Several months ago, a lab technologist at Barnes-Jewish Hospital mixed the blood components of two people: Alphonso Harried, who needed a kidney, and Pat Holterman-Hommes, who hoped to give him one.

The goal was to see whether Harrieds body would instantly see Holterman-Hommes organ as a major threat and attack it before surgeons could finish a transplant. To do that, the technologist mixed in fluorescent tags that would glow if Harrieds immune defense forces would latch onto the donors cells in preparation for an attack. If, after a few hours, the machine found lots of glowing, it meant the kidney transplant would be doomed. It stayed dark: They were a match.

I was floored, said Harried.

Both recipient and donor were a little surprised. Harried is Black. Holterman-Hommes is white.

Could a white person donate a kidney to a Black person? Would race get in the way of their plans? Both families admitted those kinds of questions were flitting around in their heads, even though they know, deep down, that its more about your blood type and all of our blood is red, as Holterman-Hommes put it.

Scientists widely agree that race is a social construct, yet it is often conflated with biology, leaving the impression that a persons race governs how the body functions.

Its not just laypeople its in the medical field as well. People often conflate race with biology, said Dr. Marva Moxey-Mims, chief of pediatric nephrology at Childrens National Hospital in Washington, D.C.

Shes not talking just about kidney medicine. Race has been used as a shorthand for how peoples bodies work for years across many fields not out of malice but because it was based on what was considered the best science available at the time. The science was not immune to the racialized culture it sprung from, which is now being seen in a new light. For example, U.S. pediatricians recently ditched a calculation that assumed Black children were less likely to get a urinary tract infection after new research found the risk had to do with a childs history of fevers and past infections not race. And obstetricians removed race and ethnicity from a calculation meant to gauge a patients ability to have a vaginal birth after a previous cesarean section, once they determined it was based on flawed science. Still, researchers say those race-based guidelines are just a slice of those being used to assess patients, and are largely based on the assumption that how a person looks or identifies reflects their genetic makeup.

Race does have its place during a doctors visit, however. Medical providers who give patients culturally competent care the act of acknowledging a patients heritage, beliefs, and values during treatment often see improved patient outcomes. Culturally competent doctors understand that overt racism and microaggressions can not only cause mental distress but also that racial trauma can make a person physically sick. Race is a useful tool for identifying population-level disparities, but experts now say it is not very useful in making decisions about how to treat an individual patient.

Because using race as a medical shorthand is at best imprecise and at worst harmful, a conversation is unfolding nationally among lawmakers, scientists, and doctors who say one of the best things patients can do is ask if and how their race is factored into their care.

Doctors and researchers in kidney care have been active recently in reevaluating their use of race-based medical guidance.

History is being written right now that this is not the right thing to do and that the path forward is to use race responsibly and not to do it in the way that weve been doing in the past, says Dr. Nwamaka Eneanya, a nephrologist with Fresenius Medical Care, who in a previous position with the University of Pennsylvania traced in the journal Nature the history of how race a social construct became embedded in medicine.

The perception that there is such a thing as a Black or white kidney quietly followed patient and donor as Harried and Holterman-Hommes were on the path to the transplant in their medical records and in the screening tests recommended.

Medical records described Harried as a 47-year-old Black or African American male and Holterman-Hommes as a 58-year-old, married Caucasian female. Harried does not recall ever providing his race or speaking with his physicians about the influence of race on his care, but for two years or more his classification as Black or African American was a factor in the equations doctors used to estimate how well his kidneys were working. As previous KHN reporting lays out, that practice distinguishing between Black and non-Black bodies was the norm. In fall 2021, a national committee determined race has no place in estimating kidney function, a small but significant step in revising how race is considered.

Dr. Lisa McElroy, a surgeon who performs kidney transplants at Duke University, said the constant consideration of race is the rule, not the exception, in medicine.

Medicine or health care is a little bit like art. It reflects the culture, she said. Race is a part of our culture, and it shows up all through it and health care is no different.

McElroy no longer mentions race in her patients notes, because it really has no bearing on the clinical care plan or biology of disease.

