Day: March 23, 2021

Boy’s Brain Rewires After Stroke as a Newborn

Photo by cottonbro from Pexels

Researchers have reported the case of a boy whose brain was able to rewire after a severe stroke that damaged much of his brain.

In the seventh grade, 13-year old Daniel Carr amazed his baseball coach with his ability to throw with his left hand, saying that it was the fastest he’d ever seen. However, he was unable to properly catch with his right hand.

Hearing this from the coach, Kellie Carr, Daniel’s mother, realised that his son had a number of quirks, such as favouring his left side when he was an infant, and his left-handedness emerged well before the normal age of two or three. However, she was unable to get any explanation for this until she met Nico Dosenbach, MD, PhD, who informed her that her son had had a stroke when he was a newborn.

MRI scans revealed large, bilateral voids in Daniel’s brain, but incredibly, he had no cognitive, behavioural or motor problems other than a lack of strength and dexterity in his right arm.
“The extent of Daniel’s injuries may be on the edge of what’s compatible with life,” Dosenbach said.

Dainel’s remarkable recovery can be explained by his young age at the time the stroke.

“The brain can compensate more quickly and completely for strokes sustained in early childhood,” he said. “By contrast, large strokes in adults often cause death or severe functional impairment with little chance of recovery. However, the mechanics behind this are only beginning to be understood.”

More MRI scans were done on Daniel’s brain to determine its structure and pathology. Dosenbach and Laumann conducted high-resolution functional MRI scans to understand how Daniel’s brain had reorganised itself.
With his mother’s consent, Daniel was further tested over a period of six years, including batteries of neurological tests, and more scans done. Timothy Laumann, MD, PhD, now a fourth-year psychiatry resident at Barnes-Jewish Hospital, had the expertise to analyse the data.

Looking at his medical records, the physician-scientists noted that he had an infection as a newborn, and was hospitalised with an IV drip. However, none of the physicians had suspected a stroke, which happens to one in every 4000 newborns. Daniel was sent home after a week, the doctors having suspected a viral infection.

“The risk of having a pediatric stroke greatly increases with a medical problem, especially an infection during the newborn period,” Dosenbach said. “However, usually there are more obvious signs that a stroke occurred. I can understand how no one suspected it.”

The researchers compared the images of Daniel’s brain to others of young adults, as well as Dosenbach’s own brain, which he had imaged and studied extensively.

“Part of Daniel’s brain structure is gone,” Laumann explained, referring to their analysis of the MRI data. “He’s missing almost a quarter of his cortex.”

The dead tissue was replaced by pockets of cerebrospinal fluid, which acts as a shock absorber, as well as delivering nutrients and removing waste. The surviving neurons formed interconnected islands that restored cognitive and motor functions, and neighbourhoods of healthy tissue were again reconnected.

“Our findings illustrate the brain’s tenacity at reorganizing and recovering functions damaged by a massive stroke affecting both sides of his brain,” Dosenbach said. “Future studies of functional remapping relative to tissue loss may provide additional insights. Our results raise the possibility that variability in outcomes may depend on specific features unique to an individual’s brain.”

Despite the extensive damage, Daniel completed tertiary education and now works as a diesel mechanic.

“His stroke still shocks me,” Kellie Carr said. “How could I have not known? But looking back, maybe it was better that way. I might have babied Daniel and been afraid to let him be a regular kid. Maybe the best thing for him was living normally.”

Daniel agreed: “I think about my right hand daily because I have to constantly think five steps ahead to figure out how to compensate for not being able to use it properly, like I did with the baseball glove. But the last thing I want is for people to act like something is wrong with me. I’m fine.”

Source: Medical Xpress

Journal information: Timothy O Laumann et al. Brain network reorganisation in an adolescent after bilateral perinatal strokes, The Lancet Neurology (2021). DOI: 10.1016/S1474-4422(21)00062-4

COVID Vaccines and Vaccination Certificates Sold on Darknet

According to an article by BBC News, COVID vaccines and vaccination certificates are being widely sold on the darknet.

