Embryology

The Lawmakers Behind Fetal Heartbeat Abortion Bans Are Lying To You – HuffPost

Its been two years since conservative lawmakers began widely using fetal heartbeat rhetoric to pass bans on abortion as early as six weeks into pregnancy.

But despite the medical community speaking out against the inaccurate language and dozens of lawsuits stopping those laws from going into effect, those bills havent slowed down. The latest comes from Texas, where Gov. Greg Abbott (R) signed a bill Wednesday effectively banning abortions as soon as a doctor can detect cardiac activity in an embryo, which typically happens at around six weeks into a pregnancy.

But doctors say that not only is that cutoff completely arbitrary, its also based on the false premise that a fetal heartbeat a phrase often included in the bills titles even exists at that stage of pregnancy.

To say that a six-week pregnancy has a fetal anything is incorrect, explained Dr. Colleen McNicholas, an obstetrician-gynecologist who performs abortions, noting that the term fetal heartbeat isnt even applicable until about 10 weeks into a pregnancy. At that point, an embryo has developed sufficiently to be called a fetus.

At six weeks, an embryos cardiac development doesnt at all resemble what would eventually become a functioning human adult heart, she said. At that point, it really is just these two tubes with a couple of layers of cardiac or heart cells that can vibrate or cause some sort of movement that we use colloquially to talk about a fetal heartbeat.

McNicholas is based in St. Louis, Missouri, where an appeals court is currently weighing one of the laws signed in 2019.

Governors in South Carolina, Oklahoma and Idaho have all signed similar bills similar to the one in Texas this year. However, they, too, are tied up by legal challenges.

Elijah Nouvelage via Getty ImagesPeople in Atlanta protest against Georgia's six-week abortion ban in 2019.

Dr. Carley Zeal, another OB-GYN based in St. Louis, expressed similar frustration with the fetal heartbeat terminology these bills are using.

An embryo at six weeks has no other functioning organs, no ability to live on its own, and its actually so small that when we review pathology from an abortion or a miscarriage at six weeks gestation, theres not an identifiable fetus to review, she said. Its just a gestational sac and some cells, so its very small and definitely not able to live outside of the womb.

At that point, an embryo is less than a centimeter long, she said. Thats smaller than a penny or the width of most peoples pinky fingers.

But the way the lawmakers orchestrating these abortion bans speak about pregnancy at that stage leaves a very different impression.

If there is a detection of a heartbeat, that child is a living human being, and you can no longer murder this child in its mothers womb, Kentucky state Sen. Matt Castlen (R) said at a press conference when introducing his states fetal heartbeat bill in 2019.

What were doing is ... recognizing that the child with a beating heart inside of mom thats got a heartbeat, that theyre preparing a nursery for, that is wiggling around inside mom, is actually a person,Georgia state Rep. Ed Setzler (R), the architect behind his states abortion ban, alsosaidthat year.

Science tells us that the heartbeat really is the beginning of life and the end of life, he added.

Science doesnt actually tell us that, said Zeal, who testified against the Missouri bill as part of her involvement with the group Physicians for Reproductive Health. The focus on the heartbeat as a cutoff date is completely arbitrary.

Theres a lot of talk from the other side about a heartbeat being the point at which a life begins, which is really based on their ideologies, she said. What we are trying to focus on as providers is to take it away from their black-and-white ideology and focus back on what is safest and what is the most effective care for our patients.

McNicholas agreed. From a medical standpoint, there is no single organ that we say defines life, she said.

To her, focusing on the heart is taking advantage of one of societys most deep-seated word associations. The heart is merely a muscle that pumps blood through someones circulatory system, but idioms like following your heart and a broken heart have given anti-abortion activists something that tugs at peoples heartstrings figuratively speaking.

I think that its a capitalization on our societys longstanding obsession and infatuation around the symbolism of the heart, she said. We use the heart visually in so many different ways to mean so many different things, and I think this particular approach really capitalizes on our obsession with the heart being a symbol of something.

Beyond lawmakers ignoring facts about embryology, theyre disregarding a huge practical issue: Many patients dont know theyre pregnant in the first six to eight weeks of pregnancy, both doctors said. Its common for patients who have irregular periods, thyroid issues, financial insecurities that limit their medical access and other atypical circumstances to miss or not have any early signs of pregnancy.

SOPA Images via Getty ImagesA demonstrator in Columbia, South Carolina, in February holds up a sign in favor of the state's six-week abortion ban.

But lawmakers supporting those bills are dismissing those common circumstances. Missouri state Rep. Barry Hovis (R) argued in 2019 that under his states bill, which estimated that a fetal heartbeat can be detected at eight weeks instead of six, patients would still have plenty of time to seek out an abortion.

Ive never really studied it, but Ive heard of the morning-after pill, where if someone feels theyve been sexually assaulted, they could go do that, he said at the bills final hearing. It gives them ample time in that eight weeks to make those exclusions.

We shouldnt give lawmakers a pass to play dumb, Zeal said.

