News
Beaver’s genome mapped out to help celebrate Canada’s 150th birthday
Scientists have a gift for Canada as the country celebrates its 150th — and as a birthday present, it’s certainly unique. A team of molecular geneticists at Toronto’s Hospital for Sick Children has sequenced the genome of the Canadian beaver, Castor Canadensis, to mark the country’s sesquicentennial. The genome was sequenced using DNA from Ward, a 10-year-old male beaver that lives at the Toronto Zoo with its mate June — a nod to the Cleaver parents in the 1950s TV show "Leave it to Beaver." Their results were reported in the journal G3: Genes/Genomes/Genetics.
Si Lok, senior project manager at the centre and a co-author of the beaver genome paper, said the Sick Kids team maps about 10,000 human genomes a year, comparing them to reference examples that already exist. "But in the case of Ward, this is completely different," Lok said. "This is what we call ‘de novo’ sequencing, which literally means ‘from scratch.’ We actually don’t know what the beaver genome looks like, so we had to assemble it without knowing what the final picture of the jigsaw puzzle is. If we can do this, we can use the same technology and the same approach to identify new mutations in a human genome that we currently are missing."
Stephen Scherer, director of the hospital’s Centre for Applied Genomics, said the new approach will be used to better map genomes of families affected by autism to determine which, if any, mutated genes are behind the neurological condition in their children. In previous studies of other family groups, his lab has found that about 20% of autism cases are caused by genetic mutations.
Video: Watch this video from Sick Kids on the beaver’s genome sequencing.
Quality
Quality control materials: The classic make or buy decision
Regulatory entities and good laboratory practices require evaluating an assay’s performance characteristics before using it to test patient samples. Laboratories monitor the performance of the test using a quality control (QC) plan that alert of problems that may have potential effects on patient test results. Good QC materials have qualities that not only put the system through its paces but also provide valid information on the system’s performance.
QC materials of composition (or matrix) equivalent to patient samples minimize possible matrix effect interferences. The best QC materials are also stable with expiration dates at least one year into the future and have well-characterized shelf life stability after their original storage conditions change whether through thawing, reconstitution or storage in an opened bottle. Labs need to evaluate common sources of QC material variability up front and mitigate this variability by statistically assessing new lots of QC and by standardizing procedures for handling the materials.
It is possible for labs to prepare homemade QC as long as they are willing to take care of all the associated logistics, which may be labour intensive initially. Labs that take this route need to identify the source of and desired concentrations for the analyte in question, consider the matrix and stability of the QC materials, and characterize their storage and stability criteria through a well-documented study that includes acceptability criteria, evaluates stability at different temperatures during short- and long-term storage, and analyzes the effect of temperature changes if the QC will be subjected to these (e.g. freeze-thaw cycles).
Clinical Chemistry
Urine test reveals what you really eat
A urine test that can reveal how healthy your meals are has been developed by UK scientists, in a collaboration between Imperial College London, Newcastle University and Aberystwyth University. The researchers believe it could be used to improve nutritional advice or in weight loss monitoring because people are notoriously bad at recording their own eating habits.
Published in the Lancet Diabetes and Endocrinology, the test uses urine samples which are analyzed by a technique known as proton nuclear magnetic resonance spectroscopy. For the study, four diets of varying degrees of healthiness were given to the patients and their urine was sampled morning, noon and night. The scientists were able to spot the difference between healthy and unhealthy diets after tests on 19 people who spent days eating a carefully controlled set of meals.
Dr. Desmond Walsh, from the UK Medical Research Council, commented: "Though this research is still in its early stages, it's grappling with essential methods in food and diet studies where advances are really needed… Measuring what we eat and drink more accurately will widen the benefits of nutrition research, developing better evidence-based interventions to improve an individual's health and reduce obesity."
Transfusion Medicine
Transfusions of 'old' blood may harm some patients
The oldest blood available for transfusions releases large and potentially harmful amounts of iron into patients' bloodstreams, a new study by researchers at Columbia University Medical Center (CUMC) has found.
Based on the new findings, the researchers recommend that the FDA reduce the maximum storage limit of red blood cells from 6 weeks to 5 weeks, as long as there are sufficient blood supplies available. "Our recommendation will be controversial, but we think we have real data to support it," said the study's co-leader Dr. Steven Spitalnik, professor of pathology & cell biology at CUMC. "Recent studies have concluded that transfusing old blood has no impact on patient outcomes, but those studies didn't exclusively examine the oldest blood available for transfusions. Our new study found a real problem when transfusing blood that's older than 5 weeks."
In the study, the researchers randomly assigned a group of 60 healthy volunteers to receive a unit of red blood cells that had been stored for 1, 2, 3, 4, 5, or 6 weeks. The volunteers were then monitored for 20 hours after transfusion. Within hours after transfusion, 7 of the 9 volunteers who received the 6-week-old blood could not appropriately metabolize the damaged cells, thereby releasing large amounts of iron into their bloodstream. Only one volunteer who received younger blood had a similar response, with blood that had been stored for five weeks. "Based on the amount of iron circulating in the blood of the volunteers who received 6-week-old blood, we'd predict that certain existing infections could be exacerbated," said Dr. Eldad Hod, associate professor of pathology & cell biology at CUMC.
The true impact of 6-week-old blood on the rate of complications in patients is likely to be small, the researchers say, but since millions of Americans receive transfusions each year, even a 1% difference in complications could affect a large number of patients.
