Connect with us

Bioengineer

Repetitive compression of limbs appears to aid recovery from deadly brain bleeds

Avatar

Published

on

IMAGE

Credit: Kim Ratliff, Augusta University photographer

AUGUSTA, Ga. (Feb. 25, 2021) – Scientists want to know more about how an inexpensive, low-risk treatment may improve recovery from the most deadly type of stroke.

The treatment, remote ischemic conditioning, or RIC, involves successive bouts of compressing then relaxing an arm or leg with a blood pressure-like cuff, most typically for four cycles of five minutes of inflation followed by five minutes of deflation.

The most deadly stroke is an intracerebral hemorrhage, the most common form of hemorrhagic stroke, in which blood, which is toxic to brain tissue, spills out of blood vessels in the brain.

“When you look at this type of stroke on imaging you will have the blood there, taking up space, and then it just starts killing the tissue off within that area,” says Dr. Krishnan Dhandapani, neuroscientist in the Department of Neurosurgery at the Medical College of Georgia at Augusta University.

To aid recovery and survival, the spilled blood and already damaged brain tissue need to be promptly removed and new blood vessel networks laid down to properly restore blood and oxygen, as well as deliver healing trophic factors and nutrients to the damage site. The MCG scientists have laboratory evidence that RIC, already in clinical trials in several countries, helps.

Dhandapani is principal investigator on a new $1.9 million grant (RO1NS117565) from the National Institutes of Health that is enabling him and his colleagues to learn more about how RIC helps, and how long the treatment is needed to provide optimal benefit.

They have evidence that RIC enables better use of a natural pathway for brain repair, much as immunotherapy for cancer augments the body’s natural defense mechanisms.

“We are trying to accelerate functional recovery,” Dhandapani says. “RIC may just be hijacking the spontaneous mechanisms and making everything go faster.”

A consistent they have seen in their studies is improved blood flow to the brain and a shift toward an anti-inflammatory state, across not just hemorrhagic strokes, but the more common ischemic strokes, where a blood clot inside a blood vessel is the problem, and traumatic brain injuries as well.

In addition to location, all three have in common that while inflammation is important to healing early on, ongoing inflammation contributes to brain damage.

Potential theories about how RIC reduces damage include that the transient bouts of ischemia from compression of the arm or leg signal the brain, always the body’s first priority for blood and oxygen, that it needs to make adjustments. “It’s a controlled tourniquet really,” says Dhandapani. “But we don’t know the exact mechanism.”

Co-investigator and research scientist in the MCG Department of Neurology Dr. M.B. Khan says the benefits of RIC and exercise overlap, because exercise also increases the need for oxygen and activates factors that can help like the powerful blood vessel dilator nitric oxide. “This is a nonphysical mimetic of exercise,” adds Dhandapani. Like exercise, they say RIC may need to be continued to continue to see benefit.

Since RIC increases blood flow, the approach seemed counterintuitive at first in hemorrhagic stroke where it might increase bleeding, the scientists say. Instead: “It just opens the highway,” Dhandapani says of the resulting reparative shifts.

They suspect one way RIC improves blood flow is by creating shear stress as red blood cells are forced to squeeze through a narrower passageway. Shear stress is detected by the endothelial cells that line blood vessels which send paracrine signals, proteins synthesized by one cell that act on nearby cells to change their behavior, which in this case are telling neighboring smooth muscle cells inside the blood vessel wall to relax and let more blood through.

They have evidence RIC also prompts a shift away from the inflammatory environment needed right after injury, to an anti-inflammatory environ important to recovery. In fact, RIC’s impact does not appear to be immediate, rather after about the third day, clots start shrinking much faster in lab animals receiving RIC than in those who don’t, findings which Dhandapani and his colleagues have published. A key difference in the shift is the macrophages, a type of immune cell known for scarfing up debris, but that can also help turn inflammation both up or down. While macrophages keep cleaning after RIC, the scientists have found that they stop promoting inflammation, another of their published findings and a basis for some of the clinical trials of RIC now underway, Dhandapani says.

