Tag: 24/3/21

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

Implanting and Erasing False Memories

A technique both to implant and false memories has been described by researchers.

False memories are a source of great confusion for neurologists and psychologists, but interest in them has greatly increased in the past three decades. They are believe to arise from a need for completeness in memory, as well as other factors such as wish fulfillment. Psychologists have demonstrated techniques to instil false memories in subjects, enabling the process to be studied. Such techniques have also been used to influence witnesses in criminal trials.

Functional MRI studies of false memories indicate the involvement of prefrontal cortex, particularly ventromedial and in the right hemisphere.
The method involves planting a suggestion that a plausible event happened, and then using a trusted source to back up the claim. The study used this method with 52 participants, creating plausible stories from their childhood and mixing in real events. The participants’ parents were asked to back up the memories of the false events, and over a number of sessions, many participants gradually began to believe the stories and some also produced false memories.

The researchers found that they could erase these memories by identifying the source of the false memory, then explaining to them how false memories can be created when people are asked to recall a memory several times.  

Interviewing the subjects a year later, the researchers found that 74% of them had either rejected the false memories or forgotten them.

Source: Medical Xpress

Journal information: Aileen Oeberst et al. Rich false memories of autobiographical events can be reversed, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2026447118

‘Zombie’ Genes Lurch into Activity After Brain Death

Researchers have found that genes in cells in recently harvested brain tissue remained active for up to 24 hours – and some ‘zombie’ genes even increased their expression.

Using recently harvested brain tissue as a surrogate for actual death, the researchers investigated the activity of genes.

Dr Jeffrey Loeb, the John S Garvin Professor and head of neurology and rehabilitation at the UIC College of Medicine and corresponding author on the paper, noticed along with his team that the pattern of gene expression in fresh human brain tissue differed from published reports of postmortem brain gene expression from people without neurological disorders or from people with a wide variety of neurological disorders, ranging from autism to Alzheimer’s.

“We decided to run a simulated death experiment by looking at the expression of all human genes, at time points from zero to 24 hours, from a large block of recently collected brain tissues, which were allowed to sit at room temperature to replicate the postmortem interval,” Dr Loeb said.

They found that some ‘zombie’ genes were more expressed after the simulated death. These were specific to glial cells, which have an inflammatory role. The researchers observed that these cells continued to grow long arm-like appendages for many hours after death.

“That glial cells enlarge after death isn’t too surprising given that they are inflammatory and their job is to clean things up after brain injuries like oxygen deprivation or stroke,” said Dr Loeb.

Dr Loeb is director of the UI NeuroRepository, which preserves human brain tissues from patients with neurological disorders who gave their consent to use their tissue after death, or during surgery to treat disorders such as epilepsy, where some brain tissue is removed to treat the condition in lesionectomy. This procedure involves removing structural brain lesions — typically malformations of cortical development, low-grade neoplasms, or vascular malformations. Some of the tissue harvested through these various means can be used for research, as in this study.

About 80% of genes, many of which are involved in cellular ‘housekeeping’ activities, kept functioning up to 24 hours after death. Another group of genes involved in cognition and seizure control faded within a few hours of death. These are important to the study of schizophrenia and Alzheimer’s disease, according to Dr Loeb.

The ‘zombie’ genes ramped up activity as the others were winding down, with these changes peaking at 12 hours.

“Our findings don’t mean that we should throw away human tissue research programs, it just means that researchers need to take into account these genetic and cellular changes, and reduce the post-mortem interval as much as possible to reduce the magnitude of these changes,” Dr Loeb said. “The good news from our findings is that we now know which genes and cell types are stable, which degrade, and which increase over time so that results from postmortem brain studies can be better understood.”

Source: Medical Xpress

Journal information: Fabien Dachet et al. Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain, Scientific Reports (2021). DOI: 10.1038/s41598-021-85801-6

Proximity to Deforested Areas Can Increase Outbreak Risk

Aerial view of logging activities. Photo by Pok Rie from Pexels

A new study has found that human proximity to deforested areas poses an increased risk of the outbreak of zoonotic viruses.  

