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Revolutionary Scottish trial aims to improve outcomes for stroke survivors through exercise

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A trailblazing rehabilitation hub using exercise and other therapies to help boost stroke survivors’ recovery has opened its doors at one of Scotland’s largest hospitals – with evidence already pointing towards its life-changing impact on patients.

The hub is part of a trial being conducted by the University of Strathclyde in partnership with NHS Lanarkshire, to meet the overwhelming demand for intensive stroke rehabilitation.

It’s already known that the sooner a patient can begin stroke rehabilitation, the more likely they are to regain lost abilities, such as speech and movement. It’s a common practice for therapy to start as soon as 24 to 48 hours after a stroke, while a patient is still in hospital.

New National Institute for Health and Care Excellence (NICE) guidelines in the UK suggest stroke patients receive three hours of rehabilitation a day, five days a week.

This is a significant increase from the previous NICE advice of 45 minutes per day.

However, due to the overwhelming demand for rehabilitation, the NHS has struggled to meet the minimum recommended level, with current data suggesting that on average patients receive just 14 minutes of physiotherapy, 13 minutes of occupational therapy, and seven minutes of speech therapy a day.

But the new technology-enriched stroke rehabilitation hub (TERHS) at the University Hospital in Wishaw, which lies 11 miles south east of Glasgow, allows patients to access therapy more quickly at the required frequency.

Just weeks after its launch, proof is already emerging that the hub, which has been designed to holistically address the physical and cognitive harm caused by a stroke, has the potential to positively transform the recovery process for survivors.

Now it’s hoped if further evaluation backs up the preliminary findings the concept could be rolled out not just across Scotland, but all four UK nations within the next two years, putting the NHS at the forefront of treating patients in the chronic stage of stroke recovery.

Dr Gillian Sweeney

Dr Gillian Sweeney, an occupational therapist with NHS Lanarkshire and advanced practitioner for stroke survivors, who has led on the development of the trial and set up the hub, told Agetech World the model could receive a wider launch if health trusts are presented with concrete evidence of its physical and financial benefits.

Referring to the hospital trial currently underway and research being done by the University of Strathclyde’s Department of Biomechanical Engineering into the use of such hubs, Dr Sweeney said: “This is groundbreaking, a life-changing trial for those who have had a stroke. I’m a therapist myself and I’ve worked in the NHS for around 20 years, and what I would say is, we have never been able to deliver enough rehabilitation within the current model and resources, and things are getting more pressurised.

“I think every therapist that works in stroke would probably say ‘We know we are not delivering the level of intensity that we should be.’ We know from evidence that the greater the intensity the better the outcomes.

“But we have been on a hamster wheel for a number of years, and I think we are now at the point where this model, with modest investment – and I don’t want to say within current resources because we need the investment in the equipment and staff to run the groups – but with a realistic, modest investment, could actually achieve those levels of rehab activity that we never foresaw we could do without making a huge investment in staffing for one-to-one treatment.

“For me, the feedback from participants, both within the university and even in the early stages on the hospital ward, is that the difference that makes is massive.

“I think for me, as well, what it does, is that it brings back the person’s control of their own rehabilitation. They have the opportunity to attend this hub and with the minimum amount of support, they are back in control of their own rehab.

“They can choose how often they come for and how long they stay. That, in itself, has been huge.”

Even more remarkable is that participants from the community that have taken part in the university-based study – some of whom suffered a stroke up to a decade ago – have seen functional improvements.

“It wasn’t what we expected to see, but we did,” Dr Sweeney said.

“The study initially was just to look at, ‘is it safe, and do people like it?’ Ten years after a stroke there wasn’t a huge amount of expectation that things like arm function or walking speed would improve.

Dr Andy Kerr working with a stroke survivor at the University of Strathclyde. Credit: University of Strathclyde

“But with the outcome measures we have taken, pretty much everybody has improved in one or more areas.

“If you look at that and think ‘we can make those improvements 10 years down the line,’ what could you do in the very early phases after a stroke when your brain is more likely to make the changes to see improvement?

