Study paves the way for development of new therapeutics for C. difficile infection – News-Medical.Net

A new study paves the way for the development of next generation therapeutics for the prevention and treatment of Clostridioides difficile infection (CDI), the most frequent cause of healthcare-acquired gastrointestinal infections and death in developed countries.

Published today in Nature Communications, the study reveals the first 3D structure of the Clostridioides difficile toxin B (TcdB) in complex with chondroitin sulfate proteoglycan 4 (CSPG4), a human receptor. The study was co-led by senior author Rongsheng Jin, PhD, a professor in the Department of Physiology & Biophysics at the University of California, Irvine, School of Medicine, and Min Dong, PhD, an associate professor at Harvard Medical School.

TcdB is one of two homologous C. difficile exotoxins, which are major virulence factors responsible for the spread of C. difficile infections. TcdB alone is capable of causing the full-spectrum of diseases associated with CDI in humans."

Rongsheng Jin, PhD, Professor, Department of Physiology & Biophysics, University of California, Irvine, School of Medicine

Previous studies had identified CSPG4 as a potential receptor for TcdB, however the pathophysiological relevance and molecular details were unknown. Results from this new study reveal a unique binding site involving TcdB and CSPG4, and also show that CSPG4-binding residues are highly conserved across most TcdB variants known to date.

CDI has become the most common cause of antibiotic-associated diarrhea and gastroenteritis-associated death in developed countries, accounting for approximately 223,900 infections, 12,800 deaths, and $1 billion in healthcare costs in the United States in 2017. It is classified as one of the top five "urgent threats" by CDC. There is also growing global concern surrounding the emergence of rapidly spreading hypervirulent C. difficile strains, reminiscent of the current COVID pandemic.

"What these new findings tell us is that a rationally designed CSPG4-mimicking decoy could neutralize major TcdB variants, providing a unique therapeutic avenue for combating some of the hypervirulent C. difficile strains," said Jin. In contrast, researchers also revealed that the therapeutic mechanism for bezlotoxumab, the only FDA approved anti-TcdB antibody, is sensitive to escaping mutations in some bacterial strains.

The current standard of care for CDI involves treatments using broad spectrum antibiotics, which often lead to frequent disease recurrence. While bezlotoxumab could reduce the recurrence rate of CDI in some patients, results from this and some earlier studies indicate it has weaker potency against some TcdB variants.

"We have designed a CSPG4-mimicking decoy based on the 3D structure we observed, which could neutralize major TcdB variants and is superior to bezlotoxumab on a major TcdB variant from a hypervirulent strain (TcdB2) in our studies. As a highly conserved cellular receptor of TcdB, a CSPG4 decoy molecule would be difficult for TcdB to escape, since any mutations that disrupt toxin binding to the decoy would also disrupt binding to its native receptors," said Jin.

The team of researchers has also developed a family of recombinant protein therapeutics based on these new findings, as well as on an earlier discovery on how TcdB recognizes another human receptor Frizzled (FZD).

"We are now examining the therapeutic features of these novel antitoxin molecules, and we believe they could provide broad-spectrum protection and neutralization against most known TcdB variants, thus improving existing antibody therapeutics for CDI," said Jin, whose team has filed a patent on these neutralizing molecules.

Source:

Journal reference:

Chen, P., et al. (2021) Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection. Nature Communications. doi.org/10.1038/s41467-021-23878-3.

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Plans revealed to build world’s deepest pool, Blue Abyss, in the UK | spabusiness.com news – Spa Business

The 150m project would see an aquatic centre housing a 164ft (50m) deep pool

Primarily designed for sea and space research, the project is led by a privately-funded company, Blue Abyss

The pool will hold more than 42,000 cubic metres of water

Blue Abyss has been designed by British architect Robin Partington

The 150m project would see an aquatic centre, housing a 164ft (50m) deep pool built at the Aerohub Enterprise Zone at Cornwall Airport.

The project is led by a privately-funded company, Blue Abyss, which is now in the process of applying for planning permission.

The centrepiece of Blue Abyss will be an aquatic centre featuring a 50m by 40m stepped pool with a 50m deep shaft. The pool will hold more than 42,000 cubic metres of water the equivalent of 17 Olympic size swimming pools making it the largest and deepest indoor pool in the world.