Prices can range from  $500 (R7500) and $750 for doses of the AstraZeneca, Sputnik, Sinopharm or Johnson & Johnson vaccines. Some even allow for emergency delivery with an overnight service. There are also fake vaccination certificates being sold for as little as $150.

Also known as the ‘dark web’, the darknet is a part of the internet that can only be accessed with specific browser tools. One such tool is Tor, a browser specially designed for anonymity.

Cyber-security company Checkpoint says that they have seen the number of adverts triple from when vaccines first become available, to 1200. The sources of the adverts appear to be the US, UK, Spain, Germany, France and Russia.

Oded Vanunu, head of product vulnerabilities research at Check Point told the BBC: “It’s imperative for people to understand that attempting to obtain a vaccine, a vaccination card or negative Covid-19 test result by unofficial means is extremely risky, as hackers are more interested in your money, information and identity for exploitation.”

Mr Vanunu also shared that,  as part of their research, his team purchased a Sinopharm vaccine dose from one of the vendors for $750, but are yet to receive it. His team believes that this particular vendor was a scammer, but others might be selling real vaccines.

Check Point is urging countries to protect their vaccine documentation by implementing a QR code system to make forgeries more difficult.

Source: BBC News

Asymptomatic Carriers are the Biggest Barrier to Containing COVID

The lack of testing in asymptomatic carriers makes it harder to control SARS-CoV-2 spread, according to researchers at the Georgetown Center for Global Health Science and Security, Georgetown University in Washington.

Two groups of individuals dominate the transmission of COVID: asymptomatic carriers, who do not develop any symptoms throughout the course of their infection; and presymptomatic carriers, who develop symptoms a few days after being infected.

Transmission without symptoms makes it difficult to estimate the infectious timeline and potential exposures. Asymptomatic cases may likely mingle with others oblivious to their infection, promoting virus spread. They may also not adhere to social distancing, mask wearing etc. Contact tracing is vital to monitor the spread of the disease, and asymptomatic cases makes surveillance to analyse secondary attack rates highly challenging.

Though there is no accurate reporting on the prevalence of asymptomatic cases available, early studies showed that they made up so 30% to 80% of infections. More recent evidence put asymptomatic cases at 17% to 30% of infections.

In COVID cases, the infectious period begins two days before symptom onset and several days thereafter, though viral shedding is reduced in the first week of symptoms.

Viral shedding in asymptomatic cases is poorly understood, however it is known that asymptomatic cases have the same viral load as symptomatic cases, regardless of severity. In asymptomatic individuals, infectious periods are shorter due to reduced titers at peak replication and faster viral clearance.

Some studies have shown that asymptomatic individuals are 42% less likely to infect others and have lower secondary attack rates, while other research indicates that, despite the shorter infectious periods, asymptomatic individuals have similar transmissibility to those who are presymptomatic.
The researchers note that symptomatic individuals were motivated to seek testing, treatment and self-isolate upon feeling COVID symptoms.

“With many contagious people experiencing no symptoms and in the absence of robust surveillance testing for asymptomatic or presymptomatic infections, it is critical to maximising efforts to reduce transmission risk in the community,” noted the researchers.

Source: Medical-News.Net

Journal information: Rasmussen, A., and Popescu, S. (2021). SARS-CoV-2 transmission without symptoms. Science. https://science.sciencemag.org/content/371/6535/1206

‘Feed-forward’ Loop in Cartilage Cells Worsens Osteoarthritis


An unfortunate ‘feed-forward’ loop in cartilage cells appears to exacerbate arthritis, according to researchers Duke University and Washington University in Saint Louis.

Cartilage resists compressive forces, enhances bone resilience, and provides support on bony areas where there is a need for flexibility. In osteoarthritis, the most common form of arthritis,  the cartilage breaks down, allowing painful bone-on-bone contact. Osteoarthritis is the and affects millions of people worldwide with joint pain and stiffness. It is most commonly found in the knees, hips and spine.  