Still, such assumptions extend throughout health care. Some primary care doctors, for example, continue to hew to an assumption that Black patients cannot handle certain kinds of blood pressure medications, even while researchers have concluded those assumptions dont make sense, distract doctors from considering factors more important than race like whether the patient has access to nutritious food and stable housing and could prevent patients from achieving better health by limiting their options.

Studying population-level patterns is important for identifying where disparities exist, but that doesnt mean peoples bodies innately function differently just as population-level disparities in pay do not indicate one gender is fundamentally more capable of hard work.

If you see group differences theyre usually driven by what we do to groups, said Dr. Keith Norris, not by innate differences in those groups. Still, medicine often continues to use race as a crude catchall, said Norris, a UCLA nephrologist, as if every Black person in America experiences the same amount and the same quantity of structural racism, individualized racism, internalized racism, and gene polymorphisms.

In Harried and Holterman-Hommes case, one striking example of race being used as shorthand for determining how peoples bodies work was an informational guide given to Holterman-Hommes that said African Americans with high blood pressure could not donate an organ, but Caucasians with high blood pressure might still qualify.

I cant believe they actually wrote that down, said Dr. Vanessa Grubbs, a nephrologist at the University of California-San Francisco. That worries Grubbs because using race as a reason to exclude donors can create a situation in which Black transplant recipients have to work harder to find a living donor than others would.

I do think that criteria such as these become barriers for transplantation, said Dr. Rajnish Mehrotra, head of nephrology at the University of Washington. He said that type of hypertension distinction could exclude potential donors like the 56% of Black adults with high blood pressure in the U.S. when more of them are sorely needed.

The inclusion of race did not necessarily affect Harrieds ability to receive a kidney, nor Holterman-Hommes ability to give him one. But following their case offers a glimpse into the ways race and biology are often cemented together.

The St. Louis Case

Harried and Holterman-Hommes met 20 years ago when they worked together at a nonprofit that serves youth experiencing homelessness in St. Louis. Harried was the guy who pulled kids out of their ruts and into a creative mindset, from which they would write poems and songs and do artwork. Holterman-Hommes said he was the calm in their storm. Harried calls Holterman-Hommes big stuff because she is the nonprofits CEO who keeps the lights on and the donations coming in. You never knew that she was the president of the company, said Harried. There wasnt an air about her.

Harried resigned in 2018 as his health declined. Then in 2021, Holterman-Hommes saw a KHN article about Harried and decided to see if she could help her former colleague. Although Holterman-Hommes mother was born with one kidney, she had lived a long and healthy life, so Holterman-Hommes figured she could spare one of her own.

As Holterman-Hommes explored becoming a donor candidate, initial tests showed high blood pressure readings, in addition to lower-than-ideal kidney function. But I like to get an A on a test, she said, so she redid both sets of tests, repeating the kidney function test after staying better hydrated and the blood pressure test after a big work deadline had passed. She moved on in the screening process after her results improved.

Grubbs wonders whether, if Holterman-Hommes had been Black, they would have just dismissed her. Grubbs shared an instance in which she suspects thats exactly what happened to the wife of a patient of hers in California who needed a kidney transplant.

The wife, who is Black and was in her 50s at the time, wasnt allowed to give the patient a kidney because of her hypertension.

There are people in this country that will tell you that, Oh, white people donate kidneys, Black people dont donate kidneys, and thats not true, said Mehrotra. You hear that racist trope. But [there are] all of these barriers to kidney donation.

Barnes-Jewish Hospital later said it had given Holterman-Hommes an outdated guide, an unfortunate circumstance that is being corrected, and provided a new one that does not say Black people with hypertension cannot donate. Instead, it says that people cannot donate if they have hypertension that was either diagnosed before age 40 or requires more than one medication to manage.

But at some point, it was a policy, said Harried, whose kidneys have been failing for several years. And its unclear how many years that outdated guidance shaped perceptions among those seeking care at Barnes-Jewish, which performs more living-donor kidney transplants per year than any other location in Missouri, according to the Scientific Registry of Transplant Recipients.