A sliding roof and 30-tonne crane will allow large objects to be lowered into the pool, from simulated sections of the International Space Station to underwater film sets and even cave systems to test remote operated vehicles or train deep-sea divers.

With the facility, Blue Abyss wants to "revolutionise extreme environment research and training in Europe".

The centre will offer state-of-the-art whole system human physiology and human-robotic interface R&D capabilities, serving the human spaceflight, sports science and terrestrial healthcare communities.

The on-site Kuehnegger Human Performance Centre will look to cater particularly for the professional sports sector as well as healthcare with an emphasis on rehabilitation from physical deconditioning.

Blue Abyss will look to form academic partnership with national and international universities, drawing on its resources to execute R&D projects, providing a mix of expertise and facilities.

In all, the 10-acre site is set to house the pool, an astronaut training centre, the Kuehnegger Human Performance Centre, hypobaric and hyperbaric chambers, microgravity suite, training centre with six classrooms, workshops, onsite catering and accommodation facilities.

There will also be a visitor and educational centre.

Blue Abyss has been designed by British architect Robin Partington, who led the design team for The Gherkin in London.

Once open, the facility is expected to generate 8m annually for the local economy.

Blue Abyss CEO, for British Army diving instructor, John Vickers, said: "We're planning a globally unique facility with a wide range of potential uses that tap into so many of the industries that Cornwall and the South West are known for.

"Blue Abyss will be a huge research asset for aerospace, offshore energy, underwater robotics, human physiology, defence, leisure and marine industries and a fantastic education centre for children."

Other deep pools in the world include Y-40, The Deep Joy a thermal pool in Italy.

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Ohio University announces spring 2021 graduates – The Times

From Staff Reports| Beaver County Times

ATHENS, OH More than 4,800 students graduated with bachelor's, master's or doctorate degrees from Ohio University for spring semester 2021.

* Michelle Behana, of Freedom, PA, graduated with a Bachelor of Science in Nursing (Baccalaureate Nursing) from the College of Health Sciences and Professions;

* Patrick Boff, of Freedom, PA, graduated with a Master of Engineering Management from the Russ College of Engineering and Technology;

* Madeline Brown of Beaver, PA, graduated with a Bachelor of Arts majoring in anthropology and linguistics from the College of Arts and Sciences;

* Chad Cable of Aliquippa, PA, graduated with a Bachelor of Science majoring in psychology from the College of Arts and Sciences;

* Meredith Camp, of Beaver Falls, PA, graduated with a Bachelor of Science in Physiology of Exercise majoring in exercise physiology - pre-physical therapy from the College of Health Sciences and Professions;

* Devin Daley, of Conway, PA, graduated with a Bachelor of Business Administration majoring in business analytics, management information systems, and marketing from the College of Business;

* Christian Petti, of Beaver Falls, PA, graduated with a Bachelor of Business Administration majoring in marketing from the College of Business;

* Derek Weber, of Georgetown, PA, graduated with a Bachelor of Science in Engineering Technology and Management from the Russ College of Engineering and Technology.

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Bring the ‘dad jokes,’ we need ’em. (Warning: This story contains actual dad jokes) – KSL.com

Dad jokes are known to reduce tension and strengthen connections as a meta-analysis from 2017 in the journal Advances in Physiology Education examined the health benefits of humor and backs those findings. (CNN)

ATLANTA (CNN) In September 2019, just ahead of the COVID-19 pandemic so roughly before-anyone-can-remember ago Merriam-Webster added the term "dad joke" to the dictionary, to little fanfare.

As it turns out, the official addition to our vocabulary was just in time to remind us of the value of instantly available humor, especially among freaked-out family members enduring lockdowns together.

If you tell dad jokes, you already know their usefulness in reducing tension and strengthening connections. A meta-analysis from 2017 in the journal Advances in Physiology Education examined the health benefits of humor and backs those findings. Humor, the analysis found, also promotes increased learning and stress reduction. That's no joke.

"We value humor because it teaches communication, humility and happiness," articulated my brother, Matthew Henneberger, an aficionado of the dad joke. What he loves about the genre is that dad jokes introduce these great lessons to kids at a very young age.

One of my favorites I got from him: "Where does George Washington keep his armies? In his sleevies."