Chondrocytes build and maintain cartilage, with force-sensitive ion channels on their surface, which are called Piezo1 and Piezo2. Piezo channels respond to mechanical loads on the joint by sending signals into the cell that can change gene activity.

In osteoarthritis, degeneration and malfunction of chondrocytes, which are unable to repair themselves by division, contributes to the progressive breakdown of cartilage. Osteoarthritis is als marked by chronic, low-grade inflammation, driven by interleukin-1 alpha, a signalling molecule. Taking cartilage cells from pigs and from human joints removed for replacement surgeries, the researchers investigated the way inflammation affects chondrocytes.

The researchers found that interleukin signaling causes the chondrocytes to produce more Piezo channels, in turn increasing their sensitivity to pressure and resulting in what the researchers term a harmful ‘feed-forward’ loop that leads to further cartilage breakdown.

“Interleukin reprograms the chondrocytes so that they’re more sensitive to mechanical trauma,” Liedtke said. “The feed-forward cycle slowly grinds them down and the cell cannot be replaced.”

Liedtke likened healthy chondrocyte to “a tennis ball”, a bouncy sphere which is kept stiff by its internal matrix of actin fibres. But as these cells lose their ability to replace actin fibres, “they get softer, more squishy.”

However, more Piezo channels were created as the chondrocytes became squishier.

“Overexpressed Piezo channels render the inflamed chondrocyte hypersensitive to mechanical microtrauma, thus increasing the risk of mechanically-induced chondrocyte injury and subsequent progression of osteoarthritis,” said  first and co-corresponding author and biomedical engineer, Whasil Lee, who moved from the Liedtke-Lab to open her own laboratory at the University of Rochester

“It’s cartilage reprogramming itself to do more damage,” Liedtke said.

To confirm this relationship, the researchers blocked the activity of the Piezo channels and observed that the ‘squishiness’ of chondrocytes was reverted.

“We have known that mechanical loading of the joint is essential for maintaining cartilage health,” Guilak said. “In this study, we have uncovered a mechanism by which excessive loading under inflammatory conditions can create a situation that can lead to progressive cartilage degeneration.”

“We’re always looking for feed-forward mechanisms as facilitators of chronic disease,” Liedtke said. “Here we found one, which opens the door for us to come up with disease-modifying treatments, currently non-existent for osteoarthritis.”

Source: Duke University

Journal information: “Inflammatory Signaling Sensitizes Piezo1 Mechanotransduction in Articular Chondrocytes as a Pathogenic Feed-Forward Mechanism in Osteoarthritis,” Whasil Lee, et al. PNAS, March 22, 2021, DOI: 10.1073/pnas.2001611118

Edible Food Film Packaging Developed as Alternative to Plastic

Researchers from India and Russia have created edible food films for packaging fruits, vegetables, poultry, meat, and seafood. 

These films are made up of natural ingredients, and as such are safe for health and the environment. In addition, these films are water-soluble and dissolve by almost 90% over 24 hours. A description of their research and the results of their experiments are published in the Journal of Food Engineering.

Using such films would help to reduce the problem of microplastics, micrometre-scale fragments of plastic which have been detected in human stools as well as inhaled through the lungs.Chemicals such BPAs, phthalates and flame retardants, as well as heavy metals included in plastics are of concern to human health. The increased surface area/volume ratio of microplastics in combination with their hydrophobicity, results in a high affinity with a broad range of hydrophobic and persistent organic pollutants, antibiotics, and heavy metals that could be introduced into the human body through the uptake of microplastics.

“We have created three types of food films based on the well-known naturally occurring seaweed biopolymer sodium alginate. Its molecules have film-forming properties. Sodium alginate is an auspicious carbohydrate macromolecule that has the potential film-forming properties upon hydrolysis and abundantly existed in cell walls as a mixture of various salts. The greatest advantage of sodium alginate is that it performs as liquid-gel in an aqueous medium.”

