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Astrocytes identified as master ‘conductors’ of the brain

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In the orchestra of the brain, the firing of each neuron is controlled by two notes – excitatory and inhibitory – that come from two distinct forms of a cellular structure called synapses.

Synapses are essentially the connections between neurons, transmitting information from one cell to the other. The synaptic harmonies come together to create the most exquisite music–at least most of the time.

When the music becomes discordant and a person is diagnosed with a brain disease, scientists typically look to the synapses between neurons to determine what went wrong. But a new study from Duke University neuroscientists suggests that it would be more useful to look at the white-gloved conductor of the orchestra – the astrocyte.

Astrocytes are star-shaped cells that form the glue-like framework of the brain. They are one kind of cell called glia, which is Greek for “glue.” Previously found to be involved in controlling excitatory synapses, a team of Duke scientists also found that astrocytes are involved in regulating inhibitory synapses by binding to neurons through an adhesion molecule called NrCAM. The astrocytes reach out thin, fine tentacles to the inhibitory synapse, and when they touch, the adhesion is formed by NrCAM. Their findings were published in Nature on November 11.

“We really discovered that the astrocytes are the conductors that orchestrate the notes that make up the music of the brain,” said Scott Soderling, PhD, chair of the Department of Cell Biology in the School of Medicine and senior author on the paper.

Excitatory synapses — the brain’s accelerator — and inhibitory synapses — the brain’s brakes — were previously thought to be the most important instruments in the brain. Too much excitation can lead to epilepsy, too much inhibition can lead to schizophrenia, and an imbalance either way can lead to autism.

However, this study shows that astrocytes are running the show in overall brain function, and could be important targets for brain therapies, said co-senior author Cagla Eroglu, PhD, associate professor of cell biology and neurobiology in the School of Medicine. Eroglu is a world expert in astrocytes and her lab discovered how astrocytes send their tentacles and connect to synapses in 2017.

“A lot of the time, studies that investigate molecular aspects of brain development and disease study gene function or molecular function in neurons, or they only consider neurons to be the primary cells that are affected,” said Eroglu. “However, here we were able to show that by simply changing the interaction between astrocytes and neurons — specifically by manipulating the astrocytes — we were able to dramatically alter the wiring of the neurons as well.”

Soderling and Eroglu collaborate often scientifically, and they hashed out the plan for the project over coffee and pastries. The plan was to apply a proteomic method developed in Soderling’s lab that was further developed by his postdoctoral associate Tetsuya Takano, who is the paper’s lead author.

Takano designed a new method that allowed scientists to use a virus to insert an enzyme into the brain of a mouse that labeled the proteins connecting astrocytes and neurons. Once tagged with this label, the scientists could pluck the tagged proteins from the brain tissue and use Duke’s mass spectrometry facility to identify the adhesion molecule NrCAM.

Then, Takano teamed up with Katie Baldwin, a postdoctoral associate in Eroglu’s lab, to run assays to determine how the adhesion molecule NrCAM plays a role in the connection between astrocyte and inhibitory synapses. Together the labs discovered NrCAM was a missing link that controlled how astrocytes influence inhibitory synapses, demonstrating they influence all of the ‘notes’ of the brain.

“We were very lucky that we had really cooperative team members,” said Eroglu. “They worked very hard and they were open to crazy ideas. I would call this a crazy idea.”

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Carers at risk of being forgotten

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A study has found that 68% of people believe they should ‘reach out’ to carers more often – with 60% of respondents only asking carers how they are ‘now and again’, ‘rarely’ or ‘almost never’; leaving carers at risk of feeling forgotten.

Furthermore, 72% of respondents worried that carers struggled with ‘loneliness’ thanks to the full-on nature of care leaving them little time for socialising.

Throughout the pandemic, caregivers have been at the forefront of the fight, looking after the most vulnerable in society and putting their own lives on the line to do so. In light of this, a campaign called #ReachOutAndHelpOut has been launched to encourage support for carers as they continue to deliver essential care to those in need – amidst fears that carers’ wellbeing is often overlooked.

Spearheaded by Sentai, a British technology start-up focused on helping the elderly live more independently in their own homes, the campaign looks to highlight the vital role that carers play.

