Category Archives: Virginia Stem Cells

The immune system usually stays dormant in the lungs in times of health. Overactive immune system can cause issues like asthma and allergies, making it hard to breathe.

Long COVID-19 and other chronic respiratory conditions after viral infections may stem from an overactive immune response in the lungs.

Shortly after the beginning of the COVID-19 pandemic, anecdotal reports emerged of previously healthy individuals that were experiencing lingering symptoms and were not fully recovering from an infection with SARS-CoV-2. These patients started to refer to themselves as Long Haulers, and they coined the term Long COVID.

Viruses that cause respiratory diseases such as the flu and COVID-19 can lead to mild to severe symptoms within the first few weeks of infection. Usually, these symptoms resolve on their own within a few more weeks. Sometimes, if the infection is severe, treatments are needed to aid recovery. However, some people go on to experience persistent symptoms that last several months to years. It is still unclear why and how respiratory diseases can develop into chronic conditions like long COVID-19.

I am a doctoral student working in the Sun Lab at the University of Virginia. We study how the immune system sometimes goes awry after fighting off viral infections. We also develop ways to target the immune system to prevent further complications without weakening its ability to protect against future infections. Our recently published review of the research in this area found that it is becoming clearer that long COVID-19 and similar conditions might not be caused by an active viral infection. Instead, they are caused by an overactive immune system.

Long COVID-19 patients can experience persistent respiratory, cognitive, and neurological symptoms.

For your lungs to be able to function optimally, it is essential that your immune system remain dormant when there isnt an active infection.

People call post-COVID conditions by many names, including: long COVID, chronic COVID, post-acute COVID-19, long-term effects of COVID, post-acute sequelae of SARS CoV-2 infection (PASC), and long-haul COVID.

Your respiratory tract is in constant contact with your external environment, sampling around 5 to 8 liters (1.3 to 2 gallons) of air and the toxins and microorganisms in it every minute. Despite continuous exposure to potential pathogens and harmful substances, your body has evolved to keep the immune system dormant in the lungs. In fact, allergies and conditions such as asthma are byproducts of an overactive immune system. These excessive immune responses can cause your airways to constrict and make it difficult to breathe. Some severe cases may require treatment to suppress the immune system.

During an active infection, however, the immune system is absolutely essential. When viruses infect your respiratory tract, immune cells are recruited to your lungs to fight off the infection. Although these cells are crucial to eliminating the virus from your body, their activity often results in collateral damage to your lung tissue. After the virus is removed, your body dampens your immune system to give your lungs a chance to recover.

An overactive immune system, as in the case of asthma, can damage the lungs.

Over the past decade, scientists have identified a variety of specialized stem cells in the lungs that can help regenerate damaged tissue. These stem cells can turn into almost all the different types of cells in the lungs depending on the signals they receive from their surrounding environment. Recent studies have highlighted the prominent role the immune system plays in providing signals that facilitate lung recovery. But these signals can produce more than one effect. They can not only activate stem cells, but also perpetuate damaging inflammatory processes in the lung. Therefore, your body tightly regulates when, where and how strongly these signals are made in order to prevent further damage.

While the reasons are still unclear, some people are unable to turn off their immune system after infection and continue to produce tissue-damaging molecules long after the virus has been flushed out. This not only further damages the lungs, but also interferes with regeneration via the lungs resident stem cells. This phenomenon can result in chronic disease, as seen in several respiratory viral infections including COVID-19, Middle East Respiratory Syndrome (MERS), respiratory syncytial virus (RSV), and the common cold.

In our review, my colleagues and I found that many different types of immune cells are involved in the development of chronic disease after respiratory viral infections, including long COVID-19.

Researchers so far have identified one particular type of immune cell, killer T cells, as potential contributors to chronic disease. Also known as cytotoxic or CD8+ T cells, they specialize in killing infected cells either by interacting directly with them or by producing damaging molecules called cytokines.

Killer T cells are essential to curbing the virus from spreading in the body during an active infection. But their persistence in the lungs after the infection has resolved is linked to extended reduced respiratory function. Moreover, animal studies have shown that removing killer T cells from the lungs after infection may improve lung function and tissue repair.

A legion of immune cells work together to remove invading pathogens.

Another type of immune cell called monocytes are also involved in fighting respiratory infections, serving among the first responders by producing virus- and tissue-damaging cytokines. Research has found that these cells also continue to accumulate in the lungs of long COVID-19 patients and promote a pro-inflammatory environment that can cause further damage.

Understanding the immunological mechanisms underlying long COVID-19 is the first step to addressing a quickly worsening public health problem. Identifying the subtle differences in how the same immune cells that protect you during an active infection can later become harmful could lead to earlier diagnosis of long COVID-19. Moreover, based on our findings, my team and I believe treatments that target the immune system could be an effective approach to manage long COVID-19 symptoms. We believe that this strategy may turn out to be useful not only for COVID-19, but also for other respiratory viral infections that lead to chronic disease as well.

Written by Harish Narasimhan, PhD Candidate in Immunology, University of Virginia.

This article was first published in The Conversation.

Go here to read the rest:
Long COVID-19 May Stem From an Overactive Immune Response in the Lungs - SciTechDaily

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

(THE CONVERSATION) Viruses that cause respiratory diseases like the flu and COVID-19 can lead to mild to severe symptoms within the first few weeks of infection. These symptoms typically resolve within a few more weeks, sometimes with the help of treatment if severe. However, some people go on to experience persistent symptoms that last several months to years. Why and how respiratory diseases can develop into chronic conditions like long COVID-19 are still unclear.

I am a doctoral student working in the Sun Lab at the University of Virginia. We study how the immune system sometimes goes awry after fighting off viral infections. We also develop ways to target the immune system to prevent further complications without weakening its ability to protect against future infections. Our recently published review of the research in this area found that it is becoming clearer that it might not be an active viral infection causing long COVID-19 and similar conditions, but an overactive immune system.

The lungs in health and disease

Keeping your immune system dormant when there isnt an active infection is essential for your lungs to be able to function optimally.

Your respiratory tract is in constant contact with your external environment, sampling around 5 to 8 liters (1.3 to 2 gallons) of air and the toxins and microorganisms in it every minute. Despite continuous exposure to potential pathogens and harmful substances, your body has evolved to keep the immune system dormant in the lungs. In fact, allergies and conditions such as asthma are byproducts of an overactive immune system. These excessive immune responses can cause your airways to constrict and make it difficult to breathe. Some severe cases may require treatment to suppress the immune system.