With this grant, they are further exploring these reparative macrophages to see what they are doing not just in the early days to help shrink the clot, but over six months, and whether, as they suspect, ongoing RIC is necessary to maintain whatever good they do. Khan has already conditioned a mouse model of dementia daily for six months and seen continued improvement. Now they are looking at both the timing for starting and continuing RIC for hemorrhagic stroke.

“We want to see if RIC kind of helps rebuild the brain,” Dhandapani says. “Is there anything that is reparative in the long term,” he says, which takes him back to opening the highway.

They have seen new blood vessel growth in aftermath of stroke and RIC in brain areas essentially wiped out by stroke, and think that the reparative macrophages may be helping with that longer term.

Now they are testing their hypothesis that the transient ischemia RIC induces in turn induces AMPKα1, a sensor and regulator of energy metabolism, and Del-1, a protein with an important role in blood vessel remodeling and development, to help restore the essential vascular network. They are doing things like knocking Del-1 out of mice to see if RIC’s benefit disappears along with the protein. If it does, they want to start measuring Del-1 levels in people using RIC to see if the protein’s level also increases in humans.

While RIC is not a “be all, end all,” it appears to help rebuild a viable infrastructure for viable brain tissue to once again exist in that area, with additional therapies down the road like stem cell therapy to regenerate neurons that will ultimately connect and restore networks and functions lost to stroke, Dhandapani says. “It’s a better microenvironment for regenerating neurons,” he says.

“You have to clear all the rubble if you want to build a new building. We think that is what macrophages are doing very early. We think step 2 is rebuilding the framework and structure,” he says.

RIC is one of a handful of potential new stroke therapies being compared in the National Institutes of Health initiative Stroke Preclinical Assessment Network, or SPAN, evaluating treatments with promise. Large studies using RIC in patients with stroke also are underway in Denmark and China and its being studied in dementia patients in Greece.

About 87% of strokes are ischemic where a blood clot impairs blood flow. With hemorrhagic strokes, typically a weak blood vessel inside the brain ruptures, which can form a large pool of blood, called a hematoma, in the brain tissue itself and blood, as well as the iron inside the red blood cells that carry oxygen, are highly lethal to brain tissue, especially the neurons or nerves, Dhandapani says. Additionally the hematoma can damage the brain by literally putting pressure on it, even shoving it aside if the hematoma gets big enough.

Chronic hypertension and plaque buildup inside blood vessels are major risk factors for hemorrhagic stroke. “These are patients who typically have chronic hypertension, so basically their blood vessels are under too much pressure chronically and that is what causes the initial rupture so you get bleeding inside the brain,” Dhandapani says.

Current therapies, which include surgery to remove the blood pool and studies to see if inserting clot-dissolving tPA, which is used successfully for ischemic strokes, into the blood pool can help eliminate the hematoma, are not super effective and surgery itself has associated risks, Dhandapani says. “I think the take home is we don’t have the answer yet for patients with intracerebral hemorrhage,” he says, but RIC may be part of it.

###

Media Contact
Toni Baker
tbaker@augusta.edu

Source: https://bioengineer.org/repetitive-compression-of-limbs-appears-to-aid-recovery-from-deadly-brain-bleeds/

Bioengineer

USC Stem Cell study identifies molecular ‘switch’ that turns precursors into kidney cells

Avatar

Published

on

Kidney development is a balancing act between the self-renewal of stem and progenitor cells to maintain and expand their numbers, and the differentiation of these cells into more specialized cell types. In a new study in the journal eLife from Andy McMahon’s laboratory in the Department of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC, former graduate student Alex Quiyu Guo and a team of scientists demonstrate the importance of a molecule called β-catenin in striking this balance.

β-catenin is a key driver at the end of a complex signaling cascade known as the Wnt pathway. Wnt signaling plays critical roles in the embryonic development of multiple organs including the kidneys. By partnering with other Wnt pathway molecules, β-catenin controls the activity of hundreds to thousands of genes within the cell.

The new study builds on the McMahon Lab’s previous discovery that Wnt/β-catenin can initiate progenitor cells to execute a lengthy and highly orchestrated program of forming structures in the kidney called nephrons. A healthy human kidney contains a million nephrons that balance body fluids and remove soluble waste products. Too few nephrons results in kidney disease.