This adds to a growing body of evidence that human encroachment on the natural environment is resulting in zoonotic disease outbreaks.

Deforested areas and even monocultures such as commercial forests planted by humans are linked to the outbreak of diseases, the researchers found.

The researchers explained that a forest’s healthy diverse ecosystem with a range of species, blocks and filters viruses. However, in the case of monocultures where single species of plants are cultivated, like a palm oil plantation, specialist species die off and are replaced by generalists such as rats which then spread pathogens on to humans.

“I was surprised by how clear the pattern was,” said one of the study authors, Serge Morand, of the French National Centre for Scientific Research. “We must give more consideration to the role of the forest in human health, animal health and environmental health. The message from this study is ‘don’t forget the forest’.”

Using a number of databases from sources such as the World Health Organization, the researchers analysed the relationship between changes in forest cover, plantations, population and disease around the globe.
Over 1990 to 2016, the study period covered 3884 outbreaks of 116 zoonotic diseases that crossed over into humans and 1996 outbreaks of 69 vector-borne infectious diseases, largely carried by mosquitoes, ticks or flies.

“Everyone in the field of planetary health is worried about what is happening to biodiversity, climate and public health in Brazil,” Morand emphasised. “The stress there is growing. The Amazon is near a tipping point due to climate change, which is not good at all for the world ecosystem. If we reach the tipping point, the outcomes will be very bad in terms of drought, fires and for sure in terms of disease.”

The rainforests of the Congo basin and south-east Asia, and monoculture afforestation projects around the world were also cause for concern. “Our results clearly suggest that it is not only forest clearance that is responsible for outbreaks of infectious diseases, but also reforestation or afforestation, particularly in countries outside the tropical zone,” the paper noted.

Morand’s next study involves examining forest cover with satellite imagery and exploring links with that to disease.

Source: The Guardian

Cardiovascular Diseases in Transgender Youth

Young transgender people face a higher risk of cardiovascular diseases, according to a new study.

Anna Valentine, MD, of the University of Colorado Anschutz Medical Campus in Aurora, presented the findings of her team’s study at the Endocrine Society’s virtual ENDO 2021 meeting. Existing research shows increased cardiovascular risks in adult transgender people.

Researchers found that transgender youths assigned female at birth had a higher risk of obesity compared to cisgender female youths, as well as a nearly doubled chance of polycystic ovary syndrome. However, transgender youth did not have an increased risk of hypertension, dysglycaemia, or liver dysfunction.

These differences could be explained by any number of different mechanisms, Dr Valentine explained. “We know that some youth with gender dysphoria have higher rates of overweight and obesity, and that having overweight and obesity itself increases your risk of having other diagnoses.” It is also known that “youth with gender dysphoria have higher rates of mental health comorbidities … as well as getting less physical activity,” she said.

“And they also may be taking medication that could all influence their cardiometabolic health,” she added.

Adult transwomen taking estradiol are more likely to have higher levels of triglycerides and a higher rate of stroke, blood clots, and myocardial infarction (MI). Adult trans men are at greater risk of elevated triglycerides, low-density lipoprotein cholesterol, and body mass index (BMI), as well as lower high-density lipoprotein cholesterol, and an increased risk of MI.
The data of 4174 paediatric patients (average age of 16) diagnosed with gender dysphoria, were compared with 16 651 cisgender controls. This data came from six large paediatric centres. Participants were matched with four controls.

However, the data did not include information on which participants were receiving hormonal treatment, which is something that Dr Valentine is looking to address in her research.

“We do know that in the adult data, that there is some association with estradiol use and testosterone use with differences in cholesterol parameters, but this is still an emerging field in paediatrics,” Dr Valentine explained. “We have some small single-center studies that sometimes say ‘yes, with hormones we see an increase in BMI,’ but other studies say ‘this section looks very stable on this hormone’.”