“For me, it is groundbreaking. If you use this model and put some of this equipment in so people can do the things they need to, it is a total no-brainer.

“Yet it (the resource) is not there. There are reasons for it not being there, and part of that has to do with people within healthcare systems often working so hard and under such pressure they don’t get the space to think about new ways of working or to test them.

“There are traditional ways of working and it takes a long time within the NHS to adopt new ways and to embed that.”

The impact of stroke can be profound and the months immediately after suffering one are key to recovery.

Located within the University Hospital’s stroke unit, the TERHS hub has a virtual reality treadmill with a specialist harness, a balance trainer, and power-assisted equipment from UK-based wellness and wellbeing supplier Innerva, which supports users to exercise allowing them to work passively or actively, depending on where they are in their recovery stage.

The technology also incorporates ‘gamification’, such as virtual reality, puzzles and problem-solving activities, which helps to improve the engagement with and response to therapy.

In addition, the hub houses specialist cognitive and VR equipment, helping to enrich the environment and improve users engagement with and response to rehabilitation therapy.

The hub builds on the research being carried out by the University of Strathclyde which has seen a team led by Dr Andy Kerr and Professor Philip Rowe in the Department of Biomechanical Engineering, set up a gym-like space offering an eight-week programme to survivors under the supervision of Dr Sweeney and research physiotherapist, Mel Slachetka, in the Sir Jules Thorn Centre for Co-Creation of Rehabilitation Technology.

The hospital hub has attracted 15 patient recruits so far, all of whom have been “extremely positive” about the programme, Dr Sweeney said, with some managing three hours of rehabilitation a day.

“People are getting much more activity time than would have been the case. Patients like the Innerva equipment as all they have to do is press a button, and they feel they are in control.

The University of Strathclyde’s technology-enriched rehabilitation hub. Credit: University of Strathclyde

“The setting seems to be popular, and what we are finding is that patients are coming up in a group. Having a stroke can be isolating, but the feedback we are getting is that users value the opportunity to meet people who are going through the same experience as them.

“We know that on stroke wards across the country there isn’t enough staff. Often what happens is that the nursing staff will help patients get out of bed and then they will sit in a chair for hours.

“But with the hub they are using their brain, they are being active, they are off the ward, and they are having the opportunity to socialise.”

The hub can support five patients at a time alongside two support staff.

Given the evidence already accrued through the University of Strathclyde’s rehabilitation programme in which every person using the Sir Jules Thorn Centre facility has seen an improvement, mostly in walking speed but also in some cases speech, it seems difficult to understand why the hub idea isn’t being rolled out as a priority.

Especially as Dr Sweeney admits her ambition is to see technology-driven rehabilitation hubs established in community settings across the UK to provide stroke survivors with easily accessible therapy for optimal recovery.

But whilst the idea may indeed, to quote Dr Sweeney, be a ‘no-brainer,’ even the most obvious concepts need to be proved on a number of levels.

With funding from the Engineering and Physical Science Research Council’s Impact Acceleration Account, a research assistant will assess the impact of the hub on inpatients in the early phase of their recovery with the aim of enabling them to achieve, or even exceed, the recommended levels of rehabilitation.

“We need to look at the costs and the harsh economics,” Dr Sweeney said. “From a research point of view, we must prove that. We are often not very good at proving that something is cost-effective.

“Rehabilitation in general has been run in the same way for a long time and it can be difficult to change traditional practices. And rehabilitation therapists as well as the public can be frightened of technology.

“There is often a feeling that if somebody who has had a stroke is elderly, they won’t be able to cope with technology. But one of our patients is 94, and we are finding that age isn’t as much of a barrier as people may think it is.

“But we need to prove all these things as well as the positive impact this approach can have on stroke survivors. At the minute we have tried it with people who are in the very early stages of stroke rehab, we have tried it in an acute inpatient ward, and we know it is safe and that it is acceptable.