Respondents, mindful of the associated health impact of winter, believe the biggest fears to be faced by carers in coming months is another ‘national lockdown’ (60%), while 53% of respondents saw ‘excessive workload’ as a primary worry. 50% also believed ‘difficulty visiting family and friends due to their care commitments’ was a central concern, while ‘juggling different responsibilities’ was a key issue according to 46%.

Other concerns included ‘lack of time’ (32.9%) and carers ‘feeling they’re not doing enough’ (25%).

Professor Ray Jones, professor of health informatics at Plymouth University and director of eHealth Productivity and Innovation in Cornwall and the Isles of Scilly (EPIC), which focuses on the provision of internet based healthcare services (eHealth) voiced his support for the campaign, highlighting the difficulties carers face.

He said: “The impact of the coronavirus crisis has been profound on almost all aspects of society. For carers though, this impact has been magnified to a far higher degree. The physical and psychological toll of caring during a pandemic is huge. We must be mindful of the burden placed on carers and do what we can to help. The service they provide is essential, and we’re all indebted to their hard work. The very least we can do then is simply ask them how they’re doing and offer whatever assistance we’re able to give.”

These sentiments were echoed by Philip Marshman, founder of Sentai and orchestrator of #ReachOutAndHelpOut, who said: “The role of a carer is often overlooked. It’s all too easy to ask how the recipient of care is without extending that concern beyond to take into account the person looking after them. Carers are people, not robots, and now, more than ever we must do what we can to consider and support their wellbeing and mental health.”

Sentai has launched a Kickstarter campaign to raise funds for the next stage of its smart device development, the success of which will see its pioneering technology brought to mass market – allowing those in need to benefit from its advanced offering.

Philip said: “The experience of looking after my own father led me to create Sentai, and it’s been developed to help both the care recipient and the caregiver. Through revolutionary voice technology it initiates intelligent conversations, helping to alleviate boredom and loneliness, while also providing helpful reminders. It’s safety properties also allow the caregiver to monitor the care recipient remotely and unobtrusively, providing reassurance that the care recipient is OK and acting as normal, thereby helping to ease stress and worry for the caregiver.”

He added: “We have everything in place to deliver a successful solution – we want to get Sentai into people’s homes as quickly as possible – whether that’s someone’s own home, or a care home. Raising funds in this way means we can stay true to our mission which is helping people live more independently, for longer.”

Further details of the Kickstarter campaign can be found via https://www.kickstarter.com/projects/sentai/sentai.

To find out more about the #ReachOutAndHelpOut campaign and the different ways to get involved, including the chance to win a well-deserved break away, please visit sentai.ai/ReachOut.

Others in the care industry who have expressed support for the #ReachOutAndHelpOut campaign, include Dr Stephen Ladyman, founder of Oak Retirement and former Minister of Health responsible for Social Care, and Shaleeza Hasham, founder of the Adopt a Grandparent scheme and head of hospitality at care home and home care provider, CHD Living.

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PhysioFunction setting the trend for telerehab

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Having been an early adopter of telerehab, PhysioFunction was perhaps less daunted than most at the prospect of responding to the COVID-19 lockdown and ensuring their clients’ needs were met.

The specialist neuro physiotherapy practice has, for the past year, used video calls to enable its clients to receive one-to-one sessions in addition to those provided in person, with its staff supporting them to install and use the technology remotely.

It is also an early adopter of the MindMotion GO, a first-of-its-kind mobile neurorehabilitation therapy system which uses gaming to support the recovery of brain injury and neuro patients.

PhysioFunction has reported strong levels of engagement and progress among clients as a result of its telerehab programme, which has increased in its use during the past few months amidst the pandemic.

From its specialist outpatient rehabilitation unit in Northampton, PhysioFunction supports patients from a 100-mile radius, which was a key driver in the adoption of virtual means of delivering therapy.

Claire Everett, clinical operations manager at PhysioFunction and a senior neurological physiotherapist, said: “For some time now, we have tried to embrace the use of online means for therapy, and it has really helped many of our clients. By doing sessions in their own homes, we see them taking ownership of their rehabilitation and it delivers benefits to them in their own settings.

“For example, we might be doing a session by video with a client on how to cope in the kitchen – but because it’s their own kitchen they’re in, that makes it even more relatable.

“It is a very useful way for some clients who perhaps struggle to get to us once a week, but cope much better with two half-hour weekly sessions by telerehab. We do carry out home visits, and will combine the remote sessions with hands-on therapy wherever we can, but some clients live quite a distance away or maybe it isn’t easy for them to get out of the house.