During an active infection, however, the immune system is absolutely essential. When viruses infect your respiratory tract, immune cells are recruited to your lungs to fight off the infection. Although these cells are crucial to eliminate the virus from your body, their activity often results in collateral damage to your lung tissue. After the virus is removed, your body dampens your immune system to give your lungs a chance to recover.

Over the past decade, researchers have identified a variety of specialized stem cells in the lungs that can help regenerate damaged tissue. These stem cells can turn into almost all the different types of cells in the lungs depending on the signals they receive from their surrounding environment. Recentstudieshave highlighted the prominent role the immune system plays in providing signals that facilitate lung recovery. But these signals can produce more than one effect. They can not only activate stem cells, but also perpetuate damaging inflammatory processes in the lung. Therefore, your body tightly regulates when, where and how strongly these signals are made in order to prevent further damage.

While the reasons are still unclear, some people are unable to turn off their immune system after infection and continue to produce tissue-damaging moleculeslong after the virus has been flushed out. This not only further damages the lungs, but also interferes with regeneration via the lungs resident stem cells. This phenomenon can result in chronic disease, as seen in several respiratory viral infections including COVID-19, Middle East Respiratory Syndrome (MERS), respiratory syncytial virus (RSV) and the common cold.

The immune systems role in chronic disease

In our review, my colleagues and I found that many different types of immune cells are involved in the development of chronic disease after respiratory viral infections, including long COVID-19.

Scientists so far have identified one particular type of immune cells, killer T cells, as potential contributors to chronic disease. Also known as cytotoxic or CD8+ T cells, they specialize in killing infected cells either by interacting directly with them or by producing damaging molecules called cytokines.

Killer T cells are essential to curbing the virus from spreading in the body during an active infection. But their persistence in the lungs after the infection has resolved is linked to extended reduced respiratory function. Moreover, animal studies have shown that removing killer T cells from the lungs after infection may improve lung function and tissue repair.

Another type of immune cells called monocytes are also involved in fighting respiratory infections, serving among the first responders by producing virus- and tissue-damaging cytokines. Research has found that these cells also continue to accumulate in the lungs of long COVID-19 patients and promote a pro-inflammatory environment that can cause further damage.

Understanding the immunological mechanisms underlying long COVID-19 is the first step to addressing a quickly worsening public health problem. Identifying the subtle differences in how the same immune cells that protect you during an active infection can later become harmful could lead to earlier diagnosis of long COVID-19. Moreover, based on our findings, my team and I believe treatments that target the immune system could be an effective approach to manage long COVID-19 symptoms. We believe that this strategy may turn out to be useful not only for COVID-19, but also for other respiratory viral infections that lead to chronic disease as well.

This article is republished from The Conversation under a Creative Commons license. Read the original article here: https://theconversation.com/long-covid-19-and-other-chronic-respiratory-conditions-after-viral-infections-may-stem-from-an-overactive-immune-response-in-the-lungs-186970.

Visit link:
Long COVID-19 and other chronic respiratory conditions after viral infections may stem from an overactive immune response in the lungs - Huron Daily...

Visit the News Hub

Oncologist honored for outstanding work on leukemia

DiPersio

John F. DiPersio, MD, PhD, the Virginia E. and Sam J. Golman Endowed Professor of Oncology and director of the Division of Oncology at Washington University School of Medicine in St. Louis, has been named by OncLive as part of the Giants of Cancer Care inductee class of 2022.

The Giants of Cancer Care honor recognizes oncologists who have made groundbreaking contributions to research and clinical practice. OncLive is a news and multimedia resource for oncology professionals. DiPersio, one of 14 honored this year, was recognized for his contributions to the understanding and treatment of leukemia.

DiPersio who also serves as deputy director of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine is a leader in developing novel therapies for leukemia and in understanding how such therapies work. Among other accomplishments, he has developed strategies to optimize CAR-T cell therapies, a type of cell-based immunotherapy that attacks cancer cells. His work also includes improving management of graft-versus-host disease, a sometimes life-threatening condition that some patients develop after a stem cell transplant.

See original here:
DiPersio receives awards recognizing contributions to cancer care, research Washington University School of Medicine in St. Louis - Washington...

People protest near City Hall in downtown Los Angeles after the U.S. Supreme Court released its decisions regarding Roe v. Wade. With this recent slate of decisions regarding abortion, gun rights, and the environment, columnist Joe Mathews argues that America may be pushing California to leave the nation. Courtesy of AP Images.

by Joe Mathews|July5,2022

To encourage us to think about the unthinkable, the Bulletin of the Atomic Scientists sets a Doomsday Clock, showing how close humanity is (in metaphorical minutes and seconds) to the midnight of the apocalypse (nuclear or otherwise) and human extinction.

California may now need its own Independence Clock, showing how close we are to that seemingly unthinkable moment when our state departs the U.S., to become an independent nation.

In recent weeks, that prospect drew unmistakably closer, courtesy of the U.S. Supreme Court.

First, justices overturned more than a century of legal precedent that had allowed communities in California to limit public gun possessionendangering laws that have spared us from some of the American epidemic of gun deaths by murder, suicide, and accident.

Then, the court reversed Roe v. Wade and eliminated the federal constitutional right to abortiona right enshrined in our state constitution and supported by majorities of Californians of every political party, region, and demographic group.

These decisions were like earthquakesunsettling but unsurprising, given the justices frequent expressions of contempt for California in oral arguments (a bias I wrote about last year). They were enacted by a far-right court majority that exists because Americas anti-democratic constitution gives less representation and less voting power to Californians, both in choosing a president (who nominates justices) and in electing a Senate (which confirms them).

The two decisions follow a fusillade of recent federal failings that have damaged California and harmed our people. These include a pandemic response that cost nearly 100,000 Californian lives; a generation-long war on terror that killed more soldiers from California than from any other state; attacks on our efforts to end the drug war and police abuses; attempts to cancel our environmental laws; denial and delay of disaster aid; accusations that our elections are fraudulent; and the violation of the rights of our immigrants and their families.

Departing the union seems beyond the pale. But so is the behavior of the American government. Thats why, as fanciful as a break-up of the country might still sound, the Independence Clock is ticking closer to midnight.

To cope, California has had to behave more like a separate nation than a state. We have adopted our own immigration policy. We have signed our own environmental treaties with other countries (agreements that are even more important now that the Supreme Court has limited the federal governments ability to regulate climate change). We have funded our own research on subjects from guns to stem cells (in response to federal restrictions on such research). And we have successfully pressured car makers and other corporations to privilege our state regulations over national ones, just to name a few.

But creating a quasi-nation creates costs that are hard on Californians. We werent designed to operate as an island. How much more can a state handle, governmentally, economically, emotionally?

The Supreme Court made clear last week that we can expect no respite in the future.