Make no mistake, these bans are designed to ban almost all abortion, she emphasized. Legislators writing these bans understand that this would make almost all abortions that we do illegal and make it completely inaccessible to patients, and thats why theyre trying to get them through. Its not at all based on a womans health or a fetus health.

Although abortion remains legal in all 50 states, a serious threat to that looms. The Supreme Court announcedMonday that it would take up a case addressing whether all pre-viability prohibitions on elective abortions are unconstitutional a question that not only addresses six-week bans, but also outright bans governors in Alabama and Arkansas have tried to enact.

This is the first time the court has agreed to review an abortion ban since deciding Roe v. Wade in 1973, which has protected access to the procedure for 48 years.If the court reshaped into a firmly conservative body by former President Donald Trump decides in favor of such bans, the protections established in Roe v. Wade would be essentially tossed out.Twenty-four states hostile to the procedure would likely ban abortion outright, abortion rights activists warn.

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Physiology

New method shows that tau forms small aggregates as part of the body’s normal physiology – News-Medical.Net

It turns out that not all build-ups of tau protein are bad, and a team of researchers from the Perelman School of Medicine at the University of Pennsylvania developed a method to show that. Using mammalian cell models, the researchers combined extremely high-resolution microscopy with machine learning to show that tau actually forms small aggregates as a part of the body's normal physiology.

Through this, they could distinguish between the aggregates occurring under healthy conditions from the ones associated with neurological diseases, potentially opening the door to screening for treatments that might break apart harmful aggregates. This research was published in the Proceedings of the National Academy of Sciences of the United States of America.

"There aren't many tools that can visualize small, pathological protein aggregates within cells," said the study's senior author, Melike Lakadamyali, PhD, an associate professor of Physiology. "But through machine learning informed by super-resolution microscopy, we believe we've been able to show that tau forms both normal physiological aggregates and distinct pathological aggregates. In doing so, we created a useful method that could be the basis for new research into the appropriate treatments for tau-related pathologies."

Tau is a protein that attaches to the microtubule structure of axons - which act much like highways in nerve cells. Previously, tau aggregates had been thought to only form once tau falls off the microtubules. These have been associated with some neurological diseases, including Alzheimer's and other types of dementia. However, it turns out that small tau aggregates can also form outside disease conditions.

Intrinsically, there is value in being able to tell which tau aggregates are a part of a healthy person's nervous system, and which have formed harmful aggregates. Unfortunately, there has not been a process sensitive enough to make that distinction yet inside cells. So we set out to create one using mammalian cell models."

Melina Theoni Gyparaki, Study Lead Author adn Doctoral Student in Lakadamyali's Lab

First, the researchers used extremely high resolution microscopes capable of looking at single molecules to differentiate physiological and pathological oligomers (molecular formations). Monomers, dimers and trimers, which are oligomers made up of one, two, and three tau molecules, respectively, were most likely to end up associated with healthy physiological conditions because they were associated with microtubules and regular function.

When the team looked at tau structures associated with a mammalian cell model approximating frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) - a disease associated with tau aggregation - the structures were larger and more complex. These appeared to be the pathological tau aggregates that broke off.

With the differences in configuration established, the researchers created a machine learning algorithm to classify the pathological tau aggregates by shape alone. Additionally, they used antibodies that can detect and differentiate when the tau aggregates become "hyper-phosphorylated" - when they pick up a lot of phosphate groups and tend to harmfully break off. Combining these methods showed that tau containing phosphate groups on certain amino-acids was more likely to form linear fibrils, a thin structure, as opposed to other shapes of tau aggregates.

"The method we developed to identify tau aggregates is not yet a diagnostic tool, but we think it would be a useful research tool for anyone interested in studying the mechanisms that lead to pathological protein oligomerization in neurodegenerative disease," Lakadamyali said.

Tau aggregates aren't the only ones that this method could be used to classify, either. There's an opportunity to use it on other potentially pathological protein build-ups, such as alpha-synuclein, which is associated with Parkinson's disease, or huntingtin, related to Huntington's disease. It could also be used to screen for potential treatments for these conditions that don't harm the body's regular protein complexes.

The team is now studying potential mechanisms for clearing tau aggregates and determining what other pathways could be helpful in this regard.

"We are also further using the method we devised to visualize tau aggregates in human postmortem brain tissue slices from Alzheimer's disease to determine the role of tau's post-translational modifications in aggregation," Lakadamyali said.

Source:

Journal reference:

Gyparaki, M. T., et al. (2021) Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2021461118.

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New method shows that tau forms small aggregates as part of the body's normal physiology - News-Medical.Net

Physiology

Bizarre ‘stomach’ case put Plattsburgh on the map – Plattsburgh Press Republican

PLATTBURGH -- French-Canadian Alexis St. Martin returned several times to the United States, where hundreds of physiological experiments were conducted on him by Dr. William Beaumont,The Father of Gastric Physiology.

