Tag: lab tests

Stemming the Flow of the ‘Spice’ Drug

The ‘spice’ drug, which has dangerous side effects, is becoming more popular around the world, partly due to the difficulty in detecting its presence.

Spice is the street name for one type of synthetic cannabinoids (SC), which a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently used published data to develop SC variations marketed as abusable ‘designer drugs’. In the early 2000’s, SC became popular as ‘legal highs’, partly due to their ability to escape detection by standard cannabinoid screening tests. While they provide a similar ‘high’ to cannabis, they are seen as safer but in fact they have serious and potentially fatal side effects.

In 2019, the team developed a prototype of their spice-detecting device and found it could detect the drug from saliva and street material in under five minutes. The current test involves lab analysis of urine, with results after three to seven days.

Dr Chris Pudney from the University’s Department of Biology & Biochemistry, and creator of the new technology, said faster testing is essential if users are to receive treatment and harm-reduction interventions.

“There is no way of knowing if spice has been taken if someone presents with psychosis or intoxication symptoms that could also be due to other reasons,” said Dr Pudney. “So we see the detection technology as a way to inform care in case of overdose.”

The test’s obvious advantages have resulted in great interest, resulting in a grant which the Bath research team will use to create a simple field-usable testing solution.

Dr Pudney said: “Spice is endemic in homeless communities and prisons. It’s highly potent, addictive and poses severe health risks to users including psychosis, stroke, epileptic seizures and can kill. We want to deliver a detection system both to raise the prospect of rapid treatment and to stem the flow of drugs in these communities.”

There are also recent reports of children ‘mistaking’ spice for cannabis, resulting in numerous hospital admissions.

“Drug testing and checking, which is increasing in many countries around the world and in the UK, has been shown to have an impact on drug-taking behaviour and to potentially reduce risk,” said Dr Jenny Scott from the University’s Department of Pharmacy & Pharmacology and who is also involved in the research.

“Spice use is a particular issue in homeless communities. In the future, we hope our technology can be used to offer drug testing to spice users and to tailor harm-reduction information to these vulnerable people. The machines could be used in drugs services, homeless hostels and further down the line, in pharmacies.”

The new spice-testing technology will be based on a cloud-hosted data analytics platform.

“We hope to combine this technology with a deeper understanding of the communities that use spice so that we can deploy the spice-detecting technology in the most effective way possible to benefit the most vulnerable in society,” said Dr Pudney. “Our ultimate aim is to save both money and lives.”

By the end of the grant period, the group aims to start a not-for-profit social enterprise to bring their technology to the mainstream. The group plans to roll out the full range of activities needed to deliver the technology, including portable device design, analytical software development, chemical fingerprint libraries and the associated community pharmacy practice advice to deploy the technology effectively.

“We believe the scope and potential of our research is truly unique and presents the best chance for tackling spice use in the UK and more widely,” said Dr Chris Pudney.

Source: News-Medical.Net

New Bioluminescent System Illuminates Biological Processes

Scientists at the Federal University of São Carlos (UFSCar) have developed a new bioluminescent system that can enable greatly improved imaging of biological and pathological processes in organisms.

Luciferases are enzymes that catalyse the oxidation of luciferins present in organisms such as fireflies, which results in bioluminescence in the visible light spectrum. Images of cell cultures and live animal models are made using the luciferin-luciferase system found in fireflies. For example, this can show the structure and activity of tumours, or follow the viral process in cells, helping physicians develop treatments.

“We obtained a novel luciferin-luciferase system that produces far-red light at the wavelength of 650 nanometres and emits the brightest bioluminescence ever reported in this part of the spectrum,” said principal investigator Professor Vadim Viviani, biochemist at UFSCar. “It’s a highly promising result for bioluminescence imaging of biological and pathological processes in mammalian tissues.”

“Red bioluminescence is preferred when imaging biological or pathological processes in mammalian tissues because haemoglobin, myoglobin and melanin absorb little long-wavelength light. Detection is best of all in the far red and near-infrared bands, but bioluminescent systems that naturally emit far red light don’t exist,” Prof Viviani added.

“Some genetically modified forms of luciferase and synthetic analogs of natural luciferins are produced commercially. In conjunction, they produce light at wavelengths as long as 700 nanometers, but the light produced by these artificial systems is generally much weaker and more short-lived than light from natural bioluminescent systems.”