There is little transparency into how medical centers incorporate race into their decision-making and care. Guidelines from the United Network for Organ Sharing, the national organization in charge of the transplant system, leave the door open for hospitals to exclude a donor with any condition that, in the hospitals medical judgment, causes the donor to be unsuitable for organ donation.

Tanjala Purnell, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health studying disparities in kidney transplantation, said she knows of several centers that used race-based criteria, though some have relaxed those rules, instead deciding case by case. Theres not a standard set to say, Well, no, you can absolutely not have different rules for different people, she said. We dont have those safeguards. Dr. Tarek Alhamad, medical director of the kidney program at the Washington University and Barnes-Jewish Transplant Center, said race-based criteria for kidney donations arent created to exclude Black people it was born of a desire to avoid harming them.

African Americans are more likely to have end-stage renal disease, they are more likely to have end-stage renal disease related to hypertension. And they are more likely to have genetic factors that would lead to kidney dysfunction, said Alhamad.

Compared with white and Hispanic donors, non-Hispanic Black donors are known to be at higher risk for developing kidney failure because of their donation, though its still very rare.

He said it feels unethical to take a kidney from someone who may really need it down the line. This is our role as physicians not to do harm.

The Science

Researchers are studying a possible way to clarify who is really at risk in donating a kidney, by identifying specific risk factors rather than pinning odds on the vague concept of race.

Specifically, a gene called APOL1 could influence a persons likelihood of developing kidney disease. All humans have two copies of this gene, but there are different versions, or variants, of it. Having two risk variants increases the chance of kidney injury.

The risk variants are most prevalent in people with recent African ancestry, a group that crosses racial and ethnic boundaries. About 13% of African Americans have the double whammy of two risk variants, said Dr. Barry Freedman, chief of nephrology at the Wake Forest School of Medicine. Even then, he said, their fate isnt sealed most people in that group wont get kidney failure. We think they need a second hit, like HIV infection, or lupus, or covid-19.

Freedman is leading a study that looks, in part, at how kidney donors with those risk variants fare in the long term.

This is really important because the hope is that kidneys wont be discarded or turned down as frequently, said Moxey-Mims, who is also involved in the research.

Researchers who are focused on health equity say that while APOL1 testing could help separate race from genetics, it could be a double-edged sword. Purnell pointed out that if APOL1 is misused for example, if a transplant center makes a blanket rule that no one with two risk variants can donate, rather than using it as a starting point for shared decision-making, or if doctors offer the test based only on a patients looks it could merely add another criterion to the list by which certain people are excluded.

We have to do our due diligence, said Purnell, to ensure that any effort to be protective doesnt end up making the pool of available donors for certain groups smaller and smaller and smaller. Purnell, McElroy, and others steeped in transplant inequities say that as long as race which is a cultural concept defining how someone identifies, or how they are perceived is used as a stand-in for someones ancestry or genetics, the line between protecting and excluding people will remain fuzzy.

Thats the heart of the matter here, said McElroy.

So where does race belong in kidney transplant medicine? Many of the physicians interviewed for this article many of them people of color said it primarily serves as a potential indicator of hurdles patients may face, rather than as a marker of how their bodies function.

For example, McElroy said she might spend more time with Black patients building trust with them and their families, or talking about how important living donations can be, similar to the ways she might spend more time with a Spanish-speaking patient making sure they know how to access a translator, or with an elderly patient emphasizing how important physical activity is.

The purpose is not to ignore the social determinants of health of which race is one, she said. Its to try to help them overcome the race-specific or ethnicity-specific barriers to receiving excellent care.

While all the science gets sorted out, Eneanya is trying to get the message out to patients: Just ask the question: Is my race being used in my clinical care? And if it is, first of all, what race is in the chart? Is it affecting my care? And what are my options?

Just keep your eyes open, ask questions, said Harried.

In late April, a kidney from Holterman-Hommes body was successfully placed into Harrieds. Both are home now and say they are doing well.