Dad jokes are also easy to come by, one of the low-hanging fruits of comedy. They require no setup, context or segue. They are prt--porter. You can just drop a bad pun, say something goofy or blurt out the question and punchline answer together and immediately cash in on those eyerolls and smiles.

Try this one to anyone within earshot right now: "I was going to tell a time-traveling joke, but you didn't like it."

It's that combination of groan and chuckle that defines a dad joke and also explains their appeal.

They are not all "dumb" though, even if that label is the response you get. Or maybe they are a little dumb. Smart-dumb. More Marx Brothers than Three Stooges. They are populated by puns ("Clones are people two"), one-liners ("It takes guts to be an organ donor") and malapropisms ("What does a baby computer call his father? Data.")

They are often simple and easy to grasp, but the best ones are clever, too. "What rhymes with orange? No, it doesn't."

But do you know when a joke really becomes a dad joke? When it's apparent.

And they don't have to be just for kids, despite the name. But they must be G-rated. Dad jokes don't do blue or offensive. You can always safely tell a dad joke in front of kids, but depending on their age, you may need to explain why it's funny (in a very dadlike fashion).

Take this Zen koanlike gem: "What did Buddha say to the hot dog vendor? Make me one with everything." A worldly 10-year-old may get that one along with most adults, less so little kids.

And given their liberal use of homonyms, these jokes are often better delivered in person, like this one: "Did you hear about the circus fire? It was intense (in tents)."

My CNN colleague Alberto Mier likes to misuse his kids' slang or purposely bungle the names of things they like ("The Tickity Tock," for example).

"My 16-year-old, in particular hates it, so I do it even more," he added. "Stupid, but it drives her nuts, and that's what it's all about."

Basically, dad jokes are just fun. And we need more fun. It's also why we invited the mushroom to the party because they are the fungi!

So, collect them, memorize them, and start dropping them on others. I have a Google doc of favorites I've stumbled across or were told to me by fellow dads (and moms), like this winner from fellow dad and friend Sam Younis: "Why did the old man fall in the well? He couldn't see that well."

During the pandemic, Younis bought a book of dad jokes ("The Little Book of Dad Jokes: So Bad They're Good"). He keeps it handy in the kitchen just to lighten the mood.

"Now my kids read the jokes to me and shake their heads when they see me laugh," he said.

When you hear or read them, curate your favorites. I picked up this science dad joke from a CNN interview with Neil deGrasse Tyson: "Why can't you trust an atom? Because they make up everything."

So, curate your list (in a "dad-a-base!") and start busting them out. Fill the awkward wait at the start of a meeting, make your kid and their friends crack up (or enjoy their bonding over shared eye-rolling), and do it maybe the chief reason to delight yourself.

All right, ready for more jokes? CNN's Dad Joke Generator has your fix.

Time for me to make like a tree and leaf.

The-CNN-Wire & 2021 Cable News Network, Inc., a Time Warner Company. All rights reserved.

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PET/CT Effective Measures NSCLC Biomarker, Predicts Therapy Response – Diagnostic Imaging

PET/CT images can non-invasively measure levels of a non-small cell lung cancer (NSCLC) biomarker, eliminating the need for biopsy and predicting the patients response to therapy.

Checkpoint inhibitors that target the PD1/PD-L1 signaling pathway are an effective treatment for NSCLC, but it only works in roughly half of patients. Investigators from Moffitt Cancer Center demonstrated, in a study published this week in the Journal for ImmunoTherapy of Cancer, that PET/CT can effectively assess the patients PD-L1 level, helping patients and providers to side-step the risks that come with invasive biopsy.

This study is important, as it is the single largest multi-institutional radiomic study population of NSCLC patients to date treated with immunotherapy to predict PD-L1 status and subsequent treatment response using PET/CT scans, said Robert Gillies, Ph.D., chair of Moffitts cancer physiology department. Because images are routinely obtained and are not subject to sampling bias per se, we propose that the individualized risk assessment information provided by these analyses may be useful as a future clinical decision support tool pending larger prospective trials.

For their study, the team examined PET/CT scans for nearly 700 patients who had NSCLC who were treated in three institutions. They assessed shape, size, pixel intensity, and textures to train a deep learning tool to accurately measure PD-L1 expression. Using the data, they developed a deep learning score that could predict PD-L1 expression which, after validation, could predict checkpoint inhibitor outcomes in these patients.