CUTTING-EDGE RESEARCH

In 1833, Beaumont's notes and drawings were consolidated in a book, Experiments and Observations of the Gastric Juice and the Physiology of Digestion published by by F. P. Allen, a local newspaper publisher in Plattsburgh.

The book was later published in Great Britain, France, Germany and Scotland.

Dr. Paolo Fedi of Beaumont Gastroenterology Services was able to secure a first-edition copy of the rare tome.

The book was poorly published because this was a newspaper, Fedi said.

It was not a publication that was done in a bound book. Beaumont never used any of the important universities at that time. He never connected with them. So this book, a few copies remained.

Medical interest surged in Beaumont's research and his study of St. Martin.

Everybody wanted him to come to their place, but this guy refused to connect further, Fedi said.

He went into Canada and disappeared from any public venue. He didn't want to have anything anymore.

SUCCESSFUL PRACTICE

St. Martin would not meet in St. Louis with Beaumont, whowas stationed there in 1830 and was appointed Surgeon at Jefferson Barrack and later the Arsenal.

About 1835, he took up his residence in St. Louis and two or three years later he resigned from the Army and took up private practice, according to his obituary.

Beaumont lived in St. Louis 19 years, where he was appointed Professor of Surgery at Saint Louis University's Medical Department.

He died (April 25, 1853) after a slip on the ice while he was going to see a patient, Fedi said.

Beaumont is buried in Bellefontaine Cemetery in St. Louis as his wife, Deborah Greene Beaumont (1799-1870) and their daughter, Sarah Beaumont Keim (1825-1913).

Their son, Israel Greene Beaumont (1829-1901 is buried in the Woodlawn Cemetery in Green Bay, Wisconsin.

Living in Plattsburgh here, he had an office where the store that is now called Ashley Furniture is, Fedi said.

He had an office and practice there. There is a plaque there that was placed by the Medical Society, I think in the '70s.

After his publication, he was able to determine that the stomach is able to digest food because it produces acid. They called it at the time muratic acid. Now, it's what is called hydrochloric acid. Before that we did not know the stomach was producing acid. The science at the time held food sat or putrefied in the stomach.

Beaumont's experiments with St. Martin proved and demonstrated otherwise.

That made an explosion of research everywhere, Fedi said.

His work was really fundamental to the understanding of the digestion of the GI tract.

He was a great observer. He was able to kind of look at the stomach and he realized that the weather, the stress of different things was able to affect the stomach of the GI tract, illnesses.

So when Alexis was drinking too much, they were able to see that his stomach wasn't really healthy, and it was taking much longer to digest than what was normal.

The pioneering medical researcher also noticed similar outcomes for the effects of tobacco on the stomach.

Beaumont put Plattsburgh on the map for medical history because at that time there was not really major hospital or any other things here, Fedi said.

Because of the Army base and him, it became an important site.

PARTED WAYS

St. Martin, born April 8, 1802 in Berthierville, Quebec, died June 24, 1880 in Saint-Thomas de Joilette in Quebec.

The wood chopper fathered 22 children, and his burial site remained secret until 1962.

He was so worried that somebody would come and get even when he was dead, he left a will that stated his body should be left to decompose for four or five days before he was put in the ground and one should know where the body would be, Fedi said.

Alexis Bidagan dit St-Martin is buried at St. Thomas Parish Cemetery in Joliette, Quebec.

A great-niece of his made it public that he was actually buried in the cemetery of a specific church, so they were able to put a tombstone with his name and other things," Fedi said.

"It is just outside of Montreal.

Beaumont name's graces the Beaumont Hall Science Building at SUNY Plattsburgh, the William Beaumont Army Medical Center in El Paso, Texas, and the largest health care system in Michigan.

It's still amazing that many people do not know anything about this history, Fedi said.

I have medical practice called Beaumont. Many people are like 'You're Italian, why do you use this French name?'

I love history. I'm fascinated with the idea that I can use his name for a practice of the GI tract.

Email Robin Caudell:

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Twitter:@Robin Caudell

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Bizarre 'stomach' case put Plattsburgh on the map - Plattsburgh Press Republican

Physiology

Luke Heckmann, UT21 Senior – UT News – UT News | The University of Texas at Austin

Going up to the hives was always a thrilling, but also exhaustingly hot, experience, Heckmann says. We would wear those big white beekeeper suits with the meshed veil to protect ourselves, and we would use smoke canisters to get the bees to fly into the hive and make it simpler to open and remove frames.

As an undergraduate, Heckmann was part of the Moran Lab, which was investigating ways to protect honeybee health for thriving ecosystems. Researchers focused on studying a particular species of bacteria living within the bees guts.

While working directly with and gathering data from the bees, Heckmann edited circular rings of bacterial DNA known as plasmids. Ultimately, Heckmann and the group discovered a way to genetically modify that gut bacteria to enable the cells of bees to fight off deadly viruses and mites.

It was his biggest and proudest accomplishment yet, taking multiple years of work and an enormous number of hours from many different people, Heckmann says. So it was just a huge, huge achievement for all of us really after so many years.

