Day: February 15, 2021

Plasma microRNAs as Biomarkers for Mild Brain Injury

Plasma microRNA could serve as biomarkers for the detection and diagnosis of mild traumatic brain injury, a recent study from the University of Eastern Finland (UEF) has found.

Mild traumatic brain injury is extremely difficult to detect as it is almost invisible to most imaging techniques, and visible signs in daily life may be masked by compensation for increased task difficulty.

Blood biomarkers can satisfy the demand for timely, accurate, easily accessible and affordable tests for mild traumatic brain injury. They are minimally invasive and can provide molecular information about the injury on an ongoing basis.

MicroRNAs (miRNAs) are non-coding sections of RNA that play a key role in gene expression. The researchers sequenced DNA in blood plasma taken from animal models subjected to mild and severe traumatic brain injury. They selected the miRNAs which showed the greatest potential for use as biomarkers for further analysis with polymerase chain reaction (PCR). They wanted biomarkers that were both sensitive and specific to traumatic brain injury in an animal model.

Dr Noora Puhakka, A. Virtanen Institute for Molecular Sciences, UEF, said, “We have been developing a suitable analysis and measurement method especially for miRNAs that can be found in small amounts in plasma, and this method is based on digital droplet PCR.

“Humans and animals share many identical miRNAs, and this makes them excellent candidates for translational studies, where results achieved in animal models are sought to be applied in humans. However, it has proven challenging to reproduce results from different studies and different sets of data. This is why assessing the quality of measurement methods, and reproducibility, is an extremely important part of biomarker research.”
The study a pair of possible biomarker candidates to diagnose mild traumatic brain injury both in the animal model and in human patients.  

“We found two interesting biomarkers in the animal model, the plasma miRNAs miR-9a-3p and miR-136-3p, which we then decided to analyse in blood samples taken from patients with traumatic brain injury. Elevated levels of these biomarkers allowed us to identify some of the patients who had experienced a mild traumatic brain injury,” Dr Puhakka explained.

“Both of these miRNAs are more abundant in the brain than in other tissues, and their elevated levels in plasma could possibly be due to brain injury and the level of its seriousness. However, further research in larger patient cohorts is still needed.”

Source: News-Medical.Net

Journal information: Gupta, S. D., et al. (2021) Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury. International Journal of Molecular Sciences. doi.org/10.3390/ijms22041563.

‘Epidemic Situation’ in Guinea after Cases of Ebola

Recent confirmed cases of an Ebola outbreak have resulted in an epidemic being declared, with governments and health organisations racing to prepare.

After an emergency meeting Sakoba Keita, head of Guinea’s National Health Security Agency, stated: “Very early this morning, the Conakry laboratory confirmed the presence of the Ebola virus.”

In late January, one person had died in Gouécké, near the Liberian border. The victim was buried on 1 February “and some people who took part in this funeral began to have symptoms of diarrhoea, vomiting, bleeding and fever a few days later”, Keita said.

Laboratory testing of samples revealed the presence of Ebola in some of them on Friday, said Keita. He added that, with a total of seven cases and three deaths, Guinea was now in an “Ebola epidemic situation”.

WHO representative Alfred George Ki-Zerbo said in a press briefing: “We are going to rapidly deploy crucial assets to help Guinea, which already has considerable experience [treating the disease]. The arsenal is stronger now and we will take advantage of that to contain this situation as fast as possible.

“The WHO is on full alert and is in contact with the manufacturer [of a vaccine] to ensure the necessary doses are made available as quickly as possible to help fight back.”

Ebola is also flaring up outside of Guinea. On Thursday, the WHO announced a resurgence of Ebola in the DRC, only three months after the outbreak there was declared over. In Guinea’s neighbour Liberia, health authorities have been put on high alert even though no cases have as yet been detected there. 

The deadly Ebola outbreak of 2013-2016 prompted the creation of a global stockpile of 500 000 vaccine doses, which can be drawn upon whenever an outbreak of the disease occurs.

Source: The Guardian

Brain ‘Rewired’ by Sound Early in the Womb

Playing music to foetuses in the womb to enhance their brain development is a popular practice even if thus far not grounded in science, but new research has shown that there may be some effect even at very early stages.

New research from John Hopkins University indicates that ‘wiring changes’ made in response to sounds occur even earlier than thought before. The ear canals of newborn mice only open after 11 days, while in humans, the ear canals open at 20 weeks’ gestation. The researchers used the mice as a model for human foetuses, and examined their neural connections at one week old.