Their results point to the usefulness of using images as a replacement for biopsy, said Matthew Schabath, Ph.D., associate member of the cancer epidemiology department.

These data demonstrate the feasibility of using an alternative non-invasive approach to predict expression of PD-L1, he said. This approach could help physicians determine optimum treatment strategies for their patients, especially when tissue samples are not available or when common testing approaches for PD-L1 fail.

For more coverage based on industry expert insights and research, subscribe to the Diagnostic Imaging e-Newsletterhere.

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Study Explored Benefits of Yoga in Chronic Low Back Pain – India Education Diary

Most of the yoga-based studies so far have relied on patients experience and rating of pain and disability as an indicator of recovery and better quality of life. Researchers who measured pain, pain tolerance and body flexibility have found that yoga leads to pain relief, increases tolerance of pain and improves flexibility in patients of chronic low back pain.

Dr Renu Bhatia, Additional Professor, Department of Physiology, AIIMS, New Delhi conducted research to measure the impact of yoga on Chronic Low Back Pain (CLBP) along with Dr Raj Kumar Yadav (Professor, Department of Physiology, AIIMS, New Delhi), Dr Sri Kumar V (Associate Professor, Department of Physical Medicine & Rehabilitation, AIIMS, New Delhi).

The study conducted on 100 Chronic Low Back Pain (CLBP) patients of 50 years with 3 years of history of the disease. After systematic Yogic intervention of 4 weeks, Quantitative sensory testing (QST) showed increase in thresholds for cold pain and cold pain tolerance. Corticomotor excitability and flexibility improved significantly in the patients.

They recorded objective measures for pain (electrophysiology), sensory perception (quantitative computerized sensory testing) and cortical excitability parameters. (using Transcranial Magnetic Stimulation of motor cortex).They found significant changes between all the parameters in CLBP patients compared to healthy controls at baseline. Significant improvement in all parameters was found after yoga.

This research supported by the Science and Technology of Yoga and Meditation (SATYAM) funded by the Department of Science and Technology, GoI has been recently published in theJournal of Medical Science and Clinical Research.

Assessment of pain and corticomotor excitability parameters shall help in establishing strong ground with scientific evidence for yoga to be prescribed as therapeutic intervention for chronic low back pain relief with or without standard therapy depending on the pathology. Also these parameters can be used for prognosis and follow-up of patients during recovery phase.

The team also developed yoga protocol for CLBP patients and for fibromyalgia patientsin Pain Research and TMS laboratory, AIIMS, New Delhi.

In patients with Chronic Low Back Pain, 4 weeks of yoga intervention improved pain status and pain-related functional disability, increased spinal flexibility and corticomotor excitability significantly more than standard care.

The study suggests that in long term Yoga can be performed at home, and hence is an inexpensive therapeutic intervention. It not only relieves pain but also improves overall quality of life and bestows other health benefits.

Dr. Renu Bhatia

Publication link:https://dx.doi.org/10.18535/jmscr/v9i3.30

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Ocean warming could hit shark survival – The University of Manchester

Infant sharks that live in the familiar mermaids purses found on most beaches in the UK and throughout the world are more vulnerable to predation because of ocean warming, new research suggests.

According to Daniel Ripley from The University of Manchester, higher temperatures reduce freeze response times which the animals employ to avoid being eaten by predators.

The study by the ecophysiologist is funded by the Biotechnology and Biological Sciences Research Council and The University of Manchesters Knowledge and Innovation hub for Environmental stability

It is published in the Journal of Conservation Physiology today (17 June).

If an embryo employs a freeze response, it stops moving so that predators - including large fish and other sharks - wont detect them.

That explains why being able to elicit a freeze response is key to surviving predation during embryonic development and the longer an embryo can freeze, the better chance it has of not being detected by predators.

In the lab Ripley compared the freeze response time of small spotted catshark embryos - which are 7 to 8cm long - at a water temperature of 15C and a water temperature of 20C.