“But we need to prove that people like the hub idea, that they get great intensity of rehabilitation, and that it improves people’s outcomes. Once we do that that will hopefully allow us to make a case that these facilities should be in place.

“Obviously, there are initial costs in terms of buying equipment, and there needs to be a discussion around how do we change the pathways and how do we change the ways the services work to allow this to become part of the normal treatment.

“But at the end of the day, what we want is to keep people out of hospital so they can go home and lead as normal a life as possible in the community.”

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Gut microbes from aged mice induce inflammation in young mice

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Findings from a new study suggest that changes to the gut microbiome play a role in the systemwide inflammation that often occurs with ageing.

When scientists transplanted the gut microbes of aged mice into young “germ-free” mice — raised to have no gut microbes of their own — the recipient mice experienced an increase in inflammation that parallels inflammatory processes associated with ageing in humans. Young germ-free mice transplanted with microbes from other young mice had no such increase.

Published in Aging Cell, the study also found that antibiotics caused longer-lasting disruptions in the gut microbiomes of aged mice than in young mice.

“There’s been a growing consensus that ageing is associated with a progressive increase in chronic low-grade inflammation,” said Jacob Allen, a professor of kinesiology and community health at the University of Illinois Urbana-Champaign who led the new research with Thomas Buford, a professor of medicine at the University of Alabama at Birmingham.

“And there’s a kind of debate as to what drives this, what is the major cause of the ageing-induced inflammatory state. We wanted to understand if the functional capacity of the microbiome was changing in a way that might contribute to some of the inflammation that we see with ageing.”

Previous studies have found associations between age-related changes in the microbial composition of the gut and chronic inflammatory diseases such as Parkinson’s disease and Alzheimer’s disease. Some studies have linked microbial metabolism to an individual’s susceptibility to other health conditions, including obesity, irritable bowel syndrome and heart disease. Age-related changes in the gut microbiome also may contribute to the so-called leaky gut problem, the researchers said.

“Microbiome patterns in aged mice are strongly associated with signs of bacterial-induced barrier disruption and immune infiltration,” they wrote.

“The things that are in our gut are supposed to be kept separate from the rest of our system,” Buford said. “If they leak out, our immune system is going to recognize them. And so then the question was: ‘Is that a source of inflammation?’”

Many studies have compared the relative abundance and diversity of species of microbes in the gut, offering insight into some of the major groups that contribute to health or disease. But sequencing even a portion of the microbes in the gut is expensive and the results can be difficult to interpret, Allen said. That is why he and his colleagues focused on microbial function — specifically, how the gut microbiomes of ageing mice might spur an immune response.

The team focused on toll-like receptors, molecules that mediate inflammatory processes throughout the body. TLRs sit in cellular membranes and sample the extracellular environment for signs of tissue damage or infection. If a TLR encounters a molecule associated with a potential pathogen — for example, a lipopolysaccharide component of a gram-negative bacterium — it activates an innate immune response, calling in pro-inflammatory agents and other molecules to fight the infection.

The researchers first evaluated whether the colonic contents of young and aged mice were likely to promote TLR signalling. They found that microbes from aged mice were more likely than those from young mice to activate TLR4, which can sense lipopolysaccharide components of bacterial cell walls. A different receptor, TLR5, was not affected differently in aged or young mice. TLR5 senses a different bacterial component, known as flagellin.

Young germ-free mice transplanted with the microbes of aged mice also experienced higher inflammatory signalling and increased levels of lipopolysaccharides in the blood after the transplants, the team found.

This finding provides “a direct link between ageing-induced shifts in microbiota immunogenicity and host inflammation,” the researchers wrote.

In other experiments, the team treated mice with broad-spectrum antibiotics and tracked changes in the microbiomes during treatment and for seven days afterward.

“One of the most interesting questions for me was what microbes come back immediately after the treatment with antibiotics ends,” Buford said. And in the mice with aged microbiota in their guts, “these opportunistic pathogens were the most quick to come back.”