Prof Viviani and collaborators genetically modified luciferase from the Railroad worm Phrixothrix hirtus, the only luciferase that naturally emits red light, and combined with luciferin analogues synthesised by colleagues at the University of Electro-Communications in Tokyo. The resulting luciferin-luciferase generates a much more efficient far-red bioluminescence.

“Our best combination produces far-red at 650 nanometres, three times brighter than natural luciferin and luciferase, and roughly 1000 times brighter than the same luciferase with a commercial analog,” Viviani said.

“Besides the long-wavelength and intense brightness, our combination has better thermal stability and cell membrane penetrability. Above all, it produces more lasting continuous bioluminescence, taking at least an hour to decay and significantly facilitating the real-time imaging of biological and pathological processes.”

Source: News-Medical.Net

Journal information: Viviani, R. V, et al. (2021) A Very Bright Far-Red Bioluminescence Emitting Combination Based on Engineered Railroad Worm Luciferase and 6′-Amino-Analogs for Bioimaging Purposes. International Journal of Molecular Sciences. doi.org/10.3390/ijms22010303.

New Test Picks up Concussion Biomarkers in Saliva

A new test has been found to effectively pick up concussion biomarkers in the saliva of rugby players.

This paves the way for a non-invasive, easy-to-use pitch-side test to rapidly detect concussions for early treatment. Concussion is a serious problem in contact sports, with players such as college American Football athletes consistently underestimating its risk. Missing a concussion can have a range of consequences, from delayed recovery to more serious (albeit rare) injuries such as traumatic brain swelling.

Detecting concussions requires an assessment by a clinician of the signs and symptoms of the injury. However, recent advances in DNA sequencing technology have made it possible to use small non-coding RNAs (sncRNAs) as biomarkers in rapid tests. sncRNAs regulate the expression of different cellular proteins associated with various diseases, such as cancer and Alzheimer’s disease.

t is thought that since saliva can receive cellular signals directly from the cranial nerves in the mouth and throat, biomarkers from a brain injury would quickly show up.

A panel of 14 sncRNAs differentiated concussed players from those where traumatic brain injury had been suspected but ruled out, and from the comparison group, both straight after the game and 36–48 hours later.

Over two seasons, samples were collected before the rugby season began from 1028 players from the two elite professional tiers, and during standardised ‘gold standard’ head injury assessments at three time points—during the game, afterwards, and 36–48 hours later from 156 of these players .

The researchers also took saliva samples from a comparison group of 102 uninjured players, as well as 66 with muscle or joint injuries, and so had not had head injury assessments.

However, the researchers stressed that the observational study nature and design of this study cannot show that the biomarker test is any better than a gold standard clinical test for concussion.

“In community sport, [sncRNAs] may provide a non-invasive diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting,” while the test could be added to current head injury evaluation protocols at the elite level,” they add.

And as the biology of concussion is still not fully understood, sncRNAs might help to shed light on the response to injury as this evolves over time, they suggest.

“The detection of signatures of concussion at early time points in saliva (a non-invasively sampled biofluid) presents both at the pitch side, and in primary care and emergency medicine departments, an opportunity to develop a new and objective diagnostic tool for this common clinical presentation,” they conclude.

As an addendum to their findings, they added: “A patented salivary concussion test is in the process of being commercialized as an over-the-counter test for elite male athletes.

“Meanwhile our research team aims to collect further samples from players in two elite men’s rugby competitions to provide additional data to expand the test and develop its use. This will guide the prognosis and safe return to play after concussion and further establish how the test will work alongside the head injury assessment process.”

The researchers plan to add more participants to the SCRUM study, such as female athletes and community players.
Source: Medical Xpress

Journal information: Valentina Di Pietro et al. Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM), British Journal of Sports Medicine (2021). DOI: 10.1136/bjsports-2020-103274

New French COVID Variant Invisible to PCR Tests

French authorities have announced the detection of a variant of SARS-CoV-2 in the northwestern region of Brittany that has escaped detection by standard polymerase chain reaction (PCR) tests.

Real-time PCR tests are considered to be the current gold standard for detection of SARS-CoV-2, and currently take 4-6h to yield a result. PCR tests make millions to billions of copies of a small sample of DNA to create a larger sample for analysis.

