Tag: 24/6/24

Categories : NeurologyTags : Leave a comment

Visual Cortex Stimulation Boosts Brain-computer Interface

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Deep brain stimulation illustration. Credit: NIH

Brain-computer interfaces, or BCIs, promise life-changing benefits for people suffering from a range of neurological conditions, but implementation is for both the invasive and noninvasive methods is challenging. Researchers led by Bin He at Carnegie Mellon University used an innovative electroencephalogram (EEG) wearable. They successfully integrated a novel focused ultrasound stimulation to realise bidirectional BCI that both encodes and decodes brain waves using machine learning in a study with 25 human subjects.

This work, published in Nature Communications, opens up a new avenue to significantly enhance not only the signal quality, but also, overall nonivasive BCI performance by stimulating targeted neural circuits.

Noninvasive BCI is lauded for its merits of being cheap, safe, and virtually applicable to everyone, but because signals are recorded over the scalp versus inside the brain, low signal quality presents some limitations. The He group is exploring ways to improve the effectiveness of noninvasive BCIs and, over time, has used deep learning approaches to decode what an individual was thinking and then facilitate control of a cursor or robotic arm.

In their latest research, the He group demonstrated that through precision noninvasive neuromodulation using focused ultrasound, the performance of a BCI could be improved for communication.

“This paper reports a breakthrough in noninvasive BCIs by integrating a novel focused ultrasound stimulation to realise bidirectional BCI functionality,” explained Bin He, professor of biomedical engineering at Carnegie Mellon University. “Using a communication prosthetic, 25 human subjects spelled out phrases like ‘Carnegie Mellon’ using a BCI speller. Our findings showed that the addition of focused ultrasound neuromodulation significantly boosted the performance of EEG-based BCI. It also elevated theta neural oscillation that enhanced attention and led to enhanced BCI performance.”

For context, a BCI speller is a 6×6 visual motion aide containing the entire alphabet that is commonly used by nonspeakers to communicate. In He’s study, subjects donned an EEG cap and just by looking at the letters, were able to generate EEG signals to spell the desired words. When a focused ultrasound beam was applied externally to the V5 area (part of the visual cortex) of the brain, the performance of the noninvasive BCI greatly improved among subjects. The neuromodulation-integrated BCI actively altered the engagement of neural circuits to maximize the BCI performance, compared to previous uses, which consisted of pure processing and decoding recorded signals.

Following this discovery, the He lab is further investigating the merits and applications of focused ultrasound neuromodulation to the brain, beyond the visual system, to enhance noninvasive BCIs. They also aim to develop more compact-focused ultrasound neuromodulation device for better integration with EEG-based BCIs, and to integrate AI to continue to enhance the overall system performance.

“This is my lifelong interest, and I will never give up,” emphasized He. “Working to improve noninvasive technology is difficult, but I strongly believe that if we can find a way to make it work, everyone will benefit. I will keep working, and someday, noninvasive lifesaving technology will be available for every household.

Source: College of Engineering, Carnegie Mellon University

Categories : Ethics and LawTags : Leave a comment

Discovery Health says Road Accident Fund in Breach of Court Order

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Photo by Bill Oxford on Unsplash

By Tania Broughton

Discovery Health had an “overwhelming case” against the Road Accident Fund (RAF) and its CEO Collins Letsoalo showing it was clearly in breach of a 2022 court ruling that the fund was not allowed to withhold payments for past medical expenses from road accident victims who had been paid out by their medical schemes.

This was the submission of Advocate Wim Trengove, on behalf of Discovery, at a special court hearing seeking to hold the fund and Letsoalo to account.

While initially Discovery, in its application before Gauteng Judge President Dunstan Mlambo and judges Ingrid Opperman and Noluntu Bam on Thursday, were seeking orders of contempt of court, Trengrove said it was now only seeking an order of “breach” and to compel compliance.

He said this would give Letsoalo a further opportunity to “have his say” as to why he should not be found in contempt and possibly jailed for it.

In 2022, Judge Mandla Mbongwe ruled in the Pretoria High Court that a new directive – effectively refusing to pay for past medical expenses of those claimants already paid out by medical aids – was unlawful.

The RAF was unsuccessful in its appeals to both the Supreme Court of Appeal and the Constitutional Court.

Read the original Pretoria High Court judgment here

Trengove argued that the RAF had continued to implement the directive, regardless of the court ruling.

“We have a list of about 20 cases, all of which are in line with the Mbongwe judgment,” he said.

After the apex court refused to grant the RAF leave to appeal the Mbongwe judgment, two further “directives” came to light in which the fund seemingly sought to side-step the legal implications of the Mbongwe judgment.