“It appears that as we age our microbiome might be less resilient to antibiotic challenges,” Allen said. “This is important because we know that in the U.S. and other Western societies, we’re increasingly exposed to more antibiotics as we age.”

The study is an important step toward understanding how age-related microbial changes in the gut may affect long-term health and inflammation, the researchers said.

Co-authors of the study also included Illinois postdoctoral researcher Elisa Caetano-Silva; U. of I. Ph.D. student Akriti Shrestha; National Children’s Hospital research scientist Michael Bailey; and Jeffrey Woods, the director of the Center on Health, Aging and Disability at Illinois.

Allen also is a professor of nutritional sciences at Illinois and an affiliate of the Carl R. Woese Institute for Genomic Biology at the U. of I.

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Evening exercise benefits elderly hypertensives

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Evening exercise benefits elderly hypertensives

A study conducted at the University of São Paulo with 23 volunteers found that aerobic exercise performed in the evening benefits elderly hypertensives more than morning exercise.

Aerobic training is known to regulate blood pressure more effectively when practiced in the evening than in the morning.

Researchers who conducted a study of elderly patients at the University of São Paulo’s School of Physical Education and Sports (EEFE-USP) in Brazil concluded that evening exercise is better for blood pressure regulation thanks to improved cardiovascular control by the autonomic nervous system via a mechanism known as baroreflex sensitivity.

Leandro Campos de Brito, first author of the article, commented: “There are multiple mechanisms to regulate blood pressure, and although morning training was beneficial, only evening training improved short-term control of blood pressure by enhancing baroreflex sensitivity.

“This is important because baroreflex control has a positive effect on blood pressure regulation, and there aren’t any medications to modulate the mechanism.”

In the study, 23 elderly patients diagnosed and treated for hypertension were randomly allocated into two groups: morning training and evening training. Both groups trained for ten weeks on a stationary bicycle at moderate intensity, with three 45-minute sessions per week.

Key cardiovascular parameters were analysed, such as systolic and diastolic blood pressure, and heart rate after ten minutes’ rest. The data was collected before and at least three days after the volunteers completed the ten weeks of training.

The researchers also monitored mechanisms pertaining to the autonomic nervous system, which controls breathing, heart rate, blood pressure, digestion, and other involuntary bodily functions, such as muscle sympathetic nerve activity, which regulates peripheral blood flow via contraction and relaxation of blood vessels in muscle tissue, and sympathetic baroreflex sensitivity, assessing control of blood pressure via alterations to muscle sympathetic nerve activity.

In the evening training group, all four parameters analysed were found to improve: systolic and diastolic blood pressure, sympathetic baroreflex sensitivity, and muscle sympathetic nerve activity. In the morning training group, no improvements were detected in muscle sympathetic nerve activity, systolic blood pressure or sympathetic baroreflex sensitivity.

“Evening training was more effective in terms of improving cardiovascular autonomic regulation and lowering blood pressure. This can be partly explained as due to an improvement in baroreflex sensitivity and a reduction of muscle sympathetic nerve activity, which increased in the evening. For now, all we know is that baroreflex control is the decisive factor, from the cardiovascular standpoint at least, to make evening training more beneficial than morning training, since it induces the other benefits analysed. However, much remains to be done in this regard in order to obtain a better understanding of the mechanisms involved,” said Brito, who is currently a professor at Oregon Health & Science University’s Oregon Institute of Occupational Health Sciences in the United States, and continues to investigate the topic via circadian rhythm studies.

Baroreflex sensitivity regulates each heartbeat interval and controls autonomic activity throughout the organism.

“It’s a mechanism that involves sensitive fibres and deformations in the walls of arteries in specific places, such as the aortic arch and carotid body. When blood pressure falls, this region warns the brain region that controls the autonomic nervous system, which in turn signals the heart to beat faster and tells the arteries to contract more strongly. If blood pressure rises, it warns the heart to beat more slowly and tells the arteries to contract less. In other words, it modulates arterial pressure beat by beat,” Brito explained.