“As scientists, we are looking for answers to basic questions about how we become who we are,” said Patrick Kanold, PhD, professor of biomedical engineering at The Johns Hopkins University and School of Medicine. “Specifically, I am looking at how our sensory environment shapes us and how early in foetal development this starts happening.”

Prof Kanold started out in electrical engineering before switching to neuroscience. His field of research is on the cortex, the outer layer of neurons underneath which lies the white matter which consists of connective neurons.

In developing foetuses, in the white matter, subplate neurons can be found at 12 weeks in human gestation and the second embryonic week in mice. This subplate neurons are the precursors to neurons and die off over a period lasting from before birth to several months old. Before they disappear, they make a connection between the thalamus, which is an important sensory gateway, and the middle layers of the cortex.

“The thalamus is the intermediary of information from the eyes, ears and skin into the cortex,” explained Prof Kanold. “When things go wrong in the thalamus or its connections with the cortex, neurodevelopmental problems occur.”

The subplate neurons respond to sound before the cortical neurons, prompting two questions for Prof Kanold: When sound signals reach the subplate neurons, does anything happen, and can a change in sound signals reflect changes in the brain circuits at these young ages?

To answer these questions, the researchers used mice genetically engineered to be deaf, unable to convert sound into nerve signals. In deaf, week-old mice, there were 25-30% more connections between subplate and cortical neurons.

“When neurons are deprived of input, such as sound, the neurons reach out to find other neurons, possibly to compensate for the lack of sound,” said Prof Kanold. “This is happening a week earlier than we thought it would, and tells us that the lack of sound likely reorganises connections in the immature cortex.”

To compare the difference extra auditory stimuli made, the researchers put 2-day old pups in a quiet enclosure or an enclosure with a constant beeping sound. There were differences between the subplate neuron connections for beeping and quiet enclosure mice, but not as great as between the deaf and hearing mice. The quiet enclosure mice had stronger connections between the subplate and cortical neurons, similar to the deaf mice. The mice in the beeping enclosure also had a greater diversity in neural circuitry.

“In these mice we see that the difference in early sound experience leaves a trace in the brain, and this exposure to sound may be important for neurodevelopment,” explained Prof Kanold.

The researchers are planning to examine how sound in early development impacts the brain in later life, as well as how sounds in the womb influences neural wiring. This has application for cochlear implants for children born deaf. They also plan to study premature infants neural wiring problems and develop biomarkers for abnormal subplate neuron development. 

Source: Medical Xpress

Journal information: Early peripheral activity alters nascent subplate circuits in the auditory cortex, Science Advances (2021). DOI: 10.1126/sciadv.abc9155

Women are Better ‘Mind Readers’ Than Men, Study Finds

Women are better at ‘reading minds’ than men, finds a new study aimed at better understanding social interaction and the challenges faced by people with autism. 

Sometimes known in the field of psychology as ‘mentalising‘, the process is when people try to ascertain what others are really thinking, for example when they are sarcastic or even lying. Mind-reading has some basis in neuroscience: for example, some research indicates that sensitivity to social interactions is associated with the posterior superior temporal sulcus, an area of the brain which is also known to process biological motion. Everybody has some proficiency with mind reading, and some are inherently better than others. However, some lack the ability to a point where it becomes difficult to function in society, for example in autism.

The study made use of a self-report questionnaire asking participants to rate how well, for example, they could relate to others. It used four questions, each with ratings from one to four, giving a maximum total score of 16. The researchers determined that women scored higher than men on the questionnaire, and also confirmed the challenges reported by those with autism. 

Senior author Dr Punit Shah, at the University of Bath’s Department of Psychology explained: “We will all undoubtedly have had experiences where we have felt we have not connected with other people we are talking to, where we’ve perceived that they have failed to understand us, or where things we’ve said have been taken the wrong way. Much of how we communicate relies on our understanding of what others are thinking, yet this is a surprisingly complex process that not everyone can do.”

Dr Shah emphasised that there is a different between mind-reading and empathy, saying: “Mind-reading refers to understanding what other people are thinking, whereas empathy is all about understanding what others are feeling. The difference might seem subtle but is critically important and involves very different brain networks. By focussing carefully on measuring mind-reading, without confusing it with empathy, we are confident that we have just measured mind-reading. And, when doing this, we consistently find that females reported greater mind-reading abilities than their male counterparts.”

Lead researcher, Rachel Clutterbuck, emphasised the clinical importance of the questionnaire. She said: “This new test, which takes under a minute to complete, has important utility in clinical settings. It is not always obvious if someone is experiencing difficulties understanding and responding to others—and many people have learnt techniques which can reduce the appearance of social difficulties, even though these remain.

