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Engineering mini human hearts to study pregnancy complications and birth defects

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theconversation.com – Brett Volmert, Ph.D. Candidate in Biomedical Engineering, Michigan – 2024-05-10 07:27:31

Organoids can replicate each component of the human heart, from its chambers to its veins.

Yonatan R. Lewis-Israeli et al. 2021/Nature Communications, CC BY-SA

Brett Volmert, Michigan State University; Aitor Aguirre, Michigan State University, and Aleksandra Kostina, Michigan State University

How did your heart form? What triggered your first heartbeat? To this day, the mechanisms of human heart development remain elusive.

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Researchers know the heart is the first organ to fully function in the growing human embryo. It begins as a simple tube that starts to pump blood by the fourth of gestation. By the ninth week, the heart is fully formed. The heart is critical to early development because it provides essential nutrients throughout the developing fetus.

But due to its early formation, the heart is exposed for a long duration to substances a pregnant person might into contact with, such as medications or pollutants. This may be a main reason why congenital heart disease is the most common type of birth defect in people, occurring in over 1 in 100 births worldwide.

Congenital heart defects typically require surgery to correct.

Traditionally, scientists have used animal and cell models to study heart development and disease. However, researchers haven't been able to produce a cure for congenital heart disease in part because these models are unable to capture the complexity of the human heart. Due to ethical limitations, using human embryos for these studies is out of the question.

To help researchers study heart development and complications in pregnancy, our team of biomedical engineers and cardiovascular scientists have spent the past several years trying to create the next best thing: mini human hearts in the lab.

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Human heart organoids

Organoids are complex 3D cellular structures that replicate significant aspects of the structure and function of a specific organ in your body. While organoids are not completely synthetic, functioning organs (yet), they still possess immense power to mimic key aspects of physiology and disease in the lab.

We created our heart organoids using a type of cell called a pluripotent stem cell. Although using these cells in research used to be controversial because they were originally derived from human embryos, this is no longer a concern, as they can be produced from any adult. Pluripotent stem cells have the potential to become any type of cell in the body. This means that cells from nearly any part of your body – typically blood or skin cells – can be turned into your own stem cells to grow your own mini heart.

Grid of 24 microscopy images: the first row showing a slowly growing black sphere-like shape; the middle row a slowly growing red, blue and purple sphere; the bottom row a collection of blue circles surrounded by red

This figure shows the heart organoid developing over 15 days. The top row is light microscope images, while the bottom two rows show two particular proteins highlighted red and blue.

Yonatan R. Lewis-Israeli et al. 2021/Nature Communications, CC BY-SA

By manipulating the ability of pluripotent stem cells to become any type of cell in the body, we guided these cells to become heart cells. The cells were able to self-assemble, replicating the main stages of human heart development during pregnancy. Our heart organoids have blood vessels and all the cell types found in the human heart, such as cardiomyocytes and pacemaker cells, which give them an edge over 2D cellular models. Furthermore, the electrophysiology and bioenergetics of these heart organoids are very similar to human embryonic hearts in ways that animal models aren't.

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Our heart organoids beat like a tiny baby's heart, all while smaller than a grain of rice.

Pregnancy and the fetal heart

One area we're exploring with our heart organoids is maternal and fetal cardiac . Maternal factors such as diabetes, hypertension or even depression can increase the risk of heart disease in newborns. Studying conditions that increase the risk of congenital heart disease can prevent and reduce the incidence of cardiovascular diseases worldwide.

We can mimic these maternal environments and simulate how they influence fetal heart development with heart organoids. For example, we used heart organoids to show that diabetes, a very common , increases the risk of heart disease in embryos. to heart organoids created in healthy conditions, mini hearts exposed to diabetic conditions developed heart abnormalities like those of human fetuses and newborns with diabetic cardiomyopathy.

Our study found that diabetes-related developmental abnormalities of the heart are likely caused by an imbalance of omega-3 fatty acids, the building blocks of cell membranes and signaling molecules. However, dietary supplementation of omega-3 fatty acids could partially restore this imbalance and prevent diabetes-induced congenital heart defects.

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Drug safety during pregnancy

The pregnant people take can have significant health effects on both the parent and the fetus. Medications approved for use during pregnancy are not always safe, since adequate testing is complicated. Ethical concerns limit working with biological material from people, so researchers are left with animal models that aren't able to replicate human physiology closely enough.