Later, Heckmann even received funding from a Undergraduate Research Fellowship to further expand upon that research. And even after COVID-19 hit, he was able to continue that work remotely.

Research has formed his undergraduate experience, but Heckmann says his ultimate goal is to become a doctor. Never boxed in, he actually aspired to be an engineer growing up. He was always interested in the mechanics and moving parts of anything and everything, but in high school, Heckmann took a transformative anatomy and physiology course, opening his eyes to a future in medicine.

It wasnt until that anatomy class I took, where I really started seeing things from a different perspective. You sort of see that the body is almost like the most finely tuned machine, Heckmann says.

Heckmann, born in Oklahoma but basically an Austin native after having moved here when he was 2, says it was a no-brainer applying and committing to UT Austin for its academic rigor and great location. Upon arrival, he quickly combined his interests in engineering and the natural sciences to pursue biomedical engineering.

Heckmann says some of his favorite courses were Organic Chemistry I and II, which focused on studying carbon, the building block of life, and Tumor Biology, which investigated core aspects of cancer pathology, treatment and epidemiology with molecular biosciences professor Jon Huibregtse.

Glancing over at a whiteboard in his room, he says it is filled with notes from that course. I still have a bunch of diagrams because theyre just so satisfying to look at, he says, laughing. That class was incredible and really pertinent because cancer is unfortunately so common.

As a graduating senior, Heckmann cannot recommend doing research as an undergraduate enough. Id honestly encourage everyone to try and seek out a research opportunity. He says: I learned a ton from conducting research and being a part of a lab and a group of people, or a community, if you will. A lot of things I learned in the lab werent even research-related, but just related to life in general.

Looking past graduation, Heckmann is ready to bring his skills to medical school. The great thing about UT is that it does a really good job at equipping us with different skills and different opportunities that are life-lasting. When experiments fail, I had to adapt over and over again in the face of new information, and that adaptability will be vital for me as a future physician.

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Physiology

The Answer to the Andorians Blue Skin is in Their Blood – Heavy.com

YouTubeAndorians from "Star Trek: Enterprise"

The blue-skinned Andorians are one of the most distinctive species in the Star Trek universe. Though the appearance of the species has changed significantly from show to show, a few characteristics have remained consistent. Andorians have small forehead ridges, a pair of antennae, white hair and bright blue skin.

The Andorians were first introduced in the episode Journey to Babel from Star Trek: The Original Series. Veteran Star Trek writer Dorothy Fontana created the species specifically for the episode.

Her original notes revealed little about the species, though they did reveal why they were blue. However, her explanation is very different than the reason that became part of the Star Trek canon.

Albert L. Ortega / Getty Images

When Star Trek was brand new in the 1960s, the writers got the opportunity to create new species all the time. Each of the different species that fans are familiar with today was created from scratch by the writers. In fact, many of them were created by Fontana herself.

Often, these new species were born from an interesting concept or makeup idea. This was the case with the Andorians.

A makeup and costume memo Fontana wrote for Journey to Babel stated, Andorians are pale blue. Because.

Fontana didnt include much more information about the Andorian physiology, other than their antennae, or provide a further reason for their distinctive appearance. Few details were included about their culture either, with the exception of the fact that they were fierce warriors.

For decades, the Andorians were rarely seen in Star Trek shows. They made a couple of appearances in Star Trek: The Animated Series and Star Trek: The Next Generation but were completely absent from both Star Trek: Deep Space Nine and Star Trek: Voyager.One likely reason for the lack of Andorians was the complicated makeup, which was both costly and time-consuming.

Because the Andorians appeared so rarely, there werent any opportunities to learn about their physiology or culture until Star Trek: Enterprise. Showrunners Rick Berman and Brannon Braga decided that they wanted to bring the Andorians back in the prequel show and make them a major part of the series. They worked with the visual effects department to completely redesign the makeup and antennae. The result was a much more believable and striking species.

Bringing the Andorians back also meant expanding their backstory and making them a more complex species. According to The Fifty-Year Mission: The Next 25 Years, the Enterprise writing staff, with Fred Dekker taking the creative lead, was tasked with creating all the details about the Andorians that were left out of the previous series. They fleshed out the Andorian physiology, psychology, and culture episode by episode.

In one of the Andorian-centric episodes, United, the Andorians blue skin was finally given a canonical explanation. During that episode, Lieutenant Talas was fatally wounded. The blood from her wounds was the same shade of blue as her skin. This suggests that the Andorians skin is somewhat translucent, allowing the pigment of the blood to show through.

This canonical explanation doesnt fit with the physiology of other alien species in the Trekverse. The Vulcans and Romulans have green blood, but their skin doesnt reflect the color of their blood. Klingons usually have red blood, though in Star Trek VI: The Undiscovered Country, they inexplicably have pink blood. Klingon skin color is almost always brown, with the exception of the Albino in DS9 and the albinos in Star Trek: Discovery. So, their skin doesnt reflect their blood color either.