The 5C temperature rise resulted in a 7-fold decrease in the time the animals froze following a predator simuli, mimicked by gently flicking the egg case

And that could have major consequences for embryonic sharks in a warming world. Being able to freeze is key to avoiding predators and if warming means infant sharks will not be able to freeze as long, it could reduce the number of sharks surviving to adulthood.

Around 45% of shark and ray species lay eggs which grow inside a mermaids purse, which can last for around a year before they hatch

The purses come in various colours, shapes and textures, depending on the species of shark.

Beachcombers often spot the empty shell cases on the beach, though the live egg cases often lie tangled up with sea weed in shallow waters and rockpools.

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Ocean warming could hit shark survival - The University of Manchester

Neuroscience (and a Tiny Dose of Emotional Intelligence) Reveals the Simple Trick to Break Nearly Any Bad Habit – Inc.

Nice piece of grilled salmon. Brown rice. Salad with no dressing. I feltfull: Not stuffed, but satisfied. Better yet,I felt good about having eaten a healthy meal.Then the ice cream called me.

Think you make a lot of decisions? You do, but not as many as you think.Research shows that approximately 40 percent of the things we do on a daily basis aren't decision-based. They're habits.

And someare bad habits.

Which doesn't, at first glance, make sense."We find patterns of behavior that allow us to reach goals," says Dr. Wendy Wood, the author of Good Habits, Bad Habits."We repeat what works, and when actions are repeated in a stable context, we form associations between cues and response."

So why do we form habits that don't help us reach our goals? My goal is to maintain a healthy weight, and eating ice cream is a far fromsupportivepattern of behavior.

Because neuroscience -- theway our brains are made -- oftenworks against us. (H/t to Eric Barker for the underlying science.)

Say I ask myself, "Should I have some ice cream?" My prefrontal cortex -- thebrain region responsible forplanning,decision making,and supporting goal-oriented behaviors-- would answer, "Nope. Your goal is to eat healthy."

Except my orbitofrontal cortex -- the brain region responsible for emotion and reward in decision-making -- would answer, "Dude, you absolutely should! Ice cream is awesome. You love it. It makes you happy. Besides, you can always burn the calories off by working out a little extra tomorrow..."

Because while my prefrontal cortexis alogical and rational kind of guy, he's fairly quiet and subdued. My orbitofrontal cortex? He's a yeller. He's insistent. He loves to get his way.

And he loves to create bad habits.

Or, as Dr. Wood explains inneuroscientificterms, "When our intentional mind is engaged, we act in ways that meet an outcome we desire -- and typically we're aware of our intentions. However, when the habitual mind is engaged, our habits function largely outside of awareness. We can't easily articulate how we do our habits or why we do them...our minds don't always integrate in the best way possible."

In short, give my orbitofrontal cortexa chance and I'll quickly establish some bad habits. I'll do things reflexively, almostwithout thinking.

If I do manage to think, "Wait, should I really have ice cream...?" that little voice in my head getsdrowned out by my orbitofrontal cortex and the force of habit.

And yep, I'm screwed. Now my goal isn't to achieve something positive by repeatingwhat works. My goal is just to satisfy my habit of eating ice cream. So I do. Without really thinking.

Because if I thought about it, I wouldn't be likely to do it.

As Dr. Wood says, "Habits allow us to focus on other things. Willpower is a limited resource, and when it runs out, you fall back on habits." (If you're like me, you can almost feel a switch flipping in your mind that instantly shuts off any rational thoughts.)

So how do you break that cycle?

The answer is simple, yet difficult: You have to force yourself to think: Not before, but during.

Not, in my case,not before I eatthe ice cream -- because that requires willpower I clearly don't have -- but while I'm eating the ice cream.

The key is to reflectupon the actual benefits derivedfroma habit. For me? Ice cream tastes good. Ice cream... well, that's pretty much the list.It don't feel healthier. I don't feel better when I'm finished. In fact, I feel worse;maybe not physically, but definitelyemotionally.

One upside,lotsof downsides.

And then repeat the process, because one period of reflection and introspection won't be enough. I'll probably have to do it several times before it sinks in -- before my orbitofrontal cortex adopts the rewards and emotions involved in not feeling badabout eating ice cream andnot feeling like I'm sabotaging my health and fitness goals.