“This work has great potential to better understand the lived experience of people with mind-reading difficulties, such as those with autism, whilst producing a precise quantitative score that may be used by clinicians to identify individuals who may benefit from interventions.”

Dr Shah added that this study was about helping to understand mind-reading capabilities, and had created a freely available questionnaire for other efforts in this regard.

Source: Medical Xpress

Journal information: Rachel A. Clutterbuck et al, Development and validation of the Four-Item Mentalising Index., Psychological Assessment (2021). DOI: 10.1037/pas0001004

Research Shows ‘UK Variant’ is up to 70% Deadlier

A review of research on the COVID variant B.1.1.7, also known as ‘the UK variant’, has shown it to be 30% to 70% more deadly than the original wild-type COVID strain.

Concerns over the deadliness of B.1.1.7 were raised in January, when the UK government’s New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) presented initial findings suggesting that B.1.1.7 cases were deadlier than non-variant cases. After this, they released an updated report which is available online. The report makes the cases that the earlier linked community testing and mortality data were all based on the same datasets, and so had the same biases. However, the group explained that the new analysis was more valid.

“More recent analyses have added a wider range of data sets and been able to control for additional confounders, increasing confidence in the association of the [variant of concern] with increased disease severity,” the group wrote.  

London School of Hygiene & Tropical Medicine found a relative hazard of mortality within 28 days was 1.58 for variant-infected individuals, while Imperial College London used a case-control weighting method to find a case fatality ratio of 1.36 for variant cases. Public Health England  found a “death risk ratio” of 1.65 in matched cohort analysis for variant cases versus non-variant cases.

A number of other studies investigated the variant’s impact on hospitalisation. Public Health Scotland used S-gene target failure as a proxy for variant case detection. They found that S-gene target failure cases had a higher risk for hospitalisation than the S-gene positive cases.
Some studies did not support the higher fatality risk, such as the UK’s Office for National Statistics (ONS), which said that “the number of deaths are too low for reliable inference.”

A number of limitations were reported in the study, including potential bias in case ascertainment, representativeness, unmeasured confounders and secular trends. They also tried to control for nursing home status in hospital reports, but not all of these could be excluded.

“There are potential limitations in all datasets used but together these analyses indicate that it is likely that … B.1.1.7 is associated with an increased risk of [hospitalisation] and death compared to infection with non-[B.1.1.7] viruses,” the group concluded.

In mid-January, modelling by the CDC indicated that the UK variant would become the dominant strain in the United States by March. At the end of January, President Joe Biden had pledged to increase vaccinations to 1.5 million per day, a target which would still not be able to contain the spread of the variant.

Source: MedPage Today

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WHO Team in China Denied Key COVID Information

The World Health Organization team sent to China to investigate the origins of the COVID virus have been frustrated in their efforts to secure key data.

Team member Dominic Dwyer, infectious disease expert, said that they had only been given a summary instead of the raw patient data that they had requested.

Raw, anonymised patient data is part of standard outbreak investigation, Dwyer said, and this was particularly important because half of the initial 174 patients had no contact with the wet market.

“That’s why we’ve persisted to ask for that,” said Dwyer. “Why that doesn’t happen, I couldn’t comment. Whether it’s political or time or it’s difficult.”

Although Wuhan is the site of the initial outbreak, China has sought to cast doubt on its origin there, pointing to a source outside the country that may have come in with frozen food.

US national security adviser Jake Sullivan said that he had “deep concerns” over the initial findings of the investigation, saying that “It is imperative that this report be independent, with expert findings free from intervention or alteration by the Chinese government.”

Peter Ben Embarek, the WHO delegation leader, said that the virus likely had an animal origin and may have taken a “very long and convoluted path involving also movements across borders”. The possibility that it may have travelled in frozen food is worth investigating, he added.

After their two week quarantine, the WHO team members were only allowed to go on visits organised by their Chinese hosts. Thea Kolsen Fischer, an immunologist and another WHO team member, said to the New York Times that she saw the investigation as “highly geopolitical”.

“Everybody knows how much pressure there is on China to be open to an investigation and also how much blame there might be associated with this,” she said.

Team member Peter Daszak, and president of the EcoHealth Alliance, said that it “was not my experience”.

“As lead of animal/environment working group I found trust and openness with my China counterparts. We did get access to critical new data throughout,” he tweeted.

“New data included environmental and animal carcass testing, names of suppliers to Huanan market, analyses of excess mortality in Hubei, range of Covid-like symptoms for months prior, sequence data linked to early cases and site visits with unvetted live question and answer.”

Source: The Guardian