Previous studies from the UT Southwestern Medical Center laboratory of Thomas Carroll, a former postdoctoral trainee in the McMahon Lab, suggested that Wnt/β-catenin signaling plays opposing roles in ensuring the proper number of nephrons: promoting progenitor maintenance and self-renewal, and stimulating progenitor cell differentiation.

“It sounded like Wnt/β-catenin is doing two things–both maintenance and differentiation–that seem to be opposite operations,” said Guo. “Therefore, the hypothesis was that different levels of Wnt/β-catenin can dictate different fates of the nephron progenitors: when it’s low, it works on maintenance; when it’s high, it directs differentiation.”

In 2015, it became more possible to test this hypothesis when Leif Oxburgh, a scientist at the Rogosin Institute in New York and a co-author of the eLife study, developed a system for growing large numbers of nephron progenitor cells, or NPCs, in a Petri dish.

Relying on this game-changing new system, Guo and his collaborators grew NPCs, added different levels of a chemical that activates β-catenin, and saw their hypothesis play out in the Petri dishes.

They observed that high levels of β-catenin triggered a “switch” in part of the Wnt pathway that relies on another family of transcription factors known as TCF/LEF. There are two types of TCF/LEF transcription factors: one type inhibits genes related to differentiation, and the other activates these genes. In response to high levels of β-catenin, the “activating” members of TCF/LEF switched places with the “inhibiting” members, effectively taking charge. This “switch” triggered NPCs to differentiate into more specialized types of kidney cells.

When they looked at low levels of β-catenin, they saw NPCs self-renewing and maintaining their populations, as expected. However, they were surprised to learn that β-catenin was not engaged with any of the known genes related to self-renewal and maintenance.

“β-catenin does something,” said Guo. “That is for sure. But how it does it is kind of mysterious right now.”

After publishing these results in eLife, Guo earned his PhD from USC, and began his postdoctoral training at UCLA. Helena Bugacov, a current PhD student in the McMahon Lab and a co-author of the eLife study, is now taking the lead in continuing the project–which has implications far beyond the kidney field, due to the broad role of Wnt throughout the body.

“Understanding how Wnt regulates these two very distinct cell outcomes of self-renewal and differentiation, which is very important for kidney development, is also important for understanding the development of other organs and adult stem cells, as Wnt signaling plays important roles in almost all developmental systems,” said Bugacov. “There is also a lot of attention from cancer researchers, as this process can go awry in cancer. Many therapeutics are trying to target this process.”

She added, “The more we know about things, the better we can inform work on developing human kidney organoid cultures, which can be more readily used to understand problems in human health, regeneration and development.”

###

Additional co-authors of the eLife study include: Albert Kim, Andrew Ransick, Xi Chen, and Nils Lindstrom from USC; Aaron Brown from the Maine Medical Center Research Institute; and Bin Li and Bing Ren from the University of California, San Diego. The research was supported by federal funding from the National Institute of Diabetes and Digestive and Kidney Diseases (grant number R01 DK054364).

https://stemcell.keck.usc.edu/usc-stem-cell-study-identifies-molecular-switch-that-turns-precursors-into-kidney-cells/

Coinsmart. Beste Bitcoin-Börse in Europa
Source: https://bioengineer.org/usc-stem-cell-study-identifies-molecular-switch-that-turns-precursors-into-kidney-cells/

Continue Reading

Bioengineer

Evidence of Antarctic glacier’s tipping point confirmed for first time

Avatar

Published

on

Researchers have confirmed for the first time that Pine Island Glacier in West Antarctica could cross tipping points, leading to a rapid and irreversible retreat which would have significant consequences for global sea level

Researchers have confirmed for the first time that Pine Island Glacier in West Antarctica could cross tipping points, leading to a rapid and irreversible retreat which would have significant consequences for global sea level.

Pine Island Glacier is a region of fast-flowing ice draining an area of West Antarctica approximately two thirds the size of the UK. The glacier is a particular cause for concern as it is losing more ice than any other glacier in Antarctica.