In humans, skin color has nothing to do with the color of the blood. According to the Smithsonian, human pigmentation is the result of melanin. The more melanin, the darker the skin, the less melanin the lighter the skin. Since Vulcans, Romulans, and Klingons all have skin colors that have nothing to do with the color of their blood, it follows that their skin color is the result of an alien equivalent of melanin. If the Andorians really do get the color of their skin from their blood, it follows that their skin doesnt have its own pigmentation.

However, this explanation doesnt even make sense within the canon created by Enterprise. In the episode The Aenar, a subspecies of Andorians called Aenar were discovered by Shran and Archer. They were considered a myth by most Andorians since they were isolated to the harshest environments of the planet.

The Aenar have white skin with just a hint of blue in it. They were described as albino Andorians, which implies that their skin lacked pigmentation entirely. Since the Aenar evolved from the Andorians, this suggests that the Andorians do, in fact, have pigmented skin. So, the color of their blood shouldnt impact the color of their skin.

Whether it makes sense or not, the established in world canon is that Andorians blue blood makes their skin blue. Of course, the real reason is that Fontana just felt like making a blue alien.

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Physiology

Still hesitant to get the shot? 7 COVID vaccine concerns addressed – CU Boulder Today

Image caption:Osvaldo Villagrana, 24, an integrativephysiology major at CUBoulder gets his first dose of the Moderna vaccine.

Nearly a third of the U.S. population is now fully vaccinated against COVID-19, and 44% have gotten shot one of a two-dose regimen. In Colorado, nearly half of eligible residents have gotten their first jab.

But vaccine efforts have begun to plateau in some areas of the country, with hesitant Coloradans including some college students expressing concerns about the pace of the vaccines development and potential side effects and uncertainty about whether benefits outweigh risks.

Teresa Foley, a teaching professor of distinction in the Department of Integrative Physiology, has heard it all in her classes.

I tell my students, This is a no judgment zone. Ask me any question you want, says Foley, who teaches immunology and epidemiology at CU Boulder. If you are not a science major or dont completely understand how the vaccine works, I can understand how you could be hesitant. Its all about education. To help inform the students, I show data about vaccine safety and efficacy and I explain how vaccines work in lay terms.

Heres a look at the most common reasons she hears for people expressing hesitancy, and what she tells them:

Teresa Foley

A lot of individuals are concerned about how quickly the vaccines were developed. They feel like it was a rushed process, as it typically takes about 73 months to develop a vaccine and this was done in 14 months. I ask them to think about it in terms of a group project. Yes, it may seem it was developed faster than usual. But never before has the entire world been working on the same group project at the same time.

Out of 326 trials and 111 vaccine candidates worldwide, only 14 have been approved by at least one country.That shows the process is working. As a scientist myself, I trust it.

Actually, when you look at the number of people enrolled in previous vaccine trials, those numbers are miniscule compared to the clinical trials for the COVID-19 vaccines. For instance, there were 8,884 participants in the clinical trial for the influenza vaccine and 5,803 for the chicken pox (Varicella) vaccine. In contrast, The Moderna trial included 30,000, Pfizer included 43,448, and Johnson & Johnson (which uses a different technology) included more than 44,000.

This is not possible with the mRNA vaccines, as the vaccine does not contain the SARS-CoV-2 virus. The vaccine only contains the instructions for how to make the spike protein on the virus so your body can recognize it and mount an immune response against it.

If someone does test positive for COVID-19 right after getting the vaccine, it may be that they were exposed to the virus before they got the shot or before they were fully protected (which is two weeks after the last dose). It was just a case of bad timing.

This is true, but exceedingly rare. These are called breakthrough cases. For instance, of 21,720 trial participants who got the Pfizer vaccine, eight got infected with COVID-19. In the placebo group, which was about the same size, 162 got infected. That brings the efficacy rate of the COVID-19 vaccine to about 95%. The efficacy of the flu vaccine, by comparison, is about 50% on a good year.

And if you were to get sick after being fully vaccinated for COVID-19, your antibodies would be built up so your symptoms would likely be mild.

Every time you get re-exposed to the same virus, your immune system builds a memory response to the virus, creating antibodies to protect you. If you get the COVID-19 vaccine after having been previously infected, your body will develop a bigger, faster and stronger antibody response to the virus. You may have some immunity against the virus if you already had COVID-19, but the vaccine will give you even more.

College students tend to think they are invincible. But they dont quite think about the idea of herd immunity, in that when we get vaccinated, we are protecting not only ourselves but also others who cant get the vaccine. The more everyone can develop immunity against the virus, the more we can protect the younger, older and immune-compromised population.

For things to return to normal, some research says at least 70% of the population must be vaccinated. If you can get the vaccine, you should.

The side effects are real but typically mild, including pain and swelling at the injection site, fever and chills and in some cases, tiredness and headache. The side effects only last a few days and mean your immune system is mounting a response and the vaccine is working. I ask students to compare this to the potential consequences of actually getting COVID-19, where symptoms can sometimes persist for monthseven in those who had a mild version of the disease.