Rae Ellen Bichell: rbichell@kff.org,@raelnb

Cara Anthony: canthony@kff.org,@CaraRAnthony

Original post:
Race Is Often Used as Medical Shorthand for How Bodies Work. Some Doctors Want to Change That. - Kaiser Health News

Recommendation and review posted by Bethany Smith

Measuring how old a persons sperm is could help predict the chances of them getting pregnant, according to a new study. But sperms age isnt just how many birthdays its had. It takes about 64 days for a sperm cell to mature, and depending on how much sex youre having (or how much youre masturbating), its released into the world shortly thereafter. But a sperms age has nothing to do with that cycle. Instead, it has to do with the aging process that occurs at the cellular level. And that biological age is linked to how long it takes a couple to conceive.

Chronological age, or how much time a person has lived, is an important factor when it comes to pregnancy especially for pregnant people, who have a finite number of egg cells. But it doesnt tell the whole story.

All your friends from high school, they're the same age, right? says J. Richard Pilsner, Ph.D., director of Molecular Genetics and Infertility at Wayne State University in Detroit, Michigan, and lead author of the study. But that number doesn't capture some of the genetic differences they have or environmental factors like smoking or exercising, which can have major impacts on the aging process, Pilsner says.

Chronological age is actually somewhat of an arcane way of thinking about aging. If we have a precise measurement of the biological age, that's going to give us more information, he says.

Thats why his team developed a novel technique to read the true biological age of sperm cells. They measured this age by reading how much DNA methylation a sperm cell has how many of a type of chemical called methyl groups are attached to the sperms DNA, which alters how its genes are expressed. The more methylation, the older the sperm. Using this method, the researchers can tell whether sperms biological age is up to nine years younger or older than its makers chronological age.

Pilsner and his team used this technique to analyze the sperm of 379 people from 16 different locations across the U.S. from 2005 to 2009, then followed the participant couples for up to 12 months or until they got pregnant. They compared the sperms biological age against the ability of the couple to get pregnant. Couples with older sperm took 17% longer to get pregnant than people with younger sperm.

17%

How much longer it took people with older sperm to get their partners pregnant compared to people with younger sperm.

A sperms biological age can match up with a persons chronological age, but it doesnt necessarily have to. A man could be 30 years old, but his sperm's epigenetic age may be 35, and that's causing a lower pregnancy probability, Pilsner says.

Lifestyle choices can advance the biological aging of sperm. For example, the study found that men who smoked had older sperm.

Pilsner will be conducting more research on what can speed up or slow down sperm aging in the coming months, but he notes that the basics of a healthy lifestyle, sleep, diet, and exercise are important for ensuring that your cells dont mature too quickly. Future research could also shed light on whether sperms age affects the babys health.

Knowing sperms true age could also help couples get pregnant faster. If a person has very old sperm, for example, they may decide to look into assisted reproductive technology sooner.

There's very little screening for male reproductive health, Pilsner says. He hopes that the new technique for determining sperms age could one day help doctors diagnose clinical infertility, given that the semen parameters currently used have been shown to be poor predictors of reproductive success. We need this new biomarker that really captures what's happening biologically within the cell, he says.

The next step? After validating these findings, Pilsners lab will run experiments on mice to see whether there could be pharmacological options for rejuvenating older sperm cells. One day, its possible that men having trouble getting their partners pregnant could turn back the clock on their sperm to increase their chances of getting pregnant.

Not subscribed to Fatherlys newsletter yet? Were not mad, just disappointed.

Originally posted here:
The "Age" Of Your Sperm Could Predict Your Chances Of Pregnancy - Fatherly

Recommendation and review posted by Bethany Smith

Calves are one of the most stubborn muscle groups. Many people find it hard to make them grow, irrespective of how hard or often they train them in the gym.

Are big calves only for improving your physique aesthetics? Not really.

A study conducted on 6,265 people found that the bigger a persons calves, the smaller their risk of stroke. Regardless of age, sex, body mass index, and other vascular risk factors, those with bigger calves had fewer fatty deposits known as plaques built up in their arteries. It means they have a lower risk for stenosis, carotid artery disease, and strokes. [1]

If you do not wear shorts to the gym as you fear ridicule because of your tiny calves, you have come to the right place. In this article, youll learn about the average calf size for men and women of different ages, how to measure your calf circumference correctly, and how to increase your calf size.