Currently, Pine Island Glacier together with its neighbouring Thwaites glacier are responsible for about 10% of the ongoing increase in global sea level.

Scientists have argued for some time that this region of Antarctica could reach a tipping point and undergo an irreversible retreat from which it could not recover. Such a retreat, once started, could lead to the collapse of the entire West Antarctic Ice Sheet, which contains enough ice to raise global sea level by over three metres.

While the general possibility of such a tipping point within ice sheets has been raised before, showing that Pine Island Glacier has the potential to enter unstable retreat is a very different question.

Now, researchers from Northumbria University have shown, for the first time, that this is indeed the case.

Their findings are published in leading journal, The Cryosphere.

Using a state-of-the-art ice flow model developed by Northumbria’s glaciology research group, the team have developed methods that allow tipping points within ice sheets to be identified.

For Pine Island Glacier, their study shows that the glacier has at least three distinct tipping points. The third and final event, triggered by ocean temperatures increasing by 1.2C, leads to an irreversible retreat of the entire glacier.

The researchers say that long-term warming and shoaling trends in Circumpolar Deep Water, in combination with changing wind patterns in the Amundsen Sea, could expose Pine Island Glacier’s ice shelf to warmer waters for longer periods of time, making temperature changes of this magnitude increasingly likely.

The lead author of the study, Dr Sebastian Rosier, is a Vice-Chancellor’s Research Fellow in Northumbria’s Department of Geography and Environmental Sciences. He specialises in the modelling processes controlling ice flow in Antarctica with the goal of understanding how the continent will contribute to future sea level rise.

Dr Rosier is a member of the University’s glaciology research group, led by Professor Hilmar Gudmundsson, which is currently working on a major £4million study to investigate if climate change will drive the Antarctic Ice Sheet towards a tipping point.

Dr Rosier explained: “The potential for this region to cross a tipping point has been raised in the past, but our study is the first to confirm that Pine Island Glacier does indeed cross these critical thresholds.

“Many different computer simulations around the world are attempting to quantify how a changing climate could affect the West Antarctic Ice Sheet but identifying whether a period of retreat in these models is a tipping point is challenging.

“However, it is a crucial question and the methodology we use in this new study makes it much easier to identify potential future tipping points.”

Hilmar Gudmundsson, Professor of Glaciology and Extreme Environments worked with Dr Rosier on the study. He added: “The possibility of Pine Island Glacier entering an unstable retreat has been raised before but this is the first time that this possibility is rigorously established and quantified.

“This is a major forward step in our understanding of the dynamics of this area and I’m thrilled that we have now been able to finally provide firm answers to this important question.

“But the findings of this study also concern me. Should the glacier enter unstable irreversible retreat, the impact on sea level could be measured in metres, and as this study shows, once the retreat starts it might be impossible to halt it.”

###

The paper, The tipping points and early warning indicators for Pine island Glacier, West Antarctica, is now available to view in The Cryosphere.

Northumbria is fast becoming the UK’s leading university for research into Antarctic and extreme environments.

As well as the £4m tipping points study, known as TiPPACCs, Northumbria is also the only UK university to play a part in two projects in the £20m International Thwaites Glacier Collaboration – the largest joint project undertaken by the UK and USA in Antarctica for more than 70 years – where Northumbria is leading the PROPHET and GHC projects. This particular study was funded through both TiPPACCs and PROPHET.

Coinsmart. Beste Bitcoin-Börse in Europa
Source: https://bioengineer.org/evidence-of-antarctic-glaciers-tipping-point-confirmed-for-first-time/

Continue Reading

Bioengineer

Diversity can prevent failures in large power grids

Avatar

Published

on

Integrated power grids offer benefits, but also pose challenges best addressed by leveraging differences

The recent power outages in Texas brought attention to its power grid being separated from the rest of the country. While it is not immediately clear whether integration with other parts of the national grid would have completely eliminated the need for rolling outages, the state’s inability to import significant amounts of electricity was decisive in the blackout.

A larger power grid has perks, but also has perils that researchers at Northwestern University are hoping to address to expedite integration and improvements to the system.