Eight carriers of the variant were identified using genomic sequencing among a cluster of 79 cases in the town of Lannion in the Côtes d’Armor on March 13th.

In a statement on Monday, the French health ministry said that according to initial analyses, the new variant did not appear more transmissible or cause more severe disease. However, on Tuesday, authorities said that this variant was able to escape detection in PCR tests is raising concern.

Belgian virologist and interfederal COVID spokesperson Steven Van Gucht clarified the situation, in that about eight individuals presented with standard coronavirus symptoms, “but the tests remained negative.”

The World Health Organization has labelled this new French COVID variant a ‘variant under investigation’ (VUI), of which there are many thousands currently being monitored, as opposed to more serious variants like the South African B.1.351 variant which is more transmissible and is a ‘variant of concern’ (VOC).

However, just because this variant escaped the PCR tests being used in that area does not mean that it necessarily can escape all of them, as laboratories vary in the tests that they perform.

According to Gucht, tests differ in the different parts of the virus they look for, and also test for at least two to three. “Usually, a good test does not depend on detecting one specific part. So, if there is a mutation in one part of the virus, that signal may be lost, but there is usually a second or third signal that will be found,” explained Gucht.

French authorities are setting up systems to monitor the spread of this variant, and are also putting measures in place to contain it.

Source: News-Medical.Net

Delaying Lumbar Puncture Cuts Relapse in Childhood Leukaemia

Commencing chemotherapy several days before the first lumbar puncture for diagnosis and treatment of acute lymphoblastic leukaemia (ALL) may lower the risk of central nervous system (CNS) relapse in children, according to a study from St Jude Children’s Research Hospital and collaborators in China. 

“This study identified factors to help us predict and better manage the risk of CNS relapse that will be useful for treating ALL patients worldwide, in both resource-rich and resource-limited countries,” said corresponding author Ching-Hon Pui, MD, chair of the St. Jude Department of Oncology. Dr Pui pioneered paediatric ALL treatment that has achieved 94% long-term survival for St. Jude patients that did not receive brain irradiation.

Using an adapted paediatric protocol from St Jude Hospital, 7640 children and adolescents across 20 Chinese hospitals were enrolled in the trial. However, there was a great disparity across the hospital settings. For example, just three of the hospitals offered total intravenous anaesthesia for children undergoing spinal taps, while only two had flow cytometry for the diagnosis of leukaemia cells in cerebrospinal fluid.

The five-year overall survival rate was 91% for study patients, and the cancer-free survival rate was 80%, which is a dramatic improvement over previous clinical trials in China. But 1.9% of patients relapsed in the CNS alone, and in another 2.7% of patients the relapse involved the CNS. In comparison, a Canadian study reported a 6.6% rate for CNS-involved relapse in paediatric ALL patients followed over 10 years.

According to Dr Piu, in order to increase the survival rate of paediatric ALL patients requires identifying those at risk for CNS relapse, along with increasing their quality of life. Three factors reduced the risk of CNS relapse. First, commencing dexamethasone a few days before the spinal tap, prevents leukaemia cells entering the cerebrospinal fluid (CSF). Second, intravenous anaesthesia reduced bleeding risk during lumbar punctures, and improved  intrathecal therapy. Third, flow cytometry enables more accurate diagnosis of leukaemia cells in CSF, and reduced CNS relapse.

Source: Medical Xpress

Journal information: Jingyan Tang et al. Prognostic Factors for CNS Control in Children with Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation, Blood (2021). DOI: 10.1182/blood.2020010438

Optimised Scheduling Algorithm Cuts Delays for MRI Scans

A team of researchers from Dartmouth Engineering and Philips have developed an optimised scheduling algorithm that significantly cuts the waiting time of patients for MRI at Lahey Hospital in Massachusetts, cutting overall associated costs by 23%.

“Excellence in service and positive patient experiences are a primary focus for the hospital. We continuously monitor various aspects of patient experiences and one key indicator is patient wait times,” said Christoph Wald, professor and chair, Department of Radiology, Lahey Hospital, Tufts University Medical School. With a goal of wanting to improve patient wait times, we worked with data science researchers at Philips and Dartmouth to help identify levers for improvement that might be achieved without impeding access.”