Testing medications on human heart organoids allows researchers to better explore and predict potential harmful effects during pregnancy. One example is ondansetron (Zofran), a drug commonly prescribed to prevent nausea and vomiting during pregnancy. Although it has been linked with an increased risk of congenital heart disease, whether it causes the disease hasn't been confirmed.

We showed that heart organoids exposed to ondansetron had disturbed development of ventricular cells and impaired function, similar to what's seen in newborns exposed to ondansetron. Our findings data that may help clinical guidelines on the use of the drug.

Person holding a parckage insert above a blister pack of pills and a glass of water on a counter

Certain medications may increase the risk of congenital heart defects.

Fiordaliso/Moment via Getty Images

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Another example concerns the use of antidepressants during pregnancy, which is associated with an increased risk of congenital heart defects. Selective serotonin reuptake inhibitors, or SSRIs, the most prescribed antidepressants in pregnant people, work by increasing the availability of serotonin in the body. Serotonin is an important molecule in cardiac development. Maternal serotonin, along with antidepressants, readily pass to the embryo and alter serotonin levels in the developing heart.

In the future, we plan to expose heart organoids to antidepressants and study their effects on the incidence of congenital heart defects. The results of such research on human heart organoids may also inform recommendations for drug replacement or repurposing.

Heart organoids have the potential to help scientists more precisely study how the human heart forms and how it develops disease. In the realm of medical innovation, we believe human heart organoids grown from stem cells are the beating promise of a healthier future.The Conversation

Brett Volmert, Ph.D. Candidate in Biomedical Engineering, Michigan State University; Aitor Aguirre, Associate Professor of Biomedical Engineering, Michigan State University, and Aleksandra Kostina, Postdoctoral Researcher in Quantitative Health Sciences and Engineering, Michigan State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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The Conversation

AI chatbots are intruding into online communities where people are trying to connect with other humans

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theconversation.com – Casey Fiesler, Associate Professor of Information Science, University of Colorado Boulder – 2024-05-20 07:27:05

AI chatbots are butting into human spaces.

gmast3r/iStock via Getty Images

Casey Fiesler, University of Colorado Boulder

A parent asked a question in a private Facebook group in April 2024: Does anyone with a child who is both gifted and disabled have any experience with New York public schools? The parent received a seemingly helpful answer that laid out some characteristics of a specific school, beginning with the context that “I have a child who is also 2e,” meaning twice exceptional.

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On a Facebook group for swapping unwanted items near Boston, a user looking for specific items received an offer of a “gently used” Canon camera and an “almost-new portable conditioning unit that I never ended up using.”

Both of these responses were lies. That child does not exist and neither do the camera or air conditioner. The answers came from an artificial intelligence chatbot.

According to a Meta help page, Meta AI will respond to a post in a group if someone explicitly tags it or if someone “asks a question in a post and no one responds within an hour.” The feature is not yet available in all regions or for all groups, according to the page. For groups where it is available, “admins can turn it off and back on at any time.”

Meta AI has also been integrated into search features on Facebook and Instagram, and users cannot turn it off.

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As a researcher who studies both online communities and AI ethics, I find the idea of uninvited chatbots answering questions in Facebook groups to be dystopian for a number of reasons, starting with the fact that online communities are for people.

Human connections

In 1993, Howard Rheingold published the book “The Virtual Community: Homesteading on the Electronic Frontier” about the WELL, an early and culturally significant online community. The first chapter opens with a parenting question: What to do about a “blood-bloated thing sucking on our baby's scalp.”

Rheingold received an answer from someone with firsthand knowledge of dealing with ticks and had resolved the problem before receiving a callback from the pediatrician's office. Of this experience, he wrote, “What amazed me wasn't just the speed with which we obtained precisely the information we needed to know, right when we needed to know it. It was also the immense inner sense of security that comes with discovering that real people – most of them , some of them nurses, doctors, and midwives – are available, around the clock, if you need them.”

This “real people” aspect of online communities continues to be critical . Imagine why you might pose a question to a Facebook group rather than a search engine: because you want an answer from someone with real, lived experience or you want the human response that your question might elicit – sympathy, outrage, commiseration – or both.

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Decades of research suggests that the human component of online communities is what makes them so valuable for both information-seeking and social support. For example, fathers who might otherwise feel uncomfortable asking for parenting advice have found a haven in private online spaces just for dads. LGBTQ+ youth often join online communities to safely find critical resources while reducing feelings of isolation. Mental health support forums provide young people with belonging and validation in addition to advice and social support.

