gut”) leads to the development of autoimmune diseases.

The researchers found that at least seven common food additives weaken the tight-junctions: glucose (sugars), sodium (salt), fat solvents (emulsifiers), organic acids, gluten, microbial transglutaminase (a special enzyme that serves as food protein “glue”) and nanometric particles.

Infectious disease

Antibiotics pave way for C. difficile infections by killing beneficial bile acid-altering bacteria. New research finds that bile acids which are altered by bacteria normally living in the large intestine inhibit the growth of Clostridium difficile. The work sheds light on the ways in which some commonly used antibiotics can promote C. diff infections by killing off the bile acid-altering microbes.

C. diff exists in the environment as a dormant spore. To colonize the gut, C. diff spores need to germinate and become growing bacteria that produce toxins and damage the large intestine. Researchers know that the use of certain antibiotics lead to a higher risk of C. diff infections, particularly among hospital patients. Casey Theriot, PhD, of North Carolina State University, wanted to know exactly how C. diff spores were interacting with the microbiota, or natural bacterial environment, within the gut.

“We know that within a healthy gut environment, the growth of C. diff is inhibited,” Theriot says. “We wanted to learn more about the mechanisms behind that inhibitory effect.”

Bile acids are made from cholesterol and aid in the digestion and absorption of fats. They also control lipoprotein, glucose, drug, and energy metabolism. Primary bile acids are made in the liver and travel through the intestinal tract. In the large intestine, bacteria convert these to secondary bile acids. Theriot found many bile acids have an inhibitory effect on C. diff growth.

Researchers looked at the intestinal contents of mice before and after treatment with many different antibiotics. They identified 26 different primary and secondary bile acids and defined the concentrations of those acids before and after treatment. Then they added C. diff spores to the contents in order to find out how the bacterium may germinate and grow in an actual gut environment.

Interestingly, the primary bile acids in the small intestine allowed spores to germinate, or begin to grow, regardless of the antibiotic treatment. But when the spores reached the large intestine, where normal gut bacteria generate secondary bile acids, those secondary bile acids stopped the C. diff from growing. When those bacteria—and the secondary bile acids—were not present following antibiotic treatment, the C. diff was able to quickly grow.


A microfluidic biochip for blood cell counts at the point of care. The blood cell count is among the most ubiquitous diagnostic tests utilized in primary healthcare. The “gold standard” that is routinely used in hospitals and testing laboratories is a hematology analyzer, which is large and expensive equipment and requires trained technicians and physical sample transportation. It slows turnaround time, limits throughput in hospitals, and limits accessibility in resource-limited settings.

Now, researchers from the University of Illinois at Urbana-Champaign, led by Rashid Bashir, PhD, have demonstrated a biosensor capable of counting blood cells electrically using only a drop of blood. Bashir’s team has developed a biosensor to count red blood cell, platelet, and white blood cell counts, and its three-part differential at the point of care, while using only 11 microL of blood.

The microfluidic device can electrically count the different types of blood cells based on their size and membrane properties. To count leukocyte and its differentials, red blood cells are selectively lysed and the remaining white blood cells are individually counted. Specific cells, like neutrophils, are counted using multi-frequency analysis, which probes the membrane properties of the cells. For red blood cells and platelets, one microL of whole blood is diluted with peripheral blood smear on-chip and the cells are counted electrically. The total time for measurement is under 20 minutes.

“Our biosensor exhibits the potential to improve patient care in a spectrum of settings, including resource-limited settings where laboratory tests are often inaccessible due to cost, poor prevalence of laboratory facilities, and the difficulty of follow-up upon receiving results that take days to process,” says Bashir.

“There exists a huge potential to translate our biosensor commercially for blood cell counts applications,” says lead study author Umer Hassan, PhD. “The translation of our technology will result in minimal to no experience being required for operation of the device. In addition, patients can perform the test at home and share the results with their primary care physicians via electronic means.”