I say this not just because the court, for the first time, cancelled a constitutional right in the abortion case, or because Clarence Thomas, in his concurrence, declared that the courts should cancel the rights to contraception and same-sex marriage. I say this because the courts method of decision-making does not account for Californians lives or preferences.

Both the guns and abortion decisions rely on peculiar readings of historyfocused on American and English practices of the 18th, 17th, and earlier centuries, generations before womens suffrage, before the end of slavery, before California was even a state. The decisions employ a mode of historical analogy that lacks the rigor of palm reading, much less serious legal analysis.

The troubles will persist beyond this court, which, with the retirement of Stephen Breyer, no longer has a single Californian among its justices. Given our disenfranchisement, what is to stop a future Congress and president from cancelling our abortion laws, our protections for women or gay people or minorities or immigrants, our climate and environmental laws, or even our commitment to making it easier for our people to vote?

As an optimist, Ive previously argued that democratic reforms in California and elsewhere could solve this American crisis. With more and better participatory toolsfrom citizens assemblies to proportional representation to national referendathe U.S. could re-found itself as a modern democracy. But the open hostility to democracy of this court, and among much of the American political elite, suggests that any such reforms do not stand a chance.

Departing the union seems beyond the pale. But so is the behavior of the American government. Thats why, as fanciful as a break-up of the country might still sound, the Independence Clock is ticking closer to midnight.

Polling from last year showed growing support, among Americans of all political persuasions, for removing their own state from the U.S. A University of Virginia poll found 41 percent support among Biden voters and 52 percent support among Trump voters for blue or red states seceding to form their own separate nations. A Bright Line Watch poll found that 47 percent of Democrats in West Coast states favor forming their own nation.

Is it time for California to go? Probably not. But its not too early to pack a bag and make a departure plan. We badly need an open and ongoing statewide conversation, including major media and our elected leaders, about independence.

The day after Roe v. Wade fell, I found myself coaching in a youth sports tournament, which starts every game with the Pledge of Allegiance. I stood and put my hand over my heart, but found that I could no longer bring myself to recite the words.

More here:
With Supreme Court Failing California, Is It Time to Go on Our Own? - zocalopublicsquare.org

PARP inhibitors, including olaparib (Lynparza) and talazoparib (Talzenna), have changed the treatment paradigm for patients with BRCA-mutated breast cancer. However, further work must be done to see whether other subsets of patients can benefit from the use of PARP inhibitors, according to Virginia G. Kaklamani, MD.

[We have] emerging data with [PARP inhibitors in] patients that have BRCA-like tumors. This is where a lot of work is being done, to see whether PARP inhibitors, either by themselves or in combination with immunotherapy or chemotherapy, might help improve outcomes in our patients, Kaklamani said in an interview with OncLive following an Institutional Perspectives in Cancer (IPC) webinar on breast cancer.

In the interview, Kaklamani, the chair of the IPC program, discussed the main takeaways from the meeting, which included the emerging role of PARP inhibitors, practice-changing updates in HER2-positive breast cancer, the utilization of CDK4/6 inhibitors in hormone receptor (HR)positive, HER2-negative breast cancer, and the various therapeutic classes and their effects on care in triple-negative breast cancer (TNBC). Kaklamani is a professor of medicine in the Division of Hematology/Oncology at UT Health San Antonio, and the leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center.

Kaklamani: For early-stage HER2-positive breast cancer, 1 of the biggest updates is the data from the phase 3 KATHERINE trial [NCT01772472], which showed the patients who had [minimal] residual disease [MRD] after neoadjuvant chemotherapy benefited from the addition of ado-trastuzumab emtansine [T-DM1; Kadcyla] to their treatment instead of continuing trastuzumab [Herceptin]-based therapy.

Another pivotal trial was [the phase 3 APHINITY trial (NCT01358877), which examined] the addition of pertuzumab [(Perjeta) to trastuzumab and chemotherapy] in the adjuvant setting. [APHINITY] showed that for certain patient populations, adding pertuzumab to trastuzumab [and chemotherapy] improved their outcomes.

Based on these trials, the early-stage HER2-positive setting has changed such that most patients diagnosed with this type of disease are being cured.

In the past 2 years, [there have been] several new drug approvals because of data from several pivotal clinical trials. The phase 2 HER2CLIMB trial [NCT02614794] looked at the addition of tucatinib [Tukysa] to [trastuzumab and capecitabine] and showed that tucatinib improves outcomes in patients with metastatic HER2-positive breast cancer, including patients with active brain metastases.

Another pivotal trial was the phase 3 DESTINY-Breast03 trial [NCT03529110], which is looking at the [use] of fam-trastuzumab deruxtecan-nxki [Enhertu], an antibody-drug conjugate [ADC], in the second-line setting. Results showed that trastuzumab deruxtecan improved outcomes compared with T-DM1.

We have some older clinical trials, such as the phase 3 CLEOPATRA trial [NCT00567190], which gave us a first-line standard-of-care therapy with a taxane, trastuzumab, and pertuzumab. Other drugs that have been shown to improve outcomes, such as margetuximab-cmkb [Margenza], are also approved and have changed how we treat our patients with HER2-positive breast cancer. [Margetuximab was approved based on] the data from the phase 3 SOPHIA trial [NCT02492711].

In the adjuvant or neoadjuvant setting, we have to re-stratify patients. We have to decide what the risk of recurrence is, and, right now, our ways of stratifying those risks have to do with clinical pathologic factors. How big is a tumor? Is there lymph node involvement? [Subsequent treatment decisions] also have to do with how well neoadjuvant chemotherapy has worked. If the chemotherapy has worked well, producing a pathologic complete response, then adjuvant therapy is more streamlined.

We still have a long way to go. There are other, more molecularly targeted ways of stratifying patients. Were still not there yet. We still have to validate several of these assays to give us [a better] understanding of [which] patients have a higher risk of recurrence.

[For] some of the patients that have a higher risk of recurrence, we may need to add extended adjuvant therapy with neratinib [Nerlynx], as seen in the phase 3 ExteNET trial [NCT00878709]. For some patients, we may be able to give them single-agent antibody therapy with trastuzumab and a taxane. [It is important to treat] patients based on their risk and [to treat] them the right way. [We do not want to give] patients too much or too little treatment, but our goal is to cure all these patients.

In the metastatic setting, 1 of the factors that help us determine how to treat our patients is whether they have developed brain metastases. Tucatinib and other TKIs have shown good data in treating patients with brain metastases. Typically, we tend to favor tucatinib in that setting. If patients have not developed brain metastases, then an ADC, such as trastuzumab deruxtecan or T-DM1, might be a good option for these patients.