Online communities are well-documented places of support for LGBTQ+ people.

In addition to similar findings in my own lab related to LGBTQ+ participants in online communities, as well as Black Twitter, two more recent studies, not yet peer-reviewed, have emphasized the importance of the human aspects of information-seeking in online communities.

One, led by PhD student Blakeley Payne, focuses on fat people's experiences online. Many of our participants found a lifeline in access to an audience and community with similar experiences as they sought and shared information about topics such as navigating hostile , finding clothing and dealing with cultural biases and stereotypes.

Another, led by Ph.D student Faye Kollig, found that people who share content online about their chronic illnesses are motivated by the sense of community that comes with shared experiences, as well as the humanizing aspects of connecting with others to both seek and provide support and information.

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Faux people

The most important of these online spaces as described by our participants could be drastically undermined by responses coming from chatbots instead of people.

As a type 1 diabetic, I follow a number of related Facebook groups that are frequented by many parents newly navigating the challenges of caring for a young child with diabetes. Questions are frequent: “What does this mean?” “How should I handle this?” “What are your experiences with this?” Answers from firsthand experience, but they also typically come with compassion: “This is hard.” “You're doing your best.” And of course: “We've all been there.”

A response from a chatbot to speak from the lived experience of caring for a diabetic child, offering empathy, would not only be inappropriate, but it would be borderline cruel.

However, it makes complete sense that these are the types of responses that a chatbot would offer. Large language models, simplistically, function more similarly to autocomplete than they do to search engines. For a model trained on the millions and millions of posts and comments in Facebook groups, the “autocomplete” answer to a question in a support community is definitely one that invokes personal experience and offers empathy – just as the “autocomplete” answer in a Buy Nothing Facebook group might be to offer someone a gently used camera.

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Meta has rolled out an AI assistant across its social media and messaging apps.

Keeping chatbots in their lanes

This isn't to suggest that chatbots aren't useful for anything – they may even be quite useful in some online communities, in some contexts. The problem is that in the midst of the current generative AI rush, there is a tendency to think that chatbots can and should do everything.

There are plenty of downsides to using large language models as information retrieval systems, and these downsides point to inappropriate contexts for their use. One downside is when incorrect information could be dangerous: an eating disorder helpline or legal advice for small businesses, for example.

Research is pointing to important considerations in how and when to design and deploy chatbots. For example, one recently published paper at a large human-computer interaction conference found that though LGBTQ+ individuals lacking social support were sometimes turning to chatbots for with mental health needs, those chatbots frequently fell short in grasping the nuance of LGBTQ+-specific challenges.

Another found that though a group of autistic participants found value in interacting with a chatbot for social communication advice, that chatbot was also dispensing questionable advice. And yet another found that though a chatbot was helpful as a preconsultation tool in a health context, patients sometimes found expressions of empathy to be insincere or offensive.

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Responsible AI development and deployment means not only auditing for issues such as bias and misinformation, but also taking the time to understand in which contexts AI is appropriate and desirable for the humans who will be interacting with them. Right now, many companies are wielding generative AI as a hammer, and as a result, everything looks like a nail.

Many contexts, such as online support communities, are best left to humans.The Conversation

Casey Fiesler, Associate Professor of Information Science, University of Colorado Boulder

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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The Conversation

Is hard water bad for you? 2 water quality engineers explain the potential benefits and pitfalls that come with having hard water

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theconversation.com – Sarah Blank, Master's Student in Civil Engineering, Iowa – 2024-05-20 07:26:46

Do you know how hard your is?

Tatiana Maksimova/Moment via Getty Images

Sarah Blank, Iowa State University and Timothy Ellis, Iowa State University

When you turn on your faucet to get a glass of water or wash your face, you're probably not thinking about what's in your water – besides water. Depending on where you live and whether you have a water-softening system, your water might contain dissolved minerals such as calcium and magnesium. And these minerals can play a role in whether certain pollutants such as lead stay out of your water.

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The more dissolved minerals, the “harder” your water. But is hard water actually good or bad for you?

As engineering researchers who study water quality, we have seen the effects – both good and bad – that soft and hard water can have on everything from plumbing systems to the human body.

What is hard water?