In previous studies, the EEFE-USP research group showed that evening aerobic training reduced blood pressure more effectively than morning training in hypertensive men (read more at: agencia.fapesp.br/34194), and that the more effective response to evening training in terms of blood pressure control was accompanied by a greater reduction in systemic vascular resistance and systolic pressure variability (read more at: agencia.fapesp.br/37432).

“Replication of the results obtained in previous studies and in different groups of hypertensive patients, associated with the use of more precise techniques to evaluate the main outcomes, has strengthened our conclusion that aerobic exercise performed in the evening is more beneficial to the autonomic nervous system in patients with hypertension. This can be especially important for those with resistance to treatment with medication,” Brito said.

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Revolutionising cancer treatment: intracellular protein delivery using hybrid nanotubes

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Revolutionising cancer treatment: intracellular protein delivery using hybrid nanotubes

A new hybrid nanotube stamp system has been developed which revolutionises precision medicine with high efficiency and cell viability rates for cancer treatment.

Precision medicine and targeted therapies are gaining traction for their ability to tailor treatments to individual patients while minimising adverse effects. Conventional methods, such as gene transfer techniques, show promise in delivering therapeutic genes directly to cells to address various diseases.

However, these methods face significant drawbacks, hindering their efficacy and safety. Intracellular protein delivery offers a promising approach for developing safer, more targeted, and effective therapies. By directly transferring proteins into target cells, this method circumvents issues such as silencing during transcription and translation and the risk of undesirable mutations from DNA insertion. Additionally, intracellular protein delivery allows for precise distribution of therapeutic proteins within target cells without causing toxicity.

A group of researchers led by Professor Takeo Miyake at Waseda University, Japan in collaboration with the Mikawa Group at the RIKEN Institute have now developed a hybrid nanotube stamp system for intracellular delivery of proteins. This innovative technique enables the simultaneous delivery of diverse cargoes, including calcein dye, lactate oxidase (LOx) enzyme, and ubiquitin (UQ) protein, directly into adhesive cells for cancer treatment.

The researchers explored the therapeutic potential of delivering LOx enzyme for cancer treatment. “Through our innovative stamp system, we successfully delivered LOx into both healthy mesenchymal stem cells (MSC) and cancerous HeLa cells. While MSC cells remained unaffected, we observed significant cell death in HeLa cancer cells following LOx treatment with viabilities decreasing over time. Our findings highlight the promising efficacy of intracellularly delivered LOx in selectively targeting and killing cancer cells, while sparing healthy cells, offering a targeted therapeutic strategy for cancer treatment,” explains Miyake.

Finally, the team successfully delivered 15N isotope-labeled UQ proteins into HeLa cells using the HyNT stamp system. This delivery allowed for the analysis of complex protein structures and interactions within the cells. In addition, optical and fluorescence imaging confirmed the presence of delivered UQ in HeLa cells, and nuclear magnetic resonance spectroscopy matched the intracellular UQ protein concentration with that of a solution containing 15N-labeled UQ. These results demonstrate the effectiveness of the stamp system in delivering target proteins for subsequent analysis.

The results demonstrate the remarkable capability of the HyNT stamp system in delivering LOx and UQ into a substantial number of adhesive cells, as required for regenerative medicine applications. The system achieved a notably high delivery efficiency of 89.9%, indicating its effectiveness in transporting therapeutic proteins into the target cells with precision. Moreover, the cell viability rate of 97.1% highlights the system’s ability to maintain the health and integrity of the treated cells throughout the delivery process.

The HyNT stamp system offers transformative potential in intracellular protein delivery, with applications spanning from cancer treatment to molecular analysis. Beyond medicine, its versatility extends to agriculture and food industries, promising advancements in crop production and food product development. With precise cell manipulation and efficient delivery, the HyNT stamp system is poised to revolutionize biomedical research, clinical practice, and diverse industries, paving the way for personalized interventions and shaping the future of modern medicine.

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