The important thing with metastatic HER2-positive breast cancer is looking at it as a chronic disease. These patients can survive for many years, and we must pace ourselves with treatment. We should not be extremely aggressive up front unless the patient seems to have very aggressive disease. [We need to realize] that these patients are going to be on treatment for many years to come, and, therefore, symptoms are extremely important to keep an eye out for because if we do give [patients] a lot of symptoms with their first- or second-line therapy, they may not have a good [enough] performance status to receive third-, fourth-, or fifth-line therapy.

In [2021], we [received] pivotal data from the phase 3 OlympiA trial [NCT02032823], which is looking at olaparib in the adjuvant setting. That study changed how we treat patients with BRCA1 or BRCA2 mutations [such that we now] give olaparib as long as they have a high enough risk to warrant that strategy.

In the metastatic setting, we have data from the phase 3 OlympiAD trial [(NCT02000622), which examined olaparib vs chemotherapy] and the phase 3 EMBRACA trial [NCT01945775], which looked at talazoparib [vs chemotherapy]. [These trials showed] that [PARP inhibitors] improve outcomes compared with single-agent chemotherapy. However, a small number of patients will be germline BRCA positive. Is there another subset of patients that might benefit from these drugs?

One of the subsets that may benefit from PARP inhibitors is patients with PALB2 mutations. Another subset of patients that seem to benefit from [PARP inhibitors] are those that have somatic mutations in the BRCApathway.

In this field, CDK4/6 inhibitors are the big story and have been the big story since 2015, when [palbociclib (Ibrance)], the first CDK4/6 inhibitor, was approved. Recently, weve had some data in the metastatic setting that showed overall survival [OS] benefit with ribociclib [Kisqali] and some OS benefit with abemaciclib [Verzenio], as well.

In the adjuvant setting, recent data from the phase 3 monarchE trial [(NCT03155997) showed] that abemaciclib can help improve outcomes, and now abemaciclib [is] approved in the adjuvant setting.

There are other pathways, such as the PI3K pathway, where patients who have PIK3CA mutations may benefit from alpelisib [Piqray], given the results from the phase 3 SOLAR-1 trial [NCT02437318].

We have some older drugs such as mTOR inhibitors that we use. New data on oral selective estrogen receptor degraders [SERDs] show that we may be coming up with a different category of drugs altogether to use in that setting. One of the things that were still trying to tackle is endocrine resistance. Importantly, the most recent data with CDK4/6 inhibitors suggest that, especially when we use them in the first-line setting, patients can have an OS of more than 5 years, which is impressive, given the fact that up until a few years ago, OS in metastatic disease was around 2 years.

We have the emergence of immunotherapy, both in the early-stage and in the metastatic setting. The results from the phase 3 KEYNOTE-522 trial [NCT03036488] in the neoadjuvant setting suggest that there is long-term improvement in outcomes with the use of pembrolizumab [Keytruda]. In the metastatic setting, the use of pembrolizumab and atezolizumab [(Tecentriq) demonstrated] that in the subset of patients that have a PD-L1positive tumor, there may be an improvement in OS and progression-free survival with the use of PD-1/PD-L1 inhibitors.

There is the emergence of ADCs, such as sacituzumab govitecan-hziy [Trodelvy], showing improvement in outcomes. More recently, there was a press release [on sacituzumab govitecan in] HER2-low breast cancer. Some of these HER2-low breast cancers can be estrogen receptor [ER] positive, but they can also be triple negative, suggesting that another ADC, trastuzumab deruxtecan, which we use in HER2-positive breast cancer, can also be active in the HER2-low subset. This is exciting because now we have more data in [the HER2-low] subset of breast cancer.

This is extremely difficult, and the same goes with the use abemaciclib, as well as olaparib, in patients with ER-positive breast cancer. Which 1 of the 2 agents do you pick? The answer is we dont know. Many [clinicians] are combining these drugs, especially if we have safety data. Combining pembrolizumab with a PARP inhibitor and then continuing adjuvant pembrolizumab is relatively safe and may potentially be effective, especially in patients who have not achieved a pathologic complete response with neoadjuvant chemotherapy based on the KEYNOTE-522 trial. Adding a PARP inhibitor, olaparib in that case, may be beneficial. We dont have the data with the combination [of pembrolizumab and olaparib], but most of us are doing this because these patients dont have good outcomes.

In the ER-positive subset, we have patients who have high-risk disease but are also BRCA positive where you are struggling to determine whether to give olaparib or abemaciclib to these patients. Ive used the approach of giving olaparib for 1 year, [followed by] abemaciclib for another 2 years, but, again, this is not based on any data. This is just based on extrapolating from different clinical trials.

As in other malignancies, the addition of immunotherapy and more targeted agents has changed the landscape of how we treat breast cancer, improving outcomes and OS in our patients.

There are lot of new drugs approved and a lot of new drugs that come with their own toxicities. It is important for clinicians to understand how and when to use these drugs and when its worth using them, given the potential toxicities. Overall, this is a busy field and busy for good reason because were helping improve outcomes for our patients.

[Our] ongoing research [relates] to drugs looking at attacking breast cancer stem cells. We all know that cancers in general arise from stem cells, and there is a subset of agents, such as mTOR inhibitors, that can destroy stem cells. We have used that approach in patients with ductal carcinoma in situ, with the hope that these would be the type of agents to help prevent breast cancer altogether.

We are also doing work on patients with brain metastases with the use of sacituzumab govitecan in patients with brain metastases, as well as a radioactive particle in patients with leptomeningeal disease, trying to see whether this most aggressive type of brain recurrence can be treated with the use of radioactive isoforms.

More here:
PARP Inhibitors Are Under Study as Treatment Options Beyond BRCA-Mutated Breast Cancer - OncLive

Winning an award is nice, of course, but thats only a small reason to do a science fair project. Theres learning about science, how to conduct an experiment and working with others to achieve a goal. And competing itself is its own reward, say alumni of the International Science and Engineering Fair, or ISEF.

This week, more than 1,700 teens have gathered online and in Atlanta, Ga., for the 2022 Regeneron ISEF. These high-school students have competed in science fairs across the globe for the right to show off their work. Now theyre vying for nearly $8 million in scholarships and other prizes. (This annual competition is held by the Society for Science, which also publishes Science News for Students.)

To get a bit of insight into the ISEF experience, Science News for Students spoke with four recent competitors. Heres what they said about competing in the so-called Olympics of science fairs.

Weekly updates to help you use Science News for Students in the learning environment

Thank you for signing up!

There was a problem signing you up.