Hard water is water that contains dissolved minerals such as calcium, magnesium, iron and manganese. Soft water contains lower concentrations of these minerals.

Hardness is measured in terms of calcium carbonate, CaCO₃, which is used as a reference point for comparing different minerals.

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The amount of these minerals in a 's water supply varies by region. It depends on both where the water is coming from and how the water is treated.

Communities that source their water from wells rather than surface water such as lakes, streams, rivers and reservoirs often start with hard water pretreatment. As groundwater moves through the soil to a well, it picks up minerals. At the same time, areas where the types of rock and sediment are more prone to dissolving in water may have harder water.

A map showing water hardness across the U.S., with the hardest water in the Midwest, West and Southwest.

Streamflow water hardness across the U.S., where purple and blue indicate softer water and white and red indicate harder water. This map was updated in 2005 by the U.S. EPA.

U.S. Geological Survey

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Effects on water lines and distribution

Water that's too hard or too soft could damage pipes and lead to health and aesthetic concerns.

Since hard water has a higher mineral concentration, minerals can build up in pipes, which to clogged pipes in homes and public water systems. Hardness also creates more deposits at higher temperatures, so hot water heaters are prone to mineral buildup. In areas with hard water, water heaters have a shorter span.

A pipe with gray material around the inside.

A pipe that has a thick layer of mineral deposits inside of it.

Mevedech/Wikimedia Commons

But hard water can help, too. While minerals from hard water can clog pipes, a thin layer of mineral deposition in water lines can protect you from ingesting toxins that could seep in from the pipe itself. Water without any minerals can play a role in pipe corrosion, because without a thin, protective layer of minerals, the water may start to eat away at the pipes, releasing metals from the pipes into the water. Drinking this water might mean ingesting metals such as lead, copper and iron.

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While water that is too soft or too hard can have different effects on water lines, there is more chemistry than just hardness that plays a role in pipe corrosion and clogging. So, there's no specific hardness level that is a cause for concern. Water treatment plants take the appropriate measures to adjust for different hardness levels.

A large tank of water, with fences around the top.

Drinking water normally undergoes treatment at a plant before it makes its way to your home.

Florida Water Daily, CC BY

Effects on skin and hair

Whether you use hard or soft water to wash up can also have noticeable effects on your skin and hair.

Hard water is more likely to leave your skin dry. The minerals in hard water strip moisture from skin and create deposits that clog pores.

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Hard water can also strip the hair of moisture, leaving it dry and coarse. Dry hair is more prone to frizz, tangles and breakage. Mineral deposits can also build up on the hair and scalp, clogging your hair follicles and leading to dandruff and slowed hair growth.

Many households have their own water-softening systems. A water-softening system may help hair and skin dryness and buildup. But many of these systems trap and replace calcium and magnesium with sodium, a mineral that does not contribute to water hardness, to lower overall hardness. Increasing the water's sodium content may be a concern for anyone on a low-sodium diet.

Overall health benefits

Other than aesthetic and water heater concerns, drinking hard water is actually good for you and doesn't with any serious adverse side effects.

For example, the extra magnesium and calcium you consume in hard water may provide a gentle solution to digestive issues and constipation.

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Also, researchers have found positive correlations between the hardness of drinking water and bone health. Since calcium is an essential mineral in bones, individuals in areas with drinking water that has more calcium may have higher bone mineral density and may be less prone to osteoporosis.

Researchers have also found that drinking hard water has been associated with a decrease in cardiovascular disease-related mortality. Magnesium helps regulate your cardiac muscles, while calcium keeps the sodium-potassium balance in your cardiac muscles in check, which they need to function.

Whether you have hard or soft water, don't worry too much. Water treatment plants take appropriate measures to ensure safe water for the communities they .

To learn more about the water hardness in your area, you can contact your local water treatment plant about its specific water treatment . Private well owners can contact their state to find out the testing recommendations for their area.The Conversation

Sarah Blank, Master's Student in Civil Engineering, Iowa State University and Timothy Ellis, Associate Professor of Civil, Construction and Environmental Engineering, Iowa State University

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This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Black holes are mysterious, yet also deceptively simple − a new space mission may help physicists answer hairy questions about these astronomical objects

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theconversation.com – Gaurav Khanna, Professor of Physics, of Rhode Island – 2024-05-15 07:16:18

An illustration of a supermassive black hole.