Learn more about vaccines and how to get them.

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Still hesitant to get the shot? 7 COVID vaccine concerns addressed - CU Boulder Today

Physiology

3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study – DocWire…

Lancet Respir Med. 2021 May 5:S2213-2600(21)00174-0. doi: 10.1016/S2213-2600(21)00174-0. Online ahead of print.

ABSTRACT

BACKGROUND: The consequences of COVID-19 in those who recover from acute infection requiring hospitalisation have yet to be clearly defined. We aimed to describe the temporal trends in respiratory outcomes over 12 months in patients hospitalised for severe COVID-19 and to investigate the associated risk factors.

METHODS: In this prospective, longitudinal, cohort study, patients admitted to hospital for severe COVID-19 who did not require mechanical ventilation were prospectively followed up at 3 months, 6 months, 9 months, and 12 months after discharge from Renmin Hospital of Wuhan University, Wuhan, China. Patients with a history of hypertension; diabetes; cardiovascular disease; cancer; and chronic lung disease, including asthma or chronic obstructive pulmonary disease; or a history of smoking documented at time of hospital admission were excluded at time of electronic case-note review. Patients who required intubation and mechanical ventilation were excluded given the potential for the consequences of mechanical ventilation itself to influence the factors under investigation. During the follow-up visits, patients were interviewed and underwent physical examination, routine blood test, pulmonary function tests (ie, diffusing capacity of the lungs for carbon monoxide [DLCO]; forced expiratory flow between 25% and 75% of forced vital capacity [FVC]; functional residual capacity; FVC; FEV1; residual volume; total lung capacity; and vital capacity), chest high-resolution CT (HRCT), and 6-min walk distance test, as well as assessment using a modified Medical Research Council dyspnoea scale (mMRC).

FINDINGS: Between Feb 1, and March 31, 2020, of 135 eligible patients, 83 (61%) patients participated in this study. The median age of participants was 60 years (IQR 52-66). Temporal improvement in pulmonary physiology and exercise capacity was observed in most patients; however, persistent physiological and radiographic abnormalities remained in some patients with COVID-19 at 12 months after discharge. We found a significant reduction in DLCO over the study period, with a median of 77% of predicted (IQR 67-87) at 3 months, 76% of predicted (68-90) at 6 months, and 88% of predicted (78-101) at 12 months after discharge. At 12 months after discharge, radiological changes persisted in 20 (24%) patients. Multivariate logistic regression showed increasing odds of impaired DLCO associated with female sex (odds ratio 861 [95% CI 283-262; p=00002) and radiological abnormalities were associated with peak HRCT pneumonia scores during hospitalisation (136 [113-162]; p=00009).

INTERPRETATION: In most patients who recovered from severe COVID-19, dyspnoea scores and exercise capacity improved over time; however, in a subgroup of patients at 12 months we found evidence of persistent physiological and radiographic change. A unified pathway for the respiratory follow-up of patients with COVID-19 is required.

FUNDING: National Natural Science Foundation of China, UK Medical Research Council, and National Institute for Health Research Southampton Biomedical Research Centre.

TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

PMID:33964245 | DOI:10.1016/S2213-2600(21)00174-0

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Physiology

New grant-funded research could help improve therapies for sepsis – Newswise

Newswise A University of Kentucky College of Medicine professor has been awarded a $1.9 million National Institutes of Health (NIH) grant for his research on the bodys immune response to sepsis, which could potentially help to improve therapies for the common disease.

Xiangan Li, a professor in the Department of Physiology and the Saha Cardiovascular Research Center, received the prestigious R35 grant from the NIHs National Institute of General Medical Sciences (NIGMS), which will fund sepsis research in his lab over the next five years.

Sepsis is a life-threatening condition that occurs when an infection triggers a chain reaction throughout the body. Without timely treatment, it can quickly lead to tissue damage, organ failure and death. The Centers for Disease Control and Prevention reports that nearly 270,000 Americans die as a result of sepsis every year, and one in three patients who die in a hospital has sepsis.

Li studies how hormones called glucocorticoids regulate the bodys immune system in response to sepsis. Glucocorticoids are released by the adrenal glands and help to reduce certain aspects of immune function such as inflammation. They are often supplemented as a therapy to treat sepsis and other diseases caused by an overactive immune system. However, not all sepsis patients may benefit from additional glucocorticoids, Li says.

Thirty to 60% of sepsis patients have an impaired adrenal stress response and cannot produce enough glucocorticoids, said Li. But for the others, supplementing glucocorticoids may not be necessary or beneficial.

Research conducted in Lis lab provides a proof of concept that it could actually be harmful. Septic mice were treated with glucocorticoids and those with impaired adrenal stress responses had better outcomes, but those with normal adrenal stress responses experienced increased mortality as a result of the therapy.

Li says the findings provide an explanation for why the current glucocorticoid therapy for sepsis is controversial, as the therapy is given to patients without considering the status of adrenal insufficiency. Li proposes that before giving glucocorticoids to septic patients, a precision medicine approach should be taken to identify whether or not they have an adrenal insufficiency.