Jacob competed in ISEF from 2015 to 2018. For his projects, he revamped a 3-D printer to print with multiple materials and optimized inks to print electronics and solar cells. He now works at the 3-D printing company Inkbit, which is based in Medford, Mass.

How would you describe ISEF?

Id definitely compare it to the Olympics of science fair, Jacob says. But its not just a science fair, he adds. Its an incredible social experience for like-minded high schoolers who are interested in science research. The week of ISEF is full of opportunities to socialize such as a dance party and a massive pin exchange between competitors. You get to meet people from all over, Jacob says. You have a lot of fun just going to different activities and exploring interests and having interesting conversations with other people your age.

What makes a good science fair project?

One of the biggest things is just picking a topic that you find interesting, Jacob says. Some students will try to do something that they think will win. And it makes it harder to put in a lot of work in time, if your hearts not in it. Some of the best projects, he adds, involve combining multiple interests.

Any advice for science fair newbies?

Staying on top of the news, Jacob says. Our middle school teacher showed us Science News and a couple of other websites that he just suggested reading every day, so that it got your brain thinking about: What do we know in science? And what dont we know? And then, finding the middle ground of what we do know and what we dont know to create your own project.

Rimoldi Ibanez competed in ISEF in 2018, 2019 and 2021. Her first projects investigated materials to limit radiation given off by smartphones. She then started studying how corals communicate through sound waves. Rimoldi Ibanez is currently a freshman at Florida Atlantic University in Jupiter.

What challenges did you face in your project?

When she first started studying corals, Rimoldi Ibanez tried growing them at home. Its the hardest thing ever! she says. I dont recommend it. For one thing, the corals were very sensitive. Also, creating a realistic ecosystem required filling the tank with fish, crabs and other creatures. The crabs and the shrimp just went after every single fish, she says. But the bright side of that project was that I was able to see that there were some acoustical sounds being emitted from the corals. The next year, Rimoldi Ibanez studied sound waverelated genes in corals at a research lab.

What was most memorable about ISEF?

Becoming part of this community that is so welcoming and excited to get to know each other. Thats really, really cool, Rimoldi Ibanez says. I love a good dance party, and they do a really good job with the dance parties at ISEF.

How has ISEF impacted your life?

I was very shy, as a middle schooler and in elementary. Because, when I moved here from Argentina, I did not know English, Rimoldi Ibanez says. But presenting at science fairs helped Rimoldi Ibanez gain confidence in talking to strangers. At first, my face would get super red when theyd ask me a question, she says. But later I realized, well, hey. Im the one who did all this work. I know all this information. Wanting to enjoy the social events at ISEF pushed her to be more outgoing, too. If youre shy and standing back, she says, youre not gonna get the same out of those events as someone who might be more confident.

In 2016, Toro Vega competed in ISEF with a project that simulated radioactive decay. In 2017, he returned as part of a team that built a hydroelectric energy generator. Today, hes a product manager at Apple in San Francisco, Calif.

What is it like working on a team, versus doing a solo project?

Working by yourself, you have the whole independence of leading a project, Toro Vega says. In a team, you have the opportunity to skill-share, divide the work. Teamwork is also good prep for working in the real world, he says. As a team, you actually learn how to communicate, manage deadlines, expectations between one another and at the same time, learn from each other. Plus, Toro Vega adds, joining forces with a friend can make doing a project more fun.

How has ISEF impacted your life?

I didnt really know what I wanted to study [in college], Toro Vega says. I knew I wanted to study STEM [science, technology, engineering and math], but going to ISEF and just walking around the computer science projects was like, I want to do this in the future. Having high-school research experience was also a huge bonus for college applications, he says.

Any advice for science fair newbies?

Just go for it, Toro Vega says. It might seem like its a huge road ahead. But the first step, the hardest step, is just starting. If youre unsure what topic to study, pick a few things that interest you and read about them online, he says. See if theres an issue that really calls out to you. And dont be afraid of failure, Toro Vega adds. Science isnt all about solutions that work. There are solutions that dont work, and from that we actually learn.

Wagner competed in ISEF from 2015 to 2017. She studied how to improve sporting helmets using inspiration from a woodpeckers head. Wagner now teaches high school chemistry in Saginaw, Mich.

What challenges did you face in your project?

Every step in science fair will give you a different problem to solve, Wagner says. For instance, I tested my helmets using a testing rig that Virginia Tech designed based off of real player data, and I replicated it in my garage. It was, like, 12 feet tall, built by hand myself. That took about three months, Wagner says. And you dont really get a lot of credit for all the hard work that you put into a project, not even the data you want to talk about.

Any advice for science fair newbies?

Any question that you can come up with about the world, in general, can become a science fair project, Wagner says. Keep asking questions. Be curious. And do it with a friend, if you really are discouraged about doing a project.

How would you describe ISEF?

I know a lot of people call it the Olympics of science fair, but it really is, Wagner says. And if youre a math nerd and you do the probability of making it to the Olympics versus making it to science fair, its actually harder to make it to ISEF.

What was most memorable about ISEF?

When you first arrive to ISEF, you meet students that are just like you, and you realize that youre not alone, Wagner says. You now have friends across the entire globe that are participating in a similar experience. And obviously winnings really nice and amazing and is an indescribable feeling. But the true prize is the experience itself.

Continue reading here:
What it's like to compete in the science fair 'Olympics' - Science News for Students

image:The new multi-organ chip has the size of a glass microscope slide and allows the culture of up to four human engineered tissues, whose location and number can be tailored to the question being asked. These tissues are connected by vascular flow, but the presence of a selectively permeable endothelial barrier maintains their tissue-specific niche. view more

Credit: Kacey Ronaldson-Bouchard/Columbia Engineering

New York, NYApril 27, 2022Engineered tissues have become a critical component for modeling diseases and testing the efficacy and safety of drugs in a human context. A major challenge for researchers has been how to model body functions and systemic diseases with multiple engineered tissues that can physiologically communicate - just like they do in the body. However, it is essential to provide each engineered tissue with its own environment so that the specific tissue phenotypes can be maintained for weeks to months, as required for biological and biomedical studies. Making the challenge even more complex is the necessity of linking the tissue modules together to facilitate their physiological communication, which is required for modeling conditions that involve more than one organ system, without sacrificing the individual engineered tissue environments.

Novel plug-and-play multi-organ chip, customized to the patient

Up to now, no one has been able to meet both conditions. Today, a team of researchers from Columbia Engineering and Columbia University Irving Medical Center reports that they have developed a model of human physiology in the form of a multi-organ chip consisting of engineered human heart, bone, liver, and skin that are linked by vascular flow with circulating immune cells, to allow recapitulation of interdependent organ functions. The researchers have essentially created a plug-and-play multi-organ chip, which is the size of a microscope slide, that can be customized to the patient. Because disease progression and responses to treatment vary greatly from one person to another, such a chip will eventually enable personalized optimization of therapy for each patient. The study is the cover story of the April 2022 issue of Nature Biomedical Engineering.