NASA/JPL

Gaurav Khanna, University of Rhode Island

Physicists consider black holes one of the most mysterious objects that exist. Ironically, they're also considered one of the simplest. For years, physicists like me have been looking to prove that black holes are more complex than they seem. And a newly approved European space mission called LISA will us with this hunt.

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Research from the 1970s suggests that you can comprehensively describe a black hole using only three physical attributes – their mass, charge and spin. All the other properties of these massive dying , like their detailed composition, density and temperature profiles, disappear as they transform into a black hole. That is how simple they are.

The idea that black holes have only three attributes is called the “no-hair” theorem, implying that they don't have any “hairy” details that make them complicated.

Black holes are massive, mysterious astronomical objects.

Hairy black holes?

For decades, researchers in the astrophysics community have exploited loopholes or work-arounds within the no-hair theorem's assumptions to up with potential hairy black hole scenarios. A hairy black hole has a physical property that scientists can measure – in principle – that's beyond its mass, charge or spin. This property has to be a permanent part of its structure.

About a decade ago, Stefanos Aretakis, a physicist currently at the University of Toronto, showed mathematically that a black hole containing the maximum charge it could hold – called an extremal charged black hole – would develop “hair” at its horizon. A black hole's horizon is the boundary where anything that crosses it, even light, can't escape.

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Aretakis' analysis was more of a thought experiment using a highly simplified physical scenario, so it's not something scientists expect to observe astrophysically. But supercharged black holes might not be the only kind that could have hair.

Since astrophysical objects such as stars and planets are known to spin, scientists expect that black holes would spin as well, based on how they form. Astronomical evidence has shown that black holes do have spin, though researchers don't know what the typical spin value is for an astrophysical black hole.

Using computer simulations, my team has recently discovered similar types of hair in black holes that are spinning at the maximum rate. This hair has to do with the rate of change, or the gradient, of -time's curvature at the horizon. We also discovered that a black hole wouldn't actually have to be maximally spinning to have hair, which is significant because these maximally spinning black holes probably don't form in nature.

Detecting and measuring hair

My team wanted to develop a way to potentially measure this hair – a new fixed property that might characterize a black hole beyond its mass, spin and charge. We started looking into how such a new property might a signature on a gravitational wave emitted from a fast-spinning black hole.

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A gravitational wave is a tiny disturbance in space-time typically caused by violent astrophysical in the universe. The collisions of compact astrophysical objects such as black holes and neutron stars emit strong gravitational waves. An international network of gravitational observatories, the Laser Interferometer Gravitational-wave Observatory in the United States, routinely detects these waves.

Our recent studies suggest that one can measure these hairy attributes from gravitational wave data for fast-spinning black holes. Looking at the gravitational wave data offers an for a signature of sorts that could indicate whether the black hole has this type of hair.

Our ongoing studies and recent progress made by Som Bishoyi, a student on the team, are based on a blend of theoretical and computational models of fast-spinning black holes. Our findings have not been tested in the field yet or observed in real black holes out in space. But we hope that will soon change.

LISA gets a go-ahead

In January 2024, the European Space Agency formally adopted the space-based Laser Interferometer Space Antenna, or LISA, mission. LISA will look for gravitational waves, and the data from the mission could help my team with our hairy black hole questions.

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Three spacecrafts spaced apart sending light beams towards each other while orbiting the Sun

The LISA spacecrafts observing gravitational waves from a distant source while orbiting the Sun.

Simon Barke/Univ. Florida, CC BY

Formal adoption means that the has the go-ahead to move to the construction phase, with a planned 2035 launch. LISA consists of three spacecrafts configured in a perfect equilateral triangle that will trail behind the Earth around the Sun. The spacecrafts will each be 1.6 million miles (2.5 million kilometers) apart, and they will exchange laser beams to measure the distance between each other down to about a billionth of an inch.

LISA will detect gravitational waves from supermassive black holes that are millions or even billions of times more massive than our Sun. It will build a map of the space-time around rotating black holes, which will help physicists understand how gravity works in the close vicinity of black holes to an unprecedented level of accuracy. Physicists hope that LISA will also be able to measure any hairy attributes that black holes might have.

With LIGO making new observations every day and LISA to offer a glimpse into the space-time around black holes, now is one of the most exciting times to be a black hole physicist.The Conversation

Gaurav Khanna, Professor of Physics, University of Rhode Island

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