Youve probably heard of the unwritten rules you should never ask a woman her age, a man his salary, and agym bro his calf size. Okay, we just came up with the calf size part, but make no mistake, it can be even more offending than the first two questions.

Your calf size is determined by your genetics and daily activity levels, especially if youre not a gym regular. You could alter your calf circumference with calf exercises, but it requires hard work in the gym.

According to data based on a sample of 4,303 men aged 20 years and above, the Center for Disease Control and Prevention (CDC)suggests that the average male calf size is15.5 inches. [2]

On average, men between 20 and 29 had 15.5-inch calves, while men aged 30 to 39 had 15.6-inch calves. Average male calf circumference peaks at15.8 inchesfor the40 to 49 age group.

Although men undergo a gradual increase in calf size up to the age of 49, the drop in calf circumference is comparatively drastic. Per the survey, men between 50 and 59 have 15.6-inch calves. It drops down to 15.4 inches by the time they enter their 60s.

In their 70s, men, on average, have 14.9-inch calves, which further drops to 14.2 inches by the time they are in their 80s.

Related:Ronnie Coleman Hits Calf Raises for Reps: Trying My Very Best with My Feet Totally Numb

Per the same CDC research cited above (based on the sample size of 4,133 women aged 20 and above), the average female calf size is 15 inches. [2]

For women between the ages of 20 to 29, the average calf size is 14.8 inches. It increases to 15.2 inches for women between 30 and 39 before peaking at15.4 inchesfor females aged between40 and 49.

After peaking around 50, womens calf size, on average, decreases to 15.1 inches between the age of 60 and 69. The calf size drops to 14.4 inches as women enter their 70s and hits its low at 13.9 inches in their 80s.

Although men have larger calves than their counterparts of the same age, the difference isnt as big as some might have imagined. Notably, age plays an important role in determining your calf size.

Related:The 13 Best Calf Raise Machine Alternatives for Bigger, Stronger Lower Legs

There are a few different ways of measuring your calf size. Some people like to get their calves measured while seated, while others prefer doing it standing. Calf measurements taken seated are usually bigger than those recorded standing up.

Like in the case of other muscle groups like the biceps and chest, many people like to get their calves measuredafter they have a good muscle pumpfrom performing a few sets of the lower leg exercises.

Nonetheless, it does not matter if you choose to get your calves measured standing or seated, with or without a pump, or contracted or relaxed. Make sure you do it in the same position every time for consistency.

Here is how to measure your calves correctly:

Competitive bodybuilding is a game of aesthetics, symmetry, and illusions. You do not have to build your calves to a certain size to be able to win bodybuilding shows. However, you should focus on building proportions and balance.

Arnold Schwarzenegger summed it up the best when he said

When I went to train with my hero, Reg Park, he pulled out a tape measure and measured my calves and biceps. He said, Arnold, your calves are 19 inches, and your biceps are 21 inches. You might win Mr. Universe like this, but youll never go all the way. You need to build up your calves. Every step you take is a 250-pound calf raise. So to grow, you are going to have to go as heavy as possible, and youre going to need to do 10-15 sets every single day.'

If you are a bodybuilding fan, make sure your calves are as big as your biceps. If your upper arms are bigger than your lower legs, your body might appear disproportionate.

Check Out:14 Best Legs in Bodybuilding History

Building bigger calves is easier said than done. Youll have to undergo strict training, diet, and recovery regimen to put muscle mass on your lower legs. Here is an effective calf training workout you should try the next time you hit the gym:

Next Read:15 Ways To Turn Your Calves Into Full Grown Bulls

If your calves are slightly over or under (up to 0.3 inches, either way) the average size for your age and gender, your calves will still be considered normal. However, if your calves are smaller, you should follow the workout listed above to add mass to your lower legs.

For men of average height (five-foot-nine) and weight (194.7 pounds), 16-inch calves or bigger can be considered big. On the other hand, 15.5-inch or bigger calves can be considered big for women of average height (five-foot-four) and weight (170.6 pounds). [2]

Knowing the average calf size for your age and gender gives you a good idea of where you stand in terms of your lower leg gains.