Rammohan Aluru, Study Co-Author and Senior Researcher of Organic Synthesis Laboratory, Ural Federal University

The researchers cross-linked alginate molecules with a natural antioxidant ferulic acid, resulting in a strong and homogeneous film that is more rigid and prolongs the life of the products. However, being able to produce edible, naturally sourced films also has other benefits.

“Food stays fresh longer due to the antioxidant components that slow down the oxidation processes,” said Grigory Zyryanov, professor of the Department of Organic and Biomolecular Chemistry at Ural Federal University. “In addition, we can add to the films natural antiviral agents that will also extend the shelf life of food. Garlic, turmeric, and ginger contain compounds that may prevent the spread of the viruses.”

No special equipment for the production of films is required, the authors claim, and can be scaled up to an industrial scale by manufacturers of  food products and films.

“It can also be produced at a polymer production plant. The only condition is that it must meet the standards that apply to food production. And if an inexhaustible source of algae the ocean is nearby it will be quite simple to create such films,” said Prof Zyryanov.

Source: News-Medical.Net

Journal information: Yerramathia, B. B., et al. (2021) Structural studies and bioactivity of sodium alginate edible films fabricated through ferulic acid crosslinking mechanism. Journal of Food Engineering. doi.org/10.1016/j.jfoodeng.2021.110566.

Patients Might Benefit From Thrombectomy in Basilar Strokes

Despite the disappointing results of the BEST and BASICS trials for basilar artery occlusion strokes, in some cases, patients might benefit from endovascular therapy (EVT) after all, according to a closer look at the data.

Raul Nogueira, MD, of Grady Memorial Hospital and Emory University School of Medicine in Atlanta, and colleagues in the VERITAS group, presented their findings at the American Stroke Association virtual International Stroke Conference.

On adjusted intention-to-treat analysis, among the 351 stroke patients with baseline NIH Stroke Scale (NIHSS) scores of ≥ 10, having EVT showed a 38.7% chance of zero-to-moderate disability modified Rankin Scale [mRS] 0-3) at 90 days compared to 26.5% with best medical management (adjusted OR 1.94).

EVT also offered a mortality reduction benefit over controls (40.3% vs 48.2%), although at the risk of increased risk of symptomatic intracranial hemorrhage (5.0% vs 0.6%). Subgroup analysis suggested that older patients tended to have especially good outcomes with EVT.

Based on the study’s results, it does appear “that some patients with basilar artery occlusion strokes benefit from mechanical thrombectomy,” commented Steven Hetts, MD, of UCSF Mission Bay Hospitals in San Francisco.

“The trends do appear to be toward favoring EVT in selected patients, which is consistent with our earlier experience in anterior circulation large vessel occlusion [LVO] strokes,” he noted.

Given how rare they are, posterior circulation LVO strokes are challenging to study, and are also characterised by complex symptoms and severity.

Nogueira noted that the BEST and BASICS were underpowered as they had suffered from poor recruitment, crossovers, and selection issues. Additionally, the BASICS trial had undergone a protocol modification to allow recruitment of people with milder strokes (NIHSS <10), which had potentially diluted the treatment effect. An important point which had been missed was that underlying atrial fibrillation was more prevalent at baseline among the EVT arm than controls.

This implies “that their basilar occlusions may more likely have been from embolization of a clot from the heart to an otherwise normal basilar artery,” according to Dr Hetts. “I would expect that those patients would do better clinically than patients with underlying atherosclerotic disease in the basilar artery itself that leads to basilar artery occlusion.”

Source: MedPage Today

Presentation information: Nogueira RG, et al “Vertebrobasilar occlusion randomization to endovascular reperfusion versus intravenous thrombolysis or medical treatment alone systematic evaluation (VERITAS) collaboration” ISC 2021; Abstract LB 11.