This is a huge achievement for usweve spent ten years running hundreds of experiments, exploring innumerable great ideas, and building many prototypes, and now at last weve developed this platform that successfully captures the biology of organ interactions in the body, said the project leader Gordana Vunjak-Novakovic, University Professor and the Mikati Foundation Professor of Biomedical Engineering, Medical Sciences, and Dental Medicine.

Inspired by the human body

Taking inspiration from how the human body works, the team has built a human tissue-chip system in which they linked matured heart, liver, bone, and skin tissue modules by recirculating vascular flow, allowing for interdependent organs to communicate just as they do in the human body. The researchers chose these tissues because they have distinctly different embryonic origins, structural and functional properties, and are adversely affected by cancer treatment drugs, presenting a rigorous test of the proposed approach.

Providing communication between tissues while preserving their individual phenotypes has been a major challenge, said Kacey Ronaldson-Bouchard, the studys lead author and an associate research scientist in Vunjak-Novakovics Laboratory for Stem Cells and Tissue Engineering. Because we focus on using patient-derived tissue models we must individually mature each tissue so that it functions in a way that mimics responses you would see in the patient, and we dont want to sacrifice this advanced functionality when connecting multiple tissues. In the body, each organ maintains its own environment, while interacting with other organs by vascular flow carrying circulating cells and bioactive factors. So we chose to connect the tissues by vascular circulation, while preserving each individual tissue niche that is necessary to maintain its biological fidelity, mimicking the way that our organs are connected within the body.

Optimized tissue modules can be maintained for more than a month

The group created tissue modules, each within its optimized environment and separated them from the common vascular flow by a selectively permeable endothelial barrier. The individual tissue environments were able to communicate across the endothelial barriers and via vascular circulation. The researchers also introduced into the vascular circulation the monocytes giving rise to macrophages, because of their important roles in directing tissue responses to injury, disease, and therapeutic outcomes.

All tissues were derived from the same line of human induced pluripotent stem cells (iPSC), obtained from a small sample of blood, in order to demonstrate the ability for individualized, patient-specific studies. And, to prove the model can be used for long-term studies, the team maintained the tissues, which had already been grown and matured for four to six weeks, for an additional four weeks, after they were linked by vascular perfusion.

Using the model to study anticancer drugs

The researchers also wanted to demonstrate how the model could be used for studies of an important systemic condition in a human context and chose to examine the adverse effects of anticancer drugs. They investigated the effects of doxorubicin a broadly used anticancer drug on heart, liver, bone, skin, and vasculature. They showed that the measured effects recapitulated those reported from clinical studies of cancer therapy using the same drug.

The team developed in parallel a novel computational model of the multi-organ chip for mathematical simulations of drugs absorption, distribution, metabolism, and secretion. This model correctly predicted doxorubicins metabolism into doxorubicinol and its diffusion into the chip. The combination of the multi-organ chip with computational methodology in future studies of pharmacokinetics and pharmacodynamics of other drugs provides an improved basis for preclinical to clinical extrapolation, with improvements in the drug development pipeline.

While doing that, we were also able to identify some early molecular markers of cardiotoxicity, the main side-effect that limits the broad use of the drug. Most notably, the multi-organ chip predicted precisely the cardiotoxicity and cardiomyopathy that often require clinicians to decrease therapeutic dosages of doxorubicin or even to stop the therapy," said Vunjak-Novakovic.

Collaborations across the university

The development of the multi-organ chip began from a platform with the heart, liver, and vasculature, nicknamed the HeLiVa platform. As is always the case with Vunjak-Novakovics biomedical research, collaborations were critical for completing the work. These include the collective talent of her laboratory, Andrea Califano and his systems biology team (Columbia University), Christopher S. Chen (Boston University) and Karen K. Hirschi (University of Virginia) with their expertise in vascular biology and engineering, Angela M. Christiano and her skin research team (Columbia University), Rajesh K. Soni of the Proteomics Core at Columbia University, and the computational modeling support of the team at CFD Research Corporation.

A multitude of applications, all in individualized patient-specific contexts

The research team is currently using variations of this chip to study, all in individualized patient-specific contexts: breast cancer metastasis; prostate cancer metastasis; leukemia; effects of radiation on human tissues; the effects of SARS-CoV-2 on heart, lung, and vasculature; the effects of ischemia on the heart and brain; and the safety and effectiveness of drugs. The group is also developing a user-friendly standardized chip for both academic and clinical laboratories, to help utilize its full potential for advancing biological and medical studies.

Vunjak-Novakovic added, After ten years of research on organs-on-chips, we still find it amazing that we can model a patients physiology by connecting millimeter sized tissues the beating heart muscle, the metabolizing liver, and the functioning skin and bone that are grown from the patients cells. We are excited about the potential of this approach. Its uniquely designed for studies of systemic conditions associated with injury or disease, and will enable us to maintain the biological properties of engineered human tissues along with their communication. One patient at a time, from inflammation to cancer!

###

About the Study

Journal: Nature Biomedical Engineering

The study is titled A multi-organ chip with matured tissue niches linked by vascular flow

Authors are: Kacey Ronaldson-Bouchard1, Diogo Teles1,2,3, Keith Yeager1, Daniel Naveed Tavakol 1, Yimu Zhao1, Alan Chramiec1, Somnath Tagore4, Max Summers1, Sophia Stylianos1, Manuel Tamargo1, Busub Marcus Lee1, Susan P. Halligan1, Erbil Hasan Abaci5, Zongyou Guo5, Joanna Jackw5, Alberto Pappalardo5, Jerry Shih6, Rajesh K. Soni7, Shivam Sonar8, Carrie German8, Angela M. Christiano5,9, Andrea Califano4,7,10-13, Karen K. Hirschi14, Christopher S. Chen6, Andrzej Przekwas8 and Gordana Vunjak-Novakovic1,12,15 1 Department of Biomedical Engineering, Columbia University, New York City, NY, USA.2 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.3 ICVS/3Bs, PT Government Associate Laboratory, Braga/Guimares, Braga, Portugal.4 Department of Systems Biology, Columbia University, New York City, NY, USA.5 Department of Dermatology, Columbia University, New York City, NY, USA.6 Department of Biomedical Engineering, Boston University, The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.7 Herbert Irving Comprehensive Cancer Center, Columbia University, New York City, NY, USA.8 CFD Research Corporation, Huntsville, AL, USA.9 Department of Genetics and Development, Columbia University, New York City, NY, USA.10 Department of Biomedical Informatics, Columbia University, New York, New York.11 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York.