Trengove said “directive two” was also raised once in litigation and was rejected. Under this directive, the fund had argued that it should not have to compensate medically insured victims if they had been paid out in accordance with prescribed minimum benefits.

“Then it produced ‘directive three’ which is equally spurious,” he said.

This was based on a section of the RAF Act, which prohibited compensation to anyone who had agreed to share compensation with another person. The fund argued that the agreement between a medical scheme and its members fell foul of this.

“But that agreement is merely an agreement to avoid double-compensation. That the medical aid pays upfront and if the member recovers (from the fund), then that member will reimburse the medical aid,” Trengove said.

He said regardless, the new directive did not absolve the fund from complying with the Mbongwe ruling.

That ruling, he said, confirmed that a claim against the fund is a claim in delict: the fund steps into the shoes of the wrongdoer, and “the perpetrator is not entitled to benefit from the insurance proceeds of the victim”.

“Our courts have held that medical schemes, for the purposes of claims, are akin to insurance, and claims cannot be taken into account when determining the quantum of liability,” Trengove said.

RAF denial

But advocate Cedric Puckrin, who appeared with advocate Gerhard Cilliers for the fund, said Trengove had argued his case “with rose-coloured glasses”.

Cilliers said the fund was entitled to implement the first directive during the period when the appeal process had been underway.

He said Discovery was arguing a new case, not an enforcement of the Mbongwe ruling, and had based it on ten examples where the fund had responded to letters of demand by claimants, indicating that it would dispute liability for any claim for past medical expenses.

Cilliers suggested that Discovery had no standing in court, and that it was up to individual claimants to take their matters to court.

He also said the ten examples did not show that the fund was in breach.

“It is not Discovery’s case that RAF is enforcing the 2022 directive. It wants you to go further and ask you to find that the subsequent directives are the same. And we submit that is not the proper process to follow. It is an abuse of the process.”

Advocate Puckrin argued that while the third directive might be “entirely wrong”, it was a different directive which could only be set aside by a separate application to the court.

He said it could not be considered a “breach” of the Mbongwe judgment.

But Judge Opperman suggested that it was just a “new piece of paper” dealing with the same issue.

“But it’s based on a new principle,” Puckrin said. “It’s far more limited.”

In reply, Trengove said the Mbongwe judgment has set out a statement of “general principle” that the fund could not free itself from paying full compensation to medical aid members.

He said Letsoalo and other fund officials had made a series of public statements which reflected their “unlawful disdain” for the ruling.

“A delinquent public body cannot insulate itself against compliance with a court order by adopting a directive in effect not to comply with it. It is contrary to the rule of law.”

Judgment was reserved.

Republished from GroundUp  under a Creative Commons Attribution-NoDerivatives 4.0 International License.

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Categories : Exercise Pain ManagementTags : Leave a comment

Walking is Highly Effective for Stopping Low Back Pain from Returning

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Photo by Henry Xu on Unsplash

New research from Macquarie University’s Spinal Pain Research Group shows that walking has the potential to change the way low back pain is managed, making effective interventions accessible to more people than ever before. The results of the trial, which combined walking with education, are published in The Lancet.

About 800 million people worldwide have low back pain, which is a leading cause of disability and reduced quality of life. Recurrences of low back pain are very common, with seven in 10 people who recover from an episode going on to have a recurrence within a year.

Professor of Physiotherapy Mark Hancock and his research team have been investigating ways to shift the emphasis from treatment to prevention to improve the management of back pain, an approach that empowers individuals to manage their own health and reduces the cost to society and the healthcare system.

Far from the bed rest recommended for back pain in the past, current best practice includes the combination of exercise and education, both to treat current pain and to prevent future episodes.

While beneficial, some forms of exercise are not accessible or affordable to many people due to their high cost, complexity and need for supervision.

A simpler, more accessible method

The world-first WalkBack trial examined whether a programme of walking combined with education could be effective in preventing recurrences of low back pain.

The trial followed 701 adults who had recently recovered from an episode of low back pain, randomly allocating participants to either an individualised walking program facilitated by a physiotherapist and six education sessions across six months, or to a no-intervention control group.

The participants’ progress was then followed for between one and three years to collect information about any new recurrences of low back pain they experienced.

The researchers’ primary aim was to compare the two groups for the number of days before participants experienced a recurrence of back pain that impacted daily activities or required care from a healthcare provider.

They also evaluated the cost effectiveness of the intervention, including costs related to work absenteeism and healthcare services.

Longer pain-free periods

The paper’s senior author, Professor Hancock, says what they discovered could have a profound impact on how low back pain is managed.

“The intervention group had fewer occurrences of activity-limiting pain compared to the control group, and a longer average period before they had a recurrence, with a median of 208 days compared to 112 days,” Professor Hancock says. “The risk of having a recurrence that required seeking care was nearly halved in those in the intervention group.