An obvious challenge in larger grids is that failures can propagate further — in the case of Texas, across state lines. Another is that all power generators need to be kept synchronized to a common frequency in order to transmit energy. The U.S. is served by three “separate” grids: The Eastern interconnection, the Western interconnection and the Texas interconnection, interlinked only by direct-current power lines. Any persistent deviation in frequencies within a region can lead to an outage.

As a result, researchers are searching for ways to stabilize the grid by looking for methods to mitigate deviations in the power generators’ frequencies.

The new Northwestern research shows that counter to assumptions held by some, there are stability benefits to heterogeneity in the power grid. Examining several power grids across the U.S. and Europe, a team led by Northwestern physicist Adilson Motter recently reported that generators operating on different frequencies return to their normal state more quickly when they are damped by “breakers” at different rates than generators around them.

The paper was published March 5 in the journal Nature Communications.

Motter is the Charles E. and Emma H. Morrison Professor in the department of physics and astronomy in the Weinberg College of Arts and Sciences. His research focuses on nonlinear phenomena in complex systems and networks.

Motter compares power grids to a choir: “It’s a little bit like a choir without a conductor. The generators have to listen to others and speak in sync. They react and respond to each other’s frequencies.”

Listen to an out-of-whack frequency, and the result can be a failure. Given the interconnected makeup of the system, a failure can propagate across the network. Historically, these malfunctions have been prevented by using active controllers. However, failures are often caused precisely by control and equipment errors. This points to a need to build additional stability within the design of the system. To achieve that, the team looked into leveraging the natural heterogeneities of the grid.

When the frequencies of the power generators are moved away from the synchronous state, they can swing around for a long time and even become more erratic. To mitigate these fluctuations, they came up with something akin to a door mechanism used to close a door the fastest, but without slamming.

“Mathematically, the problem of damping frequency deviations in a power generator is analogous to the problem of optimally damping a door to get it to close the fastest, which has a known solution in the case of a single door,” Motter said. “But it’s not a single door in this analogy. It’s a network of many doors that are coupled with each other, if you can imagine the doors as power generators.”

When creating an “optimal damping” effect, they discovered that rather than making each damper identical, damping the power generators in a way that is suitably different from each other can further optimize their ability to synchronize to the same frequency as quickly as possible. That is, suitably heterogenous damping across the network can lead to improved stability in the power grids studied by the team.

This discovery could have implications for future grid design as developers work to optimize technology and in considerations to further integrate now separated networks.

###

The paper is titled “Asymmetry underlies stability in power grids.” Additional co-authors include former postdoctoral researcher Ferenc Molnar and research professor Takashi Nishikawa.

The study was supported by Northwestern University’s Finite Earth Initiative (supported by Leslie and Mac McQuown) and ARPA-E Award No. DE-AR0000702 and also benefited from logistical support from the Northwestern Institute for Sustainability and Energy.

https://news.northwestern.edu/stories/2021/04/diversity-can-prevent-failures-in-large-power-grids/

Coinsmart. Beste Bitcoin-Börse in Europa
Source: https://bioengineer.org/diversity-can-prevent-failures-in-large-power-grids/

Continue Reading

Bioengineer

How Fortnite and Zelda can up your surgical game (no joke!)

Avatar

Published

on

Scalpel? Check. Gaming console? Check. Study finds video games can be a new tool on surgical tray for medical students

Video games offer students obvious respite from the stresses of studies and, now, a study from a University of Ottawa medical student has found they could benefit surgical skills training.

Arnav Gupta carries a heavy course load as a third-year student in the Faculty of Medicine, so winding down with a game of Legend of Zelda always provides relief from the rigorous of study. But Zelda may be helping improve his surgical education, too, as Gupta and a team of researchers from the University of Toronto found in a paper they recently published in the medical journal Surgery.

“Given the limited availability of simulators and the high accessibility of video games, medical students interested in surgical specialties should know that video games may be a valuable adjunct training for enhancing their medical education, especially in surgical specialties where it can be critical,” says Gupta, whose findings were deciphered from a systematic review of 16 studies involving 575 participants.