“By holding sessions by video, it doesn’t matter where they live, whether it’s round the corner or two hours away, and we’ve had a great response to our telerehab work. It’s changed our practice in some really positive ways.”

When lockdown came, while for many organisations a swift and seismic move to the adoption of remote communication was needed, PhysioFunction were in the enviable position of being able to build on what they had already created.

“With us already being established with many clients, we didn’t have to start from scratch, and we could look at how to build on what we had already done. By extending our telerehab programme, we could continue to support our clients effectively,” says Claire.

“The team were able to take our classes online from a very early stage, with Taher Dhuliawala and Keiran Cox very much holding the fort during lockdown. The classes followed the same format as in person, with small numbers of participants so we can easily spot if someone needs help, but we were able to increase the frequency of them. Being able to do these kinds of sessions in your own living room was really welcomed.

“With clients who were already able to use video, we also were able to introduce the MindMotion GO, which is fantastic as we can interact with the technology and, for example, increase the intensity as required. But at the start of the pandemic, we still had some clients who didn’t use video, and the fact we have supported them to use it meant they had an extra channel of communication with their family during lockdown, and that was a lovely extra benefit.

“Even aside from COVID, with the flu and winter weather coming, we are expecting further demand for our telerehab sessions. We’re currently running a blended approach of online and in-person sessions, although a few people are still choosing not to come in at all, but they have found our telerehab so effective that they’re still progressing with their therapy.”

While remote working was a ‘needs must’ for many practices during lockdown, and to help mitigate ongoing restrictions, PhysioFunction intend to continue to build telerehab as a core function.

“We are very into innovation and technology here and our team have worked really hard to do what we’ve done, I’m really proud of what we’ve achieved,” adds Claire.

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The psychiatrist fighting for domestic violence victims

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Australia’s New South Wales government has promised to improve brain injury testing for domestic abuse victims after a psychiatrist drew attention to inconsistent care for vulnerable women. Psychiatrist Karen Williams urged the government to adopt a concussion protocol for family and domestic violence victims after doing her own research and being shocked at what she found.

It started when Williams noticed the disparity in how her patients were diagnosed and treated.Williams specialises in the treatment of post-traumatic stress disorders (PTSD), often with military, police, emergency personnel and other first responders.

But she also treats the general population, the vast majority of whom are women with histories of child and domestic abuse.

“I was getting two populations,” she tells NR Times. “The military patients, who are clearly identified as having PTSD, and the female population, who are mostly identified as having depression, anxiety and personality disorders, but had incredibly high rates of abuse in their histories.But Williams saw that whilst both groups had similar symptoms, and similar levels of trauma, they had very different treatment options.

“There’s a lot more funding put into supporting traumatised soldiers and first responders than there is for women who have experienced trauma within their home.

“In Australia, we don’t have much at all for women and children victims of abuse.”

This was a particular concern because of the amount of times Williams had heard about multiple head injuries and concussion among women who were victims of domestic abuse, which is similar to boxers and those player high contact sports.

“Women who’ve been unconscious several times or strangled have symptoms such as memory deficits, insomnia, migraine and mood swings, which all could be put down to PTSD and depression, but also brain injuries.”

But if Williams wanted to find out if a patient had a history of brain injuries, she would have to refer them for neuropsychiatric testing, which costs up to AUS$1000.

“This is completely unaffordable for many abuse victims so it just doesn’t happen, so we don’t investigate women who’ve had brain injuries.

“One brain injury unit told me they would consider taking on a patient if they could provide evidence that an assault happened – such as hospital records.

“This completely fails to take into account that the vast majority of domestic violence survivors will not report any assault to anyone and will not have so-called evidence.”

Then, Williams was speaking to a colleague whose son had had a head injury in a sporting field.

While they were together, a nurse rang to follow up the treatment he’d received in the emergency department.

“The nurse asked how her son’s personality and memory was, and gave a fantastic run-down of the symptoms that can happen after a concussion,” Williams says.

Williams was shocked – she’d never heard of someone ringing up women after a head injury in a domestic violence case.

She rang the local emergency department and asked about their protocol following a head injury obtained during sport.

She was given a detailed outline of the observations they take, their plan over the weeks following the patient’s injury and the advice they give the patient.