Research in Lis lab will continue to give scientists a better understanding of the role glucocorticoids play in immune function, which could ultimately lead to improved patient outcomes for sepsis.

The mechanisms behind glucocorticoids and immune regulation may be different than previously understood, Li said. The ongoing research funded by this grant will answer questions that we hope will improve the overall efficacy of sepsis therapy and save many lives.

The NIGMS aims to support basic research that increases the understanding of biological processes and lays the foundation for advances in disease diagnoses and prevention. The NIGMS R35 grant, also called the Maximizing Investigators Research Award (MIRA), increases the efficiency of NIGMS funding by providing researchers with greater stability and flexibility, thereby enhancing scientific productivity and the chances for important breakthroughs.

Research reported in this publication was supported by theNational Institute of General Medical Sciencesof the National Institutes of Healthunder Award NumberR35GM141478. The content is solely the responsibilityof the authors and does not necessarily represent the official views of the National Institutes ofHealth.

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New grant-funded research could help improve therapies for sepsis - Newswise

Physiology

Signs in the blood predict when labor will begin – Futurity: Research News

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For the first time, researchers have found a way to predict when a pregnant woman will go into labor by analyzing immune and other biological signals in a blood sample, according to a study.

The findings shed light on how labor begins, a biological process that until now has been a mystery. They also lay the groundwork for a clinical blood test that could tell women with healthy, full-term pregnancies how close they are to delivery.

Current estimates are imprecise, with anything in a five-week windowfrom three weeks before to two weeks after the due dateconsidered a normal delivery time.

If we understand whats regulating labor, we might be able to do a better job of inducing labor.

The researchers expect their findings to yield a test within the next two to three years that doctors can use to predict labor onset in healthy pregnancies. The method narrows the predicted delivery time to a two-week window, and the researchers expect it will become even more precise as the technique is refined.

We found a transition from progressing pregnancy to a pre-labor phase that happens two to four weeks before the mom goes into labor, says lead author Ina Stelzer, a postdoctoral scholar in anesthesiology, perioperative, and pain medicine at Stanford University.

Weve identified a novel way to use the maternal blood to predict when a mother will go into labor. This prediction is independent from the duration of pregnancy.

The shift from ongoing pregnancy to the pre-labor phase was detected both in women who had full-term pregnancies and in women who delivered prematurely. The change to pre-labor maternal biology is characterized by changes in levels of steroid hormones, factors that control blood vessel growth and blood coagulation, and immune regulatory signals, the study shows.

The moms body and physiology start to change about three weeks before the actual onset of labor, says coauthor Virginia Winn, associate professor of obstetrics and gynecology. Its not a single switch; theres this preparation that the body has to go through.

Currently, to estimate a womans due date, clinicians count 40 weeks from the first day of her last menstrual period, taking into account ultrasound data about the babys size.

Clinicians are good at estimating gestational age, which measures the development of the fetus. But there is a disconnect between this timing and when labor starts, because whether the baby is ready is only one factor in the onset of labor, says senior author Brice Gaudilliere, associate professor of anesthesiology, perioperative and pain medicine. The other part of the equation is the mother.

Although women deliver around 40 weeks of pregnancy on average, going into labor anywhere from 37 to 42 weeks gestational age is considered normal. More precise prediction of when the baby will arrive could be helpful, for both planning and medical reasons. For instance, being able to test whether a woman with preterm contractions is in the pre-labor phase could help doctors decide whether to administer steroids, which mature the fetuss lungs before birth.

The study followed 63 women through the last 100 days of their pregnancies. They gave blood samples for analysis two to three times before delivery. All of them went into labor spontaneously, meaning none were artificially induced.

Researchers analyzed each blood sample for 7,142 metabolic, protein, and single-cell immune features. They then plotted the data against the number of days before labor that each blood sample had been taken, ensuring that the analysis would be sensitive to signals of impending labor, as opposed to signals tied primarily to pregnancy duration or the babys growth. The researchers identified, via mathematical modeling, which features in the blood best predicted labor onset.

Fifty-eight of the women gave birth after full-term pregnancies, meaning the baby did not arrive more than three weeks before the due date, and five gave birth after spontaneous preterm labor.

As they moved into the pre-labor phase, the womens blood showed surges in steroid hormones such as progesterone and cortisol, confirming prior findings about the biology of late pregnancy. The blood also showed decreasing levels of factors that help blood-vessel formation, likely a first step toward weakening the connection between the placenta and uterus, as well as increasing levels of factors needed for blood coagulation, which help prevent blood loss after delivery. Some placental proteins surged as well.

The study also found a fine-tuning of immune responses in the shift to labor preparation. The top predictive feature in the model was a regulatory immune protein, IL-1R4, that inhibits an inflammatory molecule called IL-33, the researchers say.