Exam waiting times can be stressful for patients, depending on the perceived value of the visit, and the associated costs of a delay to the patient.

Before the new algorithm, the average outpatient’s waiting time at the hospital was 54 minutes. The researchers found that the problem was a complicated scheduling system, which must cater to emergency room patients, inpatients, and outpatients; while other appointments are relatively inflexible, inpatient exams usually can be delayed if necessary.
“By analysing the patient data, we found that delays were prominent because the schedule was not optimal,” explained first author Yifei Sun, a Dartmouth Engineering PhD candidate. “This research uses optimisation and simulation tools to help the MRI centres of Lahey Hospital better plan their schedule to reduce overall cost, which includes patient waiting time.”

After identifying sources of delays, the researchers then created a mathematical model which optimised the length of each exam slot, and then worked in inpatient exams. Then they created an algorithm which cut down on the waiting time with its associated costs for outpatients, idle equipment time, employee overtime, and cancelled inpatient exams.

“This iterative improvement process did result in measurable improvements of patient wait times,” said Prof Wald. “The construction and use of a simulation model have been instrumental in educating the Lahey team about the benefits of dissecting workflow components to arrive at an optimised process outcome. We have extended this approach to identify bottlenecks in our interventional radiology workflow and to add additional capacity under the constraints of staffing schedules.”

The researchers believe that this solution may have great applicability, as the problem is common to mid-sized hospitals.

“We also provided suggestions for hospitals that don’t have optimisation tools or have different priorities, such as patient waiting times or idle machine times,” said Sun, who worked on the paper with her advisor Vikrant Vaze, the Stata Family Career Development Associate Professor of Engineering at Dartmouth.

Source: News-Medical.Net

Journal information: Sun, Y., et al. (2021) Stochastic programming for outpatient scheduling with flexible inpatient exam accommodation. Health Care Management Science. doi.org/10.1007/s10729-020-09527-z.

New Study Finds Critical Flaw in Blood-brain Model

The wrong kind of cells have been used to make in vitro models of the blood-brain barrier, which now throws a decade’s worth of research into question.

The present in vitro human blood-brain barrier model was developed in 2012. By inducing differentiated adult cells, such as skin cells, into developing into stem cells, the pluripotent stem cells obtained from the process are then transformed into nearly any type of mature cell. This includes the type of endothelial cell that lines brain and spinal cord blood vessels, and making a unique barrier that acts as a gatekeeper, restricting potentially dangerous substances, antibodies, and immune cells from entering the brain from the bloodstream.

“The blood-brain barrier is difficult to study in humans and there are many differences between the human and animal blood-brain barrier. So it’s very helpful to have a model of the human blood-brain barrier in a dish,” said co-study leader Dritan Agalliu, PhD, associate professor at Columbia University Vagelos College of Physicians and Surgeons.

Agalliu had noticed that these endothelial cells produced in this manner, did not behave like normal endothelial cells in the human brain. “This raised my suspicion that the protocol for making the barrier’s endothelial cells may have generated cells of the wrong identity,” said Agalliu.
“At the same time the Weill Cornell Medicine team had similar suspicions, so we teamed up to reproduce the protocol and perform bulk and single-cell RNA sequencing of these cells.”

Upon analysis, the researchers discovered that the supposed human brain endothelial cells were missing several key proteins found in natural endothelial cells and had more in common with epithelial cells, which is not usually found in the brain.

The team also identified three genes that, when activated within induced pluripotent cells, lead to the creation of cells that behave more like actual endothelial cells. More work is still needed, Agalliu says, to create endothelial cells that produce a reliable model of the human blood-brain barrier. His team is working to address this problem.

“The misidentification of human brain endothelial cells may be an issue for other types of cells made from induced pluripotent cells such as astrocytes or pericytes that form the neurovascular unit,” said Agalliu. The protocols to produce these cells were drawn up prior to the advent of single-cell technologies that are better at identifying cells.

“Cell misidentification remains a major problem that needs to be addressed in the scientific community in order to develop cells that mirror those found in the human brain. This will allow us to use these cells to study the role of genetic risk factors for neurological disorders and develop drug therapies that target the correct cells that contribute to the blood-brain barrier.”

Source: Medical Xpress