Williams called several emergency departments in other Australian states, and whilst all had a protocol for sports players following a concussion, none said they had a protocol for women who had been the victim of domestic abuse.

“There wasn’t one place that said they had a particular protocol.

“If they knew the woman had had a head injury they’d give them the basic head injury protocol, but nothing specific that took into account the very individual needs that a woman with a head injury in a domestic situation might have,” she says.

Williams says research indicates health care professionals correctly identify family violence victims about one per cent of the time.

“In sporting players’ protocol, there’s a recognition that says that your patient may not know what they’ve experienced in the past was a head injury, so the advice is to be really explicit. They’re given a list of questions to break it down with that player to make sure they understand what could be a head injury.

“There is opportunity for scanning, and neuropsychological testing if there is evidence of persistent symptoms.”

Williams says doctors should be going through the history of women, too, to see if they’ve lost consciousness in the past.

“There are a variety of mechanisms in which a woman experiences brain injuries in a domestic situation, many more than sporting probably, and the more head injuries a woman has, the greater her chance of long-term problems,” Williams says.

This includes a higher risk dementia, PTSD, migraines, learning problems and memory problems.

“But women aren’t told this, so many don’t know that they’re at risk of these things.”

Williams says there is a ’hidden epidemic’ of women in the community with brain injuries no one knows about, who could have been diagnosed with mental health issues instead.

In 2018, Brain Injury Australia released its findings after looking at the prevalence of brain injury in victims of domestic violence.

It found that 40 per cent of victims who attended hospitals in Victoria, Australia, for domestic violence had a brain injury and the majority were women.

But there’s no specific treatment for these women, Williams says, and many won’t even know they have a brain injury.

“Abused women are a very neglected population, and when you think about the money being spent on sports, and sports players, there’s no reason we can’t look after woman as well,” Williams says.

But despite these findings, Williams says it didn’t lead to any change.

“When I found all this out, I was angry and upset,” Williams says.

She arranged to meet New South Wales’s Labour MP Anna Watson in August, and when Williams told her what she’d found, she says Watson was ‘mortified’.

“She immediately got on the phone with the office of the minister for the prevention of domestic violence, and requested a meeting as soon as possible.

In the Zoom meeting a month later, Williams went over what she had found with Mark Speakman, Attorney General and Minister for the Prevention of Domestic Violence, and outlined the obstacles facing women.

But he made no promises, and Williams said she felt he didn’t understand the urgency or gravity of the situation.

Watson then went to the media, and the story was reported on. Within a week, the government produced a statement promising to investigate the issue.

“We’ll all be watching and holding them accountable,” Williams says.

“I will be trying to follow up, I won’t let it go.”

Williams is disheartened that it took media coverage to get the government to respond, but says she’s learnt a valuable lesson.

“Part of the reason I’ve spoken to the media and been vocal about it, is my experience is that when we do things quietly and ask for things politely, the government says there’s no money, despite being one of the wealthiest countries in the world. But when the voting population starts getting angry and asking what’s going on, that’s when we see an answer.

“It’s been a sad realisation for me to recognise that people don’t respond to do the right thing, they respond to winning the vote, so I will keep being as loud as possible in the media.”

Leaving brain injuries undiagnosed has significant consequences, Williams says.

“You’ve got women feeling like they’re a bit crazy, women wondering, ‘Why don’t I remember things, why have I got headaches all the time, why can’t I sleep?’

“It makes women feel worse, like something is wrong with them rather than identifying the underlying cause that we’re completely missing.

“If women are unable to work due to the physical and psychological side effects of a recurrent head injury, they need to be able to apply for NDIS funding (National Disability Insurance Agency). f they don’t know they have a brain injury they will be left to flounder – which is what is happening now.

“The vast majority of doctors don’t know about this. The medical system failing these women.”

There will be a lot to work out as support becomes available, Williams says, as some women could fear that having brain injury diagnosis could interfere with them getting custody of their children.

But, ultimately, change will benefit these women.

“All women deserve to know the truth about what’s happening to them,” she says.

“In some cases, their brain injury will be the final straw. They might think an act of violence isn’t a big deal, but if a doctor says, ‘Look how many times this has happened to you, you could end up long term brain damage’, that might be the final push that makes her take steps to leave. There’s no excuses to justify why these conversations aren’t had.”

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