Microbiology
Ebola can linger in lungs, study finds
An unprecedented Ebola virus (EBOV) outbreak occurred in 2013–2016 in West Africa. Researchers say they've discovered signs that EBOV could lurk in the lungs and reproduce in a recovering patient. The results were published in PLOS Pathogens.
In order to better understand EBOV infection patterns in different body compartments, the researchers longitudinally explored the presence of already assessed markers of ongoing EBOV replication (negative sense genomic RNA and positive sense RNA) in the upper and lower respiratory tract, as compared to plasma and other body compartments. This was done in a health care worker infected with EBOV in Sierra Leone, who was hospitalized in the high isolation facility of the National Institute for Infectious Diseases, Lazzaro Spallanzani (INMI), Rome, Italy. Plasma samples, nasopharyngeal swabs, ocular swabs and urine samples were collected daily (starting from day 1, day 3, day 1 and day 1, respectively) while sputum samples were repeatedly collected (starting from day 4) throughout hospitalization.
The presence of total EBOV RNA and replication markers was observed in specimens of the lower respiratory tract, even after viral clearance from plasma, suggesting possible local replication. The investigators found signs that the virus lingered in the lungs for almost a week after it was no longer found in the patient's blood. "This suggests a major role of the respiratory tissues in the pathogenesis of Ebola virus disease," the study authors wrote, referring to the way the virus takes hold in the body. The researchers said they still want to understand the significance of lung infection and whether it plays a role in spreading Ebola.
New method accurately detects prions in blood
Prion diseases are a group of rare, fatal brain diseases that affect animals and humans. They are caused by normally harmless proteins that become abnormal and form clumps in the brain. One form, called variant CJD (vCJD), is associated with eating meat from cattle infected with bovine spongiform encephalopathy, commonly known as “mad cow” disease.
The only current method to diagnose vCJD is to perform a biopsy or a postmortem analysis of brain tissue. Thus, a noninvasive test to detect prions in blood is a medical priority. Two research groups recently developed blood tests to detect prions. The results appeared in a pair of papers published in Science Translational Medicine. Both research teams developed methods to amplify the prions in blood samples using a technique called protein misfolding cyclic amplification (PMCA). PMCA relies on the characteristic nature of prions to cause certain healthy proteins to clump abnormally and convert into prions.
The first group combined healthy proteins with known concentrations of infectious vCJD prions. They intermittently agitated these mixtures with sound waves. The agitation helped break the prions into smaller chunks. This increased the number of prions that could then convert healthy proteins into prions. Using this method, the scientists were able to detect more than a billion-fold dilution of prions using an anti-prion antibody. The test identified 14 people with vCJD and 153 controls correctly.
The second research group described a similar approach testing a blinded panel of blood samples. That team identified 18 vCJD patients in a group of 256 samples.
Molecular Genetics
Genetics play a significant role in immunity, new research finds
Nearly three quarters of immune traits are influenced by genes, new research from King's College London reveals. The study published in Nature Communications, adds to a growing body of evidence that the genetic influence on our immune system is significantly higher than previously thought.
The researchers analyzed 23,394 immune phenotypes in 497 adult female twins from the TwinsUK cohort. In the results, 76% of immune traits show a predominantly heritable influence, whereas 24% are mostly influenced by environment. These data highlight the importance of shared childhood environmental influences such as diet, infections or microbes in shaping immune homeostasis for monocytes, B1 cells, γδ T cells and NKT cells, whereas dendritic cells, B2 cells, CD4+ T and CD8+ T cells are more influenced by genetics. Although leukocyte subsets are influenced by genetics and environment, adaptive immune traits are more affected by genetics, whereas innate immune traits are more affected by environment.
The findings could help to improve understanding of the immune system and the interaction of environmental factors. It could also form the basis of further research into treatments for various diseases, including rheumatoid arthritis and psoriasis.
Safety
The patient safety aspect of health information technology
While technological advances can increase the ability to ensure patient safety, careful consideration should be given to the development and implementation of new health information technologies. By selecting a platform that meets the needs of all users, health care organizations can improve patient outcomes.
The Institute of Medicine suggests that health informatics vendors should work closely with end-users to ensure usability, interoperability, efficient workflow, and the effective transmission of diagnostic data between all individuals, including the patient, who are involved in the diagnostic process.
Safety issues related to health informatics are often the result of problems encountered during the implementation phase, as well as design flaws. If end-users are not properly trained or if they feel that a system does not meet the requirements that allow them to effectively perform their job, it can lead to the creation of work-arounds that pose a patient safety risk.
Organizations must also promote transparency and accountability regarding patient safety issues involving health informatics errors. The use of health information technologies can be a valuable tool to support patient safety initiatives. By involving individuals from all levels of an organization in the development process, end-users are less likely to demonstrate resistance to new technologies. Focus should be placed on training and adequate testing of functionality prior to implementation. Health informatics offer a plethora of mechanisms that promote patient safety, but the full benefit is recognized only when an organization uses a teamwork approach to development and application.
Thank you!
We appreciate that you have taken the time to read LabBuzz. This is a CSMLS venture to provide relevant medical laboratory news to its members.
We need your help to grow this newsletter! Please pass along the subscription link to any colleague you think would benefit from hearing about med lab news.
If you have any suggestions to improve LabBuzz, we would love to hear from you. In fact, if you have a news or publication link you would like us to consider for a future issue, please send it to labbuzz@csmls.org.