We were really interested in and excited about the finding that IL-33 seems to play a role in pregnancy and impending labor, Stelzer says. Near the end of pregnancy, placental material and fetal cells reach the moms blood, potentially causing an immune response. The body needs to carefully tailor the amount of inflammation that will occur during labor, Stelzer says.

The hypothesis has been that labor is an inflammatory reaction, and yes, there are signs of that, but we also found that aspects of this inflammation are toned down before labor starts, which we think may prepare the mothers immune system for the next phase, when the baby is born and healing and immune resolution begins, Gaudilliere says. It needs to be a regulated process.

The next steps in the research are to validate the findings in more pregnant women and to narrow the number of biological markers needed to predict labor onset, Stelzer says, adding that the team has already made progress on the latter.

The findings could have other important clinical implications, Winn says. If we understand whats regulating labor, we might be able to do a better job of inducing labor, she says.

The study appears in Science Translational Medicine.

Funding came from the Doris Duke Charitable Foundation, the Burroughs Wellcome Fund, the German Research Foundation, the Stanford Maternal and Child Health Research Institute, the Prematurity Research Fund, the March of Dimes Prematurity Research Center at Stanford University, the Bill & Melinda Gates Foundation and Center for Human Systems Immunology, the Charles B. and Ann L. Johnson Research fund, the Christopher Hess Research Fund, the Providence Foundation Research Fund, the Roberts Foundation Research Fund, the Charles and Mary Robertson Foundation, the National Institutes of Health, the American Heart Association, the Stanford Maternal and Child Health Research Institute Harmon Faculty Scholar Award, the H&H Evergreen Faculty Scholar Award, and the Stanford Metabolic Health Center.

Source: Stanford University

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Signs in the blood predict when labor will begin - Futurity: Research News

Anatomy

Jesse Williams’s Heartbreaking ‘Grey’s Anatomy’ Instagram Is Absolutely Destroying Fans – GoodHousekeeping.com

The latest shocking Grey's Anatomy cast exit cuts deep.

After playing Dr. Jackson Avery on the popular medical drama for over a decade, actor Jesse Williams will be leaving Grey's Anatomy ahead of the season 17 finale this spring. According to Deadline, the last episode for Jesse's character will air on May 20.

"Jesse Williams is an extraordinary artist and activist. Watching his evolution these past 11 years both on screen and off has been a true gift," Greys Anatomy executive producer and showrunner Krista Vernoff told Deadline in a statement. "Jesse brings so much heart, such depth of care, and so much intelligence to his work. We will miss Jesse terribly and we will miss Jackson Avery played to perfection for so many years."

The fans will also surely miss seeing the Chief of Plastic Surgery every Thursday night. To announce his exit from the series, Jesse posted screenshots of the Deadline report along with a photo of himself in character to his Instagram page. His caption for the heartbreaking post simply read: "Feels ..."

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Immediately, Grey's fans flooded the comment section. "Im not accepting your resignation !! ," one fan wrote. "Cant believe youre leaving us," another said. "Crying on the floor as we speak," someone else said.

Meanwhile, several of Jesse's cast members also had things to say. "Congrats my man! What an awesome run. The water is warm out here looking forward to whats next. ," Giacomo Gianniotti, who recently left the series this year as well, wrote. "Love You. Mama is lost without you," Debbie Allen, who plays Jackson's mother Catherine on the show, said.

What's more, when the Twitter page for Grey's Anatomy tweeted out a gif of Jackson crying, Ellen Pompeo, a.k.a. Meredith Grey herself, responded, "Yeah I know the feeling @iJesseWilliams ."

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Since news about Jesse leaving broke last week, the actor hasn't provided a clear reason for departing the series. That said, the Deadline report does indicate that Jesse's latest two-year contract was coming up at the end of the current season. Jesse had first joined way back in 2009 and was promoted to a series regular following season 6.

Jesse, like his character, will be moving onto different projects. When he signed his new contract in 2019, he reportedly "scaled back duties" on Grey's after preparing to make his Broadway debut for the revival of Richard Greenbergs Take Me Out. Since the project was delayed by the pandemic, the show is expected to open in early 2022.

His IMDB page also notes that Jesse is set to act in the upcoming films Team Joy (he'll also be a producer) and Marked Man.

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Reflecting on his Grey's run, Jesse made it clear that he has enjoyed his time on the series, which tells us he is likely leaving on good terms.

"I will forever be grateful for the boundless opportunities provided me by Shonda [Rhimes], the network, studio, fellow castmates, our incredible crew, Krista, Ellen, and Debbie," Jesse said in a statement to Deadline. "As an actor, director, and person, I have been obscenely lucky to learn so much from so many, and I thank our beautiful fans, who breathe so much energy and appreciation into our shared worlds. The experience and endurance born of creating nearly 300 hours of leading global television is a gift Ill carry always. I am immensely proud of our work, our impact, and to be moving forward with so many tools, opportunities, allies, and dear friends."

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Jesse Williams's Heartbreaking 'Grey's Anatomy' Instagram Is Absolutely Destroying Fans - GoodHousekeeping.com