“Particularly, in robotic surgery, being a video gamer was associated with improvements in time to completion, economy of motion, and overall performance. In laparoscopic surgery, video games-based training was associated with improvement in duration on certain tasks, economy of motion, accuracy, and overall performance,” explains Gupta, who has been a gamer since age 8.

This study builds on past reviews and is the first to focus on a specific medical student population where this style of training could be feasibly implemented. Their timely study found some of the most beneficial games for students of robotic surgery and laparoscopy were: Super Monkey Ball, Half Life, Rocket League and Underground. Underground is purposely designed to assist medical students with their robotic surgery training via a video game console.

“While video games can never replace the value of first-hand experience, they do have merit as an adjunctive tool, especially when attempting to replicate important movements to surgery. For example, first-person shooting games require you to translate three dimensional motions onto a two-dimensional screen, which is like the concept of laparoscopic surgery,” says Gupta, whose studies are focused on surgery in ophthalmology, which makes games like Resident Evil 4 or Trauma Center: New Blood fitted for his own ambitions.

“I’m not joking when I say that games such as Fortnite have the potential to enhance those necessary movements, providing stronger motivational components and in a low stakes environment.”

Reports suggest 55 percent of university students are gamers and enjoy proficiency with video consoles. Yet, many medical students don’t admit to owning and using a gaming console.

“I think there definitely is some ambivalence towards video games in medicine,” says Gupta, who is also a fan of Witcher 3. “Given how accessible games have become and how video game technology is advancing, video games definitely are an easy go-to for the students who do love them in some capacity. The hope is that maybe this study can inspire someone to take advantage of video games’ unique capabilities, reduce the general ambivalence towards it, and develop some fun ways to let students engage with surgical education.”

###

https://media.uottawa.ca/news/how-fortnite-and-zelda-can-your-surgical-game-no-joke

Coinsmart. Beste Bitcoin-Börse in Europa
Source: https://bioengineer.org/how-fortnite-and-zelda-can-up-your-surgical-game-no-joke/

Continue Reading
Esports2 days ago

Free Fire World Series APK Download for Android

Esports5 days ago

DreamHack Online Open Ft. Fortnite April Edition – How To Register, Format, Dates, Prize Pool & More

Esports5 days ago

Hikaru Nakamura drops chessbae, apologizes for YouTube strike

Esports2 days ago

Dota 2: Top Mid Heroes of Patch 7.29

Esports11 hours ago

Overwatch League 2021 Day 1 Recap

Esports4 days ago

Ludwig Closes Out Month-Long Streaming Marathon in First Place – Weekly Twitch Top 10s, April 5-11

Esports3 days ago

Position 5 Faceless Void is making waves in North American Dota 2 pubs after patch 7.29

Esports5 days ago

Apex Legends update 1.65 brings five new LTMs for War Games

Blockchain5 days ago

Welche Probleme bringen US-Bitcoin ETFs mit sich?

Esports4 days ago

Fortnite: Patch Notes v16.20 – Off-Road Vehicle Mods, 50-Player Creative Lobbies, Bug Fixes & More

Blockchain5 days ago

Which crypto exchange platform is faster, coin transfer or Godex?

Esports5 days ago

Complete guide to romance and marriage in Stardew Valley

Esports4 days ago

Wild Rift patch 2.2a brings tons of champion changes and the addition of Rammus later this month

Esports5 days ago

TenZ on loan to Sentinels through Valorant Challengers Finals

Blockchain4 days ago

Bitcoin Preis steigt auf über 60.000 USD, neues ATH wahrscheinlich

Esports4 days ago

Fortnite Leak Teases Aloy Skin From Horizon Zero Dawn

Esports3 days ago

Capcom Reveals Ransomware Hack Came from Old VPN

Esports5 days ago

flusha announces new CSGO roster featuring suNny and sergej

Esports5 days ago

LoL: MAD Lions Are The New Kings Of Europe, Is The Reign Of G2 Esports And Fnatic Finally Over?

Esports4 days ago

Epic Games Store lost $181 million & $273 million in 2019 and 2020

Trending