12 Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.

13 J.P. Sulzberger Columbia Genome Center, New York, NY, USA.

14 Department of Cell Biology, University of Virginia, Charlottesville, VA, USA.

15 College of Dental Medicine, Columbia University, New York, NY, USA.

The study was supported by the NIH (UG3 EB025765, P41 EB027062, and R01 CA249799 to G.V.-N.; R35 CA197745, S10 OD012351, and S10 OD021764 to An.C.; UL1 TR001873 to the Irving Institute for Clinical and Translational Research; P30 CA013696 to the Confocal and Specialized Microscopy Shared Resource), NSF (Engineering Research Center EEC-1647837 to C.S.C. and G.V.-N., Graduate Research Fellowship DGE1644869 to D.N.T.), and F.C.T. (PD/BD/105819/2014 to D.T.).

G.V.-N. is a co-founder and board director of epiBone, Tara Biosystems, Xylyx Bio, and Immplacate and holds equity in all four companies. K.R-B. and Y.Z. are co-founders of TARA Biosystems and hold equity in the company. S.P.H. holds equity in Xylyx Bio. An.C. is founder, equity holder, and consultant of DarwinHealth, Inc., a company that has licensed some of the algorithms used in this manuscript from Columbia University.

Columbia University is also an equity holder in DarwinHealth Inc. The other authors declare no competing interests.

Nature Biomedical Engineering

A multi-organ chip with matured tissue niches linked by vascular flow

27-Apr-2022

G.V.-N. is a co-founder and board director of epiBone, Tara Biosystems, Xylyx Bio, and Immplacate and holds equity in all four companies. K.R-B. and Y.Z. are co-founders of TARA Biosystems and hold equity in the company. S.P.H. holds equity in Xylyx Bio. An.C. is founder, equity holder, and consultant of DarwinHealth, Inc., a company that has licensed some of the algorithms used in this manuscript from Columbia University.Columbia University is also an equity holder in DarwinHealth Inc. The other authors declare no competing interests.

Continue reading here:
Plug-and-play organ-on-a-chip can be customized to the patient - EurekAlert

Knee and shoulder pain are common complaints for patients in the primary care office.

But identifying the source of the pain can be complicated, and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.

Speaking at the 2022 American College of Physicians Internal Medicine Meeting, Greg Nakamoto, MD, Department of Orthopedics, Virginia Mason Medical Center, Seattle, Washington, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.

The most common conditions causing knee pain are osteoarthritis and meniscal tears. "The differential for knee pain is broad," Nakamoto said. "You have to have a way to divide it down, such as if it's acute or chronic."

The initial workup has several key components. The first steps: Determine the location of the pain anterior, medial, lateral, posterior and then whether it stems from an injury or is atraumatic.

"If you have to ask one question ask where it hurts," he said. "And is it from an injury or just wear and tear. That helps me when deciding if surgery is needed."

Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. "This also helps establish whether radiographic findings are due to injury or degeneration," Nakamoto said. "The presence of swelling guides the need for antiinflammatories or cortisone."

Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Nakamoto said.

"Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint line pain, is suggestive of pain from meniscal pathology," he said.

Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.

Nakamoto offered the following scenario: If significant osteoarthritis is evident on weightbearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.

An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.

An MRI would be ordered later if the patient's symptoms have not improved significantly after three months of conservative management.

Nakamoto stressed how common undiagnosed meniscus tears are in the general population.A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. "That number goes up to 56% and 51% in men and women aged 70 to 90 years, and 61% of these tears were in patients who were asymptomatic in the last month."

In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.

Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.

Three types of injections also can help:

Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation

Viscosupplementation (intraarticular hyaluronic acid) for chronic, baseline osteoarthritis symptoms

Regenerative therapies (platelet-rich plasma, stem cells, etc) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain)

The data on injections are mixed, Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 46 weeks, and small to none at 13 weeks.

"There is a lot of controversy for viscosupplementation despite all of the data on it," he said. "But the recommendations from professional organizations are mixed."

He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.

The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.

As with knee pain, the same assessment routine largely applies.

First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or shoulder blade?

Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.

Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.

As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.

MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.

Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9month period.

Surgery may be warranted in some cases, Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.

Office Orthopedics for the Internist: Common Knee and Shoulder Problems. American College of Physicians (ACP-IM) Internal Medicine Meeting 2022. Presented April 29, 2022.

Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape.

For more news, follow Medscape on Facebook, Twitter, Instagram, YouTube, and LinkedIn.

Originally posted here:
'Where Does It Hurt?': Primary Care Tips for Common Ortho Problems - Medscape

Exposure to pollution in all its forms could be making us age faster, according to new research.

Our everyday exposure to UV rays, ozone, cigarette smoke, industrial chemicals, and other pollutants might be even more damaging than weve believed. Such factors can lead to the production of free radicals in our bodies, highly reactive chemical molecules that damage tissues or DNA. A new study from West Virginia University, in collaboration with the University of Minnesota, reports that unrepaired DNA damage incurred from these radicals can cause us to age faster.

From their research on aging and cell damage in animals, the team is confident in the effect pollution could have on these factors in humans.

By the time [a genetically-modified mouse used in the study] is 5 months old, its like a 2-year-old mouse, said EricKelley, associate professor and associate chair of research in the School of Medicines Department of Physiology and Pharmacology.

It has all the symptoms and physical characteristics. It has hearing loss, osteoporosis, renal dysfunction, visual impairment, hypertension, as well as other age-related issues. Its prematurely aged just because it has lost its ability to repair its DNA.

Kelley and his team used genetically modified mice for their study. These animals had the data encoding a certain protein removed from their hematopoietic stem cells, undifferentiated immune cells that later mature into white blood cells. This protein is a key DNA-repairing component in the mammalian body, and without it, the team could observe what effects their ever-decaying DNA strands would cause to the mices cells.

In rough terms, the team explains, a 2-year-old mouse is about as old as a human in their late 70s to early 80s.

These genetically engineered mice showed more markers of senescence (aging), cell damage, and oxidation in their immune cells compared to control mice. However, The damage extended beyond the immune system, with the experimental mice showing aged and damaged cells in organs including the liver and kidneys. This, they note, suggests that unrepaired DNA damage can lead to premature aging throughout an individuals body.

The oxidation damage observed is largely due to the action of free radicals. There are two main ways that free radicals make their way into our bodies. The first is unavoidable oxidative phosphorylation. Its basically what happens after digestion, the step in which food is actually oxidized in our cells to produce energy. Without it, we couldnt be alive. However, pollution can also introduce these bad chemicals.

