News
Rapid identification of life-threatening bacteria in hospitals
A new, easy-to-adapt and inexpensive analytical procedure has been developed by researchers from the Institute of Physical Chemistry of the Polish Academy of Sciences. The procedure identifies bacterial species responsible for an infection developing in a patient. The main role is played by innovative bioconjugates - luminescent, magnetic microparticles coated with specific bacteriophages. The detection device is a flow cytometer. In the cytometer the sample is passed through a nozzle from which the stream that flows is so narrow that all the larger particles in the solution, particularly cells, have to flow one by one. The stream is lit by lasers and surrounded by detectors that record the light reflected from individual particles, scattered to the sides and emitted by them.
The researchers combined microspheres with bacteriophages using a compound from the carbodiimide group known as EDC (this substance is used by many chemists to bind together different particles). Images obtained with confocal microscopy confirmed that the new bioconjugates usually two or three bacteriophages adhered to each microparticle. From this, the world's first bioconjugates with triple functions were obtained: binding only to one species of bacteria, responsive to the magnetic field and capable of glowing (fluorescent).
Bioconjugates with one type of bacteriophage detect only one species of bacteria. However, due to the ease of preparation of bioconjugates, interested hospital laboratories could, on their own and without any major problems, prepare a dozen or even several dozen types of potentially useful bioconjugates, each of them with bacteriophages infecting different species of bacteria.
Two infants treated with universal immune cells have their cancer vanish
Doctors in London say they have cured two babies of leukemia in the world’s first attempt to treat cancer with genetically engineered immune cells from a donor. The experiments, which took place at Great Ormond Street Hospital, raise the possibility of off-the-shelf cellular therapy using inexpensive supplies of universal cells that could be dripped into patients' veins on a moment’s notice. The British infants, ages 11 and 16 months, each had leukemia and had undergone previous treatments that failed, according to a description of their cases published in Science Translational Medicine.
In the off-the-shelf approach, blood is collected from a donor and then turned into "hundreds" of doses that can then be stored frozen, says Julianne Smith, vice president of CAR-T development for Cellectis, which specializes in supplying universal cells. "We estimate the cost to manufacture a dose would be about $4,000," she says. That’s compared to a cost of around $50,000 to alter a patient’s cells and return them. Although the cases drew wide media attention in Britain, some researchers said that because the London team also gave the children standard chemotherapy, they failed to show the cell treatment actually cured the kids. "There is a hint of efficacy but no proof," says Dr. Stephan Grupp, director of cancer immunotherapy at the Children’s Hospital of Philadelphia, who collaborates with Novartis. "It would be great if it works, but that just hasn’t been shown yet."
Hematology
Study published in the American Journal of Clinical Pathology highlights rapid detection of platelet function using T2MR® technology
T2 Biosystems, Inc. has published a new study in the American Journal of Clinical Pathology. The study supports the use of T2 Magnetic Resonance (T2MR®) technology as a platform with the potential to provide a more sensitive and biologically relevant read-out of platelet dysfunction than traditional diagnostic methodologies, including Light Transmission Aggregometry (LTA). "Among those advantages, we saw that T2MR detected platelet function at similar or lower platelet counts than LTA. In addition, it appeared to be more sensitive to residual platelet function than LTA. Further, smaller blood volumes were required, little to no sample preparation was needed and turnaround time to result was faster," said John McDonough, chief executive officer at T2 Biosystems.
LTA remains the mainstay method for the measurement of platelet function in diagnosing patients with qualitative platelet disorders and suspected platelet function disorders, despite being labor-intensive, being available only in specialized laboratories and requiring particular technical expertise. Additionally, because LTA does not involve activation of coagulation, it assesses the relationship between platelets and fibrinogen rather than the more physiologically relevant relationship between platelets and fibrin. T2MR is a novel platform that measures hemostasis in whole blood, requires small blood volumes, is technically simple and yields results in minutes.
Transfusion Medicine
How 1,000 new genetic variants were discovered in blood groups
The international project 1,000 Genomes is so far the world's largest mapping of human genetic variants. By creating a new computer program, Mattias Möller processed the genomes of 2,504 people. He imported these genomes to his newly developed database Erythrogene, and matched them against previously known genetic variants. The result was the discovery of 1,000 hitherto unknown mutations which could have a negative effect in the case of blood transfusions, for example. Mattias Möller's study showed that 89% of the genetic variants were previously known, but the study found the remaining unknown 11%. This discovery from Lund University in Sweden was published recently in the journal Blood Advances.
"Never before has there been a worldwide mapping of blood group genes in healthy individuals. Most previously known blood group variants were discovered when a blood transfusion failed, i.e. when it didn't work between the donor and the recipient. I started from the genes instead, to find variations in DNA which might give rise to a new antigen, likely to cause problems in case of transfusion, for example," explains Mattias Möller, doctoral student at the Department of Laboratory Medicine. "The new online database enables researchers to study a specific blood group and see where in the world it occurs."
Microbiology
New drug reduces risk of 'superbug' re-infection by 40%
C. difficile sickened almost half a million Americans in 2011, according to the most recent numbers from the U.S. Centers for Disease Control and Prevention (CDC). A newly approved drug may help in the battle against the superbug. In two clinical trials, researchers found that the drug, called bezlotoxumab, marketed as Zinplava, cut the risk of a recurrent C. difficile infection by almost 40%. That's important, because the gut infection commonly comes back after treatment with antibiotics approximately around 20% of the time, according to the U.S. Centers for Disease Control and Prevention (CDC).