“Walking is a low-cost, widely accessible and simple exercise that almost anyone can engage in, regardless of age, geographic location or socio-economic status.

“We don’t know exactly why walking is so good for preventing back pain, but it is likely to include the combination of gentle oscillatory movements, loading and strengthening the spinal structures and muscles, relaxation and stress relief, and the release of ‘feel-good’ endorphins.

“And of course, we also know that walking comes with many other health benefits, including cardiovascular health, improved bone density, maintenance of a healthy weight and improved mental health.”

Professor Hancock said the amount of walking each person completed was individualised based on a range of factors including their age, physical capacity, preferences and available time. Participants were given a rough guide to build up to 30 minutes, five times a week over a six-month period.

After three months, Professor Hancock said most of the people who took part were walking three to five days a week for an average of 130 minutes.

“You don’t need to be walking five or 10 kilometres every day to get these benefits,” Professor Hancock says.

A cost-effective option

The paper’s lead author, Postdoctoral Fellow Dr Natasha Pocovi, says in addition to providing participants with longer pain-free periods, they found the program was also cost effective.

“It not only improved people’s quality of life, but it reduced their need both to seek healthcare support and the amount of time taken off work by approximately half,” Dr Pocovi says.

“The exercise-based interventions to prevent back pain that have been explored previously are typically group-based and need close clinical supervision and expensive equipment, so they are much less accessible to the majority of patients.

“Our study has shown that this effective and accessible means of exercise has the potential to be successfully implemented on a much larger scale than other forms of exercise.”

To build on these findings, the team now hopes to explore how they can integrate the preventive approach into the routine care of patients who experience recurrent low back pain.

Source: MacQuarie University

Categories : TransplantsTags : Leave a comment

Gut Bacteria Enzymes to Turn Donated A and B Blood Universal

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Photo by Charliehelen Robinson on Pexels

The quest to develop universal donor blood has taken a decisive step forward. Researchers in Denmark have discovered enzymes that, when mixed with red blood cells, are able to remove specific sugars that make up the A and B antigens in the human AB0 blood groups. The results appear in Nature Microbiology.

“For the first time, the new enzyme cocktails not only remove the well-described A and B antigens, but also extended variants previously not recognised as problematic for transfusion safety. We are close to being able to produce universal blood from group B donors, while there is still work to be done to convert the more complex group A blood. Our focus is now to investigate in detail if there are additional obstacles and how we can improve our enzymes to reach the ultimate goal of universal blood production,” says Professor Maher Abou Hachem, who is the study leader at Technical University Denmark (DTU) and one of the senior scientists behind the discovery.

He states that the discovery is the result of combining the expertise of DTU researchers in enzymes from the human gut microbiota and Lund University researchers in carbohydrate-based blood groups and transfusion medicine.

High demand for donor blood

Human red blood cells carry specific complex sugars structures (antigens) that define the four AB0 blood groups A, B, AB and 0. These antigens control compatibility between donors and recipients for safe blood transfusion and organ transplantation. Donor blood is screened for disease markers and the main blood groups. It can then be stored refrigerated for up to 42 days.

The need for donor blood is high due to the elderly making up a larger proportion of the population and more patients undergoing blood-intensive medical procedures. Successfully converting A or B blood types into AB0 universal donor blood can markedly reduce the logistics and costs currently associated with storing four different blood types. In addition, the development of universal donor blood will lead to an increased supply of donor blood by reducing the waste of blood approaching its expiry date.

The reason why it is necessary to remove the A and B antigens to create universal donor blood is because they can trigger life-threatening immune reactions when transfused into non-matched recipients.

The concept of using enzymes to generate universal donor blood was introduced more than 40 years ago. Since then, higher efficiency enzymes to remove the A and B antigens were discovered, but researchers are still not able to explain or abolish all immune reactions related to the blood, and therefore these enzymes are still not used in clinical practice.

Enzymes from the gut

The research groups from DTU and Lund University have gone new ways to find enzymes that can remove both the A and B blood antigens and the sugars that block them. The research teams discovered new mixtures of enzymes from the human gut bacterium Akkermansia muciniphila that feeds by breaking down the mucus, which covers the surface of the gut. It turns out that these enzymes are exceptionally efficient, as the complex sugars at the surface of the intestinal mucosa share chemical resemblance with those found at the surface of blood cells.

“What is special about the mucosa is that bacteria, which are able to live on this material, often have tailor-made enzymes to break down mucosal sugar structures, which include blood group AB0 antigens. This hypothesis turned out to be correct,” says Maher Abou Hachem.

The researchers in this study tested 24 enzymes, which they used to process hundreds of blood samples.