“The fact that we have such a large cohort in this multicentre analysis for our next steps, I think it will be really interesting to look at that,” she added.

Source: MedPage Today

Presentation information: Valentine A, et al “Multicenter analysis of cardiometabolic-related diagnoses in transgender adolescents” ENDO 2021.

Ideological Divide in the US Undermines Research

The crucial participation of the public in medical research in the United States may be affected by ideological affiliation, thereby undermining medical research, warn researchers from Washington University in St Louis.

The COVID vaccines were developed in an unprecedentedly short time, and this was made possible partly by the participation of over 70 000 volunteers. However, such successes may be in jeopardy if distinct populations cannot be adequately represented, and these include ideologically-based ones.The

distrust of black Americans towards the medical sector, especially research, has been well documented. There are even calls to remove the very concept of race from medical research as many believe it only serves to entrench certain preconceptions. This study, however, is the first to examine the effect of political ideology on willingness to participate in research.

“Our research shows that conservatives are less willing to participate in medical research than are liberals. This difference is due, in part, to ideological differences in trust in science,” said Matthew Gabel, professor of political science in Arts & Sciences.

Such a divide harbours potential consequences where medical research is concerned.

“An ideological divide in such participation could undermine both the execution and quality of medical research,” Prof Gabel said. “Given the uneven geographic distribution of political ideology, our findings raise important issues for recruiting study participants and developing political support for medical research. It could also threaten the generalisability of medical studies since important types of health behaviours, such as smoking, vary with Americans’ political ideology.”

While the problem had been brewing for decades, it was only until ideological disparities towards the medical field were exposed by the COVID pandemic that it gained widespread attention.  For example, a study found that conservative republicans were three times more likely to refuse a vaccine than the more liberal independents or democrats.

Prof Gabel saw this coming from a long way off. He wanted to better understand why some people were more inclined to participate in medical research than others, and joined with John C Morris, MD, the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology and head of the Alzheimer’s Disease Research Center at the School of Medicine; Catherine M Roe, associate professor of neurology at the School of Medicine; and Stanford University’s Jonathan Goobla.

“The value of research with human subjects depends critically on successful recruitment of a representative group of participants. To do that, we have to know sources of bias in who is recruited and who is likely to accept invitations to participate,” Prof Gabel explained.

The researchers analysed survey data from the July 2014 and September 2015 waves of The American Panel Survey, which asked questions about past and future participation in medical research-related activities. These include a clinical trial for a drug, a long-term observations study, a fundraiser for medical research and blood donation. They also had hypothetical questions about one’s willingness to be an organ donor and willingness to participate in an Alzheimer’s disease study.

They selected 1132 respondents 45 years or older, since only they were old enough to participate in those long-term studies, clinical trials and hypothetical Alzheimer’s Disease study.

Those with conservative ideology are less likely to want to participate in medical research, partly because of their lower levels of trust in science. However this lack of trust only accounted for about a quarter of the effect.

“This means that if we want to reduce or eliminate the ideological difference in participation in medical research, we can do some of that by trying to raise trust in science among conservatives,” said Prof Gabel “But even if we are very effective at doing that, my analysis shows that conservatives will still be less likely to participate for ideological reasons unrelated to trust in science.

“The ideological divide in participation in medical research suggests that clinical trials and other long-term observational studies likely over-represent those with liberal political ideology. This can impact the quality of studies because significant health conditions and behaviours — such as smoking, excessive drinking, diets and mortality rates — differ with political ideology,” Prof Gabel said.

“Given the number and political importance of conservatives, and the relative stability of Americans’ ideological commitments, this divide could signify a significant obstacle for the practice, advance and influence of science in the United States,” Gabel concluded.

Source: News-Medical.Net

Journal information: Gabel, M., et al. (2021) The ideological divide in confidence in science and participation in medical research. Scientific Reports. doi.org/10.1038/s41598-021-82516-6.