The studies involved over 2,600 adults who all received antibiotics for a first-time or recurrent C. difficile infection. Some were randomly assigned to receive a Zinplava infusion, while the rest received a saline infusion that served as a placebo. Over 12 weeks, 16-17% of Zinplava patients suffered a recurrent infection. That compared with 26%-28% of placebo patients, the findings showed. The drug's main side effects included fever, nausea and diarrhea, which affected between 5-7% of patients. Dr. Mark Wilcox, a professor of medical microbiology at the University of Leeds, agreed that doctors will have to give the drug based on patients' personal odds of a recurrence. According to Wilcox, some high-risk patients include those who are age 65 or older, have a compromised immune system or have a severe C. difficile infection. "Bezlotoxumab was more effective in such patients," said Wilcox. "So doctors should consider adding it to standard-of-care antibiotics according to these risk factors."
Related Article: Antibiotic Overuse Behind 'Superbug' Outbreak in U.K. Hospitals
Blood test may predict who lives or dies with ebola
While the 2014-16 Africa Ebola outbreak taught physicians and scientists much about virus, many questions remain. Foremost among them: why do some people survive an infection, while others die? A team of researchers led by Boston University and other international agencies has discovered a biomarker that can help predict the progression of the disease: a handful of genes that are over-activated in patients who succumb to the disease. These genes indicate an overly aggressive primary immune response, which can damage organs—particularly the liver and paradoxically, may hamper a more targeted immune response.
Published in the journal Genome Biology, the research suggests a new type of blood test that while still in the preliminary stages of development, might be useful in future outbreaks to steer patients to the best treatment. When the researchers looked for biomarkers in blood samples, they found the test would correctly predict who survived or succumbed to the disease 70% of the time based on the biomarkers. Evidence was also found for activation in genes that make albumin and fibrinogen, indicators of severe liver damage. "Because the liver produces many critical molecules for the body, including proteins that allow blood to clot", says Connor, "the liver’s demise may be what gives the virus the upper hand in some patients."
Molecular Genetics
TCGA study identifies genomic features of cervical cancer
Cervical cancer accounts for more than 500,000 new cases of cancer and more than 250,000 deaths each year worldwide. The vast majority of cases of cervical cancer are caused by persistent infection with oncogenic types of HPV. Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified novel genomic and molecular characteristics of cervical cancer that will aid in the subclassification of the disease and may help target therapies that are most appropriate for each patient.
In the new study, a comprehensive analysis of the genomes of 178 primary cervical cancers, the researchers found that nearly three-quarters of cervical cancers had genomic alterations in either one or both of the PI3K/MAPK and TGF-beta signaling pathways, which may also provide targets for therapy. An aspect of the study that is of particular interest was the identification of a unique set of eight cervical cancers that showed molecular similarities to endometrial cancers. These endometrial-like cancers were mainly HPV-negative, and they all had high frequencies of mutations in the KRAS, ARID1A, and PTEN genes. The authors noted that an important question raised by this study is whether HPV-positive and HPV-negative tumors will respond differently to targeted therapies. The study included authors from the National Cancer Institute and the National Human Genome Research Institute, both parts of the National Institutes of Health.
Research
Genital herpes vaccine shows promise in animal trials
Approximately 500 million people around the world are infected with the genital herpes virus, the researchers said in background notes. In the United States alone, an estimated one in six people aged 15 to 49 has genital herpes. A new vaccine for genital herpes could be nearing human clinical trials, researchers say. The vaccine has proven effective in animals against herpes simplex virus 2, the sexually transmitted virus that causes genital herpes, according to a new report. The new "trivalent" vaccine targets three different parts of the virus, shutting down its ability to enter cells and to evade detection by the immune system, said Dr. Harvey Friedman, professor with the University of Pennsylvania School of Medicine's Institute for Immunology.
In lab studies, the vaccine proved 98% effective in protecting guinea pigs against genital herpes infection, Friedman and his colleagues reported. The vaccine also promoted an immune response in monkeys, increasing the levels of antibodies targeting the virus, the study authors said. The study results were published in the journal PLOS Pathogens. It was pointed out that incorporating two different attacks into a single vaccine is a "novel strategy" that may revolutionize the field. "It may be a new era of vaccines," Friedman added. "This could open up the field to other viruses that are using evasion strategies that are different, but the same concepts could be applied."
Related article: Flawed herpes testing leads to many false positives — and needless suffering
How to Grow Human Organs in a Pig
Reports have emerged that researchers at the Salk Institute have, for the first time, successfully created human/pig chimera embryos. It was only recently that Juan Carlos Izpisúa Belmonte, the scientist leading the effort, wrote an article describing his dream of using chimeric animals to grow human organs for patients needing transplants.
While the idea of a human/pig chimera may conjure ghastly images of freakish-looking hog-people, the reality is much less disturbing. In fact, one of the most notable successes of the experiment, according to Belmonte, was that the contribution of the human cells to the developing pig embryo was very small. The fear, from an ethical standpoint, had been that the human cells would over-contribute, straying from the target site to the developing brain, for example. This did not happen, and the human cells survived the full four months during which the embryos were allowed to develop. The researchers encountered many challenges throughout the study, making clear that despite the relative success of this experiment, creating a whole, mature human organ in an animal remains a distant prospect. Nonetheless, the work continues.
Click to see the graphic that breaks down how researchers hope the process will one day work
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