“Universal blood will create a more efficient utilisation of donor blood, and also avoid giving AB0-mismatched transfusions by mistake, which can otherwise lead to potentially fatal consequences in the recipient. When we can create AB0-universal donor blood, we will simplify the logistics of transporting and administering safe blood products, while at the same time minimizing blood waste” says Professor Martin L. Olsson, the leader of the study at Lund University.

The researchers from DTU and Lund University have applied for a patent on the new enzymes and the method for enzyme treatment and expect to make further progress on this in their new joint project over the next three and a half years. If successful, the concept needs to be tested in controlled patient trials before this can be considered for commercial production and clinical use.

The initial research project is funded by the Independent Research Fund Denmark (Technology and Production Sciences, FTP), the Swedish Research Council, ALF grants from the Swedish government and county councils as well as the Knut and Alice Wallenberg Foundation and Research Fund Denmark, Natural Sciences, FNU), while the new continued project is funded by the Novo Nordisk Foundation, Interdisciplinary Synergy Programme.

The AB0 blood group antigens found on the surface of red blood cells are also found on the mucosal layer that lines the surface of the gut. Researchers have harnessed a specialised human gut bacterium and its ability to use these antigens as nutrients to discover and develop two enzyme mixtures that convert group A and B red blood cells into universal donor blood. Graphic: Mathias Jensen, postdoc at DTU.

About Akkermansia muciniphila

Akkermansia muciniphila is a bacterium found abundantly in the guts of most healthy humans. This bacterium can break down mucus in the gut and produces beneficial compounds such as the short-chain fatty acid propionate, in addition to exerting beneficial effects on body weight and metabolic markers.

Source: Technical University of Denmark

Categories : Metabolic DisordersTags : Leave a comment

Study Trials First Drug Therapy for Sleep Apnoea

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Photo by Ketut Subiyanto on Pexels

In an international phase III study, researchers have demonstrated the potential of tirzepatide, known to manage type 2 diabetes, as the first effective drug therapy for obstructive sleep apnoea (OSA), a sleep-related disorder characterised by repeated episodes of irregular breathing due to complete or partial blockage of the upper airway.

The results, published in the New England Journal of Medicine, highlight the treatment’s potential to improve the quality of life for millions around the world affected by OSA.

“This study marks a significant milestone in the treatment of OSA, offering a promising new therapeutic option that addresses both respiratory and metabolic complications,” said Atul Malhotra, MD, lead author of the study, professor of medicine at University of California San Diego School of Medicine and director of sleep medicine at UC San Diego Health.

OSA can result in reduced blood oxygen levels and can also be associated with an increased risk of cardiovascular complications, such as hypertension and heart disease. Recent studies, also led by Malhotra, suggest that the number of OSA patients worldwide is close to 936 million.

Conducted in two Phase III, double-blinded, randomised, controlled trials, the new study cohort recruited 469 participants from 9 countries with clinical obesity and living with moderate-to-severe OSA. Participants either used or did not use continuous positive airway pressure (CPAP) therapy, the most common sleep apnoea treatment which uses a machine to maintain an open airway during sleep, preventing interruptions in breathing. Patients were administered either 10 or 15mg of the drug by injection or a placebo and followed for 52 weeks.

Researchers found that tirzepatide led to a significant decrease in the number of breathing interruptions during sleep, a key indicator used to measure the severity of OSA. This improvement was much greater than what was seen in participants that were given a placebo. Importantly, some participants that took the drug reached a point where CPAP therapy might not be necessary. Considerable data suggest that a drug therapy that targets both sleep apnoea and obesity is beneficial rather than treating either condition alone.

Additionally, the drug therapy improved other aspects related to OSA, such as reducing the risk factors of cardiovascular diseases and improved body weight. The most common side effect reported was mild stomach issues.

“Historically, treating OSA meant using devices during sleep, like a CPAP machine, to alleviate breathing difficulties and symptoms,” Malhotra said. “However, its effectiveness relies on consistent use. This new drug treatment offers a more accessible alternative for individuals who cannot tolerate or adhere to existing therapies. We believe that the combination of CPAP therapy with weight loss will be optimal for improving cardiometabolic risk and symptoms. Tirzepatide can also target specific underlying mechanisms of sleep apnoea, potentially leading to more personalised and effective treatment.”

Malhotra adds that having a drug therapy for OSA represents a significant advancement in the field. 

“It means we can offer an innovative solution, signifying hope and a new standard of care to provide relief to countless individuals and their families who have struggled with the limitations of existing treatments,” said Malhotra. “This breakthrough opens the door to a new era of OSA management for people diagnosed with obesity, potentially transforming how we approach and treat this pervasive condition on a global scale.”

Next steps include conducting clinical trials to examine longer term effects of tirzepatide.

Source: Atrium Health Wake Forest Baptist