Then those two voices will speak in unison. My prefrontal cortexwill share all the long-term benefits ofeating healthy. My orbitofrontal cortex will chime in withreasons why skipping theice cream willmakeme feel better in the moment. In emotionalintelligence terms, myemotions will work for me, not against me.

And that's how the habit gets broken.

Try it. Say, like my Inc. colleague Justin Bariso, you want to stop watching YouTube videos when you know you should be working. The next time the urge strikes, don't fight it. Watch a video.

But don't do it mindlessly: Think about what you're watching. Is it entertaining? Do you gain any value from it? Is it more fun -- or more rewarding or fulfilling or satisfying --than doing something else?

What do you really get out of it?

Do that enough times, reflect on the actual feelings and benefits that result from a habit, and in time you'll start to make a different choice.

Because then yourintentional and habitual minds won't have to work againsteach other.

They'll be able to work together.

The opinions expressed here by Inc.com columnists are their own, not those of Inc.com.

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Norton Healthcare to open comprehensive neuroscience facility – Norton Healthcare

On June 17, Norton Healthcare will open a comprehensive neuroscience facility unlike any other in the region. This new facility will benefit patients and the community by providing a comprehensive, multidisciplinary neurosciences program with leading-edge technologies and enhanced research and outreach efforts.

The Norton Neuroscience Institute space, located in Norton Medical Plaza III on the Norton Brownsboro Hospital campus, will support patients with many types of neurological conditions, including brain, spinal and nervous system tumors; stroke; epilepsy; migraine and headache; dementia; and memory care. It also will be home to Norton Neuroscience Institutes Cressman Parkinsons & Movement Disorders Center and Cressman Neurological Rehabilitation, as well as a pain management clinic.

The new space encompasses more than 48,000 square feet of clinical, diagnostic, procedural and rehabilitation space. It contains advanced equipment to allow patients to undergo complex neurological testing and procedures at the same site as their routine office visits. Norton Healthcare invested $15 million into the project.

Neuroscience treatment is rapidly evolving, and were committed to bringing the best care to patients throughout this community, said Russell F. Cox, president and CEO, Norton Healthcare. With this location, patients will be able to receive compassionate, specialized care with the newest technology and equipment, all in one convenient location. This space is designed not only to address patients needs but also to aid in the comfort and ease of their care and recovery.

Many neurological conditions require treatment by multiple providers. Having a centralized location will allow the team to more easily collaborate to develop individualized courses of treatment. Located next to Norton Brownsboro Hospitals Comprehensive Stroke Center and Level 4 epilepsy center, the space also will improve access to follow-up care after patients leave the hospital.

Having dedicated space for comprehensive neurological care and rehabilitation will make it much easier for us to convene in person and develop customized treatments for each patient, said David A. Sun, M.D., Ph.D., neurosurgeon and executive medical director, Norton Neuroscience Institute. We believe this level of collaboration sets us apart from other neuroscience centers.

The new Cressman Neurological Rehabilitation space is equipped with the latest rehab technology, including a virtual reality balance assessment system, a driving simulator, robotic-assisted therapy and more, which will help patients recover and develop skills to live independently. It was made possible thanks to a $616,000 grant from the Norton Healthcare Foundation.

More than a decade ago, Norton Healthcare invested $100 million and created a vision to build one of the best neuroscience programs in the country, and this facility will help us realize that goal, said Lynnie Meyer, Ed.D., R.N., CFRE, senior vice president and chief development officer, Norton Healthcare. The Norton Healthcare Foundation has provided millions of dollars in funding to Norton Neuroscience Institute for Cressman Parkinsons & Movement Disorders Center, memory care, and other vital programs. We look forward to continuing to support their impactful work for years to come.

Classes currently offered through the Norton Neuroscience Institute Resource Center, such as tai chi, yoga, Lego therapy and patient support groups, will be offered at the new facility. These programs have been held virtually during the pandemic, but the goal is to go back to in-person classes in the near future.

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WVU Rockefeller Neuroscience Institute first in region, among first in US to offer latest deep brain stimulation technology for patients with…

WVU Rockefeller Neuroscience Institute first in region, among first in US to offer latest deep brain stimulation technology for patients with Parkinson's  WVU Medicine

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WVU Rockefeller Neuroscience Institute first in region, among first in US to offer latest deep brain stimulation technology for patients with...