Chemical pollutants such as smoke from exhaust or cigarettes can lead to the formation of free radicals inside the body through the interactions they have with chemicals and tissues. Additionally, radiation treatments like those used against cancer can transfer energy to the water molecules in our body, which can break apart into free radicals.

Our bodies do have tools on hand to limit the effects of these free radicals, but nowhere near enough to resist the pollution levels were seeing today.

A cigarette has over 10 to the 16th free radicals per puff, just from combusted carbon materials, Kelley said. We have mechanisms in the mitochondria that mop free radicals up for us, but if they become overwhelmed if we have over-nutrition, if we eat too much junk, if we smoke the defense mechanism absolutely cannot keep up.

Furthermore, as we age, these defenses become less and less effective, as our bodies wear out. Eventually, invariably, the oxidants gain the upper hand, the damage they cause starts outweighing our bodies repair capacity. Many of the characteristics associated with aging are caused by this. But, the team proposes, if were exposed to more pollutants, and accumulate a greater level of free radicals in the body, that aging will take place sooner.

I come from an Appalachian background, Kelley said. And, you know, Id go to funerals that were in some old house an in-the-living-room-with-a-casket kind of deal and Id look at people in there, and theyd be 39 or 42 and look like they were 80 because of their occupation and their nutrition.

The impact is less on lifespan and more on healthspan, he adds. If you could get people better access to healthcare, better education, easier ways for them to participate in healthier eating and a healthier lifestyle, then you could improve the overall economic burden on the population of West Virginia and have a much better outcome all the way around.

Although we have a few pharmaceutical options to deal with free radicals, the team says its best to prevent their accumulation in the first place, mainly through lifestyle changes.

The paper An aged immune system drives senescence and ageing of solid organs has been published in the journal Nature.

The rest is here:
Pollution could be sucking the youth out of you, quite literally - ZME Science

2021 ARCS FoundationHonolulu Chapter Scholars

Nineteen University of Hawaii at Mnoa doctoral candidates have been awarded $5,000 Scholar Awards from the ARCS FoundationHonolulu Chapter. The 2021 award recipients are from six UH Mnoa units.

Institute for Astronomy student Erica Molnar Bufanda was named Scholar of the Year. Recipient of a George and Mona Elmore ARCS Award, Bufanda was selected by a panel of scientists for an additional $1,000 prize for submitting the best short video describing her research. She studies the chemical signatures imprinted on comets to determine if a habitable Earth is a common occurrence in solar system development or an anomaly.

ARCS Foundation is a non-profit volunteer group that works to advance science in America by providing unrestricted grants to outstanding U.S. graduate students in STEM fields. The Honolulu chapter has provided more than $2 million to UH graduate students since 1974.

Ryan Dungee received the Columbia Communications ARCSAward. His research lays important groundwork for other astronomers by improving image quality from telescopes using adaptive optics and benchmarking models for determining a stars age.

Khaldoon Ishmael received the Frederick M. Kresser Award. He works on non-invasive monitoring systems that use Doppler radar based on the ground or unmanned aerial vehicles to detect physiological signals, such as breathing and heart rate.

Harrison Togia received the Bretzlaff Foundation Award. He is engineering resilient methods for identifying hazards and adaptations for coastal communities using free access data, open source programming, evolving measures and deep learning.

Maria Constantini received a Maybelle F. Roth ARCS Award in Conservation Biology. She examines microbiome formation in the endangered akikiki honeycreeper to improve captive breeding efforts.

Ana Flores received a Mona and George Elmore ARCS Award. She monitors plant productivity and growth to gauge their response to environmental stress changes through key developmental stages.

Jeffrey Schueler received the H. Keith and Sue Ernst ARCS Award. He tests predictions of quantum mechanics by studying decay properties of B-mesonssub-atomic particles that are unstable and decay in interesting waysgenerated in the international Belle supercollider experiment in Japan.

Jordan Gossett received the Jacqueline Maly ARCS Award. She studies the co-evolution of leafhoppers and their endosymbiotic bacteria, which provide essential nutrients that are not available in the lava tubes where the insects live.

Bryson Nakamoto received a Sarah Ann Martin ARCS Award. He is developing a method for screening materials to fast-track discovery of a hydrogen storage material.

Samantha Pilgrim received a Sarah Ann Martin ARCS Award. She studies the relationship between symmetries that preserve distances and those that can be approximated by symmetries of finite sets, an area of mathematics with potential applications in physics, engineering and materials science.

Manya Singh received a Maybelle F. Roth ARCS Award in Conservation Biology. She wants to know if invasive plants modify the soil and the organisms living in it in ways that impede native plant restoration, and how that will be affected by droughts related to climate change.

Jeremieh Hasley received the Ellen M. Koenig ARCS Award. He employs CRISPR gene editing technology to create a model papaya crop that researchers can use to study gene function in both papaya and slower growing fruit trees.

David Honsberger received the Helen Jones Farrar ARCS Award. He seeks natural parasites and predators of invasive wood-boring insects like the coffee berry borer and the beetle responsible for spreading Rapid Ohia Death, and ways to improve their efficacy as biological control agents.

Kaitlin Driesse Keegan received an Ellen M. Koenig ARCS Award. She is trying to determine if antibodies from infection with the Dengue virus contribute to the congenital defects related to infection from the closely related Zika virus.

Alexandru Sasuclark received the George and Virginia Starbuck ARCS Award. He investigates the role of the micronutrient selenium in development of cells that transmit signals between motor and sensory neurons and the net that surrounds them.

Dillon Dodson received a George and Mona Elmore ARCS Award. He studies droplet clustering, which is related to droplet size and turbulent intensity, to better understand formation of precipitation.

Chiara Ferrari-Wong received the Toby Lee ARCS Award in Earth Sciences. She looks for predicted but yet-to-be detected organic compounds deposited on the Moon by solar winds.

Jessica Perelman received a George and Mona Elmore ARCS Award. She uses acoustic monitors to observe behavior of animals in the water column of a region targeted for deep-sea mining to inform development of marine protections.

Nicholas Ulm received an Ellen M. Koenig ARCS Award. He works on a wave energy buoy inspired by the Hlona blow hole to optimize power production and provide a stable docking station for autonomous ocean-observing research vehicles.

Read more about the 2021 ARCS Scholars.

This recognition is an example of UH Mnoas goal of Enhancing Student Success (PDF), one of four goals identified in the 201525 Strategic Plan (PDF), updated in December 2020.

Here is the original post:
Habitable Earth an anomaly? Awardees of STEM grants study this and more | University of Hawaii System News - UH System Current News