If you want to add size to your calves, you should add the workout mentioned above to your training regimen and follow a high-protein diet. On the other hand, you should switch to acalorie-deficit dietand spike your cardiovascular workouts to lose a few inches off your lower legs.

View original post here:
The Average Calf Size for Men and Women Fitness Volt - Fitness Volt

Recommendation and review posted by Bethany Smith

image:Small carpenter bee on a flower. view more

Credit: York University

TORONTO, June 17, 2022 The local environment plays a pivotal role in the health and diversity of the gut microbiome of wild bees which could help detect invisible stressors and early indicators of potential threats, say York University scientists in a new study.

Piloting a new frontier of metagenomics, the researchers sequenced whole genomes of three species of carpenter bees, a type of wild bee, in North America, Asia and Australia. This analysis allowed them to gain insights into the bees gut microbiome (bacteria and fungi), diet and viral load, as well as their environmental DNA.

Unlike social bees (like honeybees and bumblebees), the researchers found solitary bees get their microbiome, which is important for health, from their environment where they forge for food, rather than inheriting it from their nest mates. Carpenter bees burrow into woody plant stalks to lay eggs rather than in hives.

This may make them better bio-indicators as they are much more sensitive to their environment, says Faculty of Science Associate Professor Sandra Rehan, corresponding author of the research, Comparative metagenomics reveals expanded insights into intra- and interspecific variation among wild bee microbiomes, published today in the journal CommunicationsBiology.

In Australia, the local populations had highly distinctive metagenomes and microbiomes; so much so that machine learning tools were able to reliably predict from which population each bee was drawn.

The research team also discovered crop pathogens in the microbiomes of carpenter bees which were previously only found in honeybees.

These pathogens are not necessarily harmful to bees, but these wild bees could potentially be vectoring diseases that might have negative effects on agriculture, says Rehan. Finding out how these pathogens are spreading in wild bees is important as bees contribute to ecological and agricultural health worldwide in addition to more than $200 billion in annual agricultural services.

Establishing a baseline of what a healthy microbiome looks like in wild bees allows scientists to compare species across continents and populations, and to figure out how diseases and harmful microbiota are being introduced and transmitted.

We can really dissect bee health in a very systematic way looking at population genetics and parasite pathogen loads, healthy microbiomes and deviations, says Rehan, whose Postdoctoral Research Associate, Wyatt Shell, led the study. The long-term goal is really to be able to use these tools to be able to also detect early signatures of stress and habitats in need of restoration or conservation. To develop it almost like a diagnostic tool for bee health.

Researchers believe they have captured the core microbiome of carpenter bees for the first time. They found beneficial bacteria in all three carpenter bee species which helped with metabolic and genetic functions. They also detected species of Lactobacillus, which is an essential beneficial bacteria group, imperative for good gut health and found across most bee lineages. Lactobacillus may protect against prevalent fungal pathogens, boost the immune system, and facilitate nutrient uptake.

However, a recently published paper in the journal Environmental DNA by Rehan and her graduate student Phuong Nguyen, Developmental microbiome of the small carpenter bee, Ceratina calcarata, which studied the microbiome in brood and adult carpenter bees in cities, found they were lacking Lactobacillus.

This raises red flags, says Rehan. We are continuing those studies to look at more nuanced urban, rural comparisons and long-term data to really understand these environmental stressors. Anytime we characterize a microbiome and see deviations from what we know to be normal, it can give us an indication of a population or species in threat.

Overall, the results show metagenomic methods could provide important insights into wild bee ecology and health going forward.

We've been piloting this research approach in a few species, but we're aiming to study dozens of wild bee species and broader comparisons are coming. These two studies are really establishing the foundation," she says. The long-term goal is really to be able to use these tools to detect early signatures of stress in wild bees and thereby identify habitats in need of restoration or preservation. We are excited to be building the tools for a new era of wild bee research and conservation.

The work was funded by NSERC Discovery Grants, Weston Family Foundation Microbiome Initiative funds, and the NSERC E.W.R. Steacie Memorial Fellowship to Rehan.

PHOTOS: Small carpenter bee - https://www.yorku.ca/news/wp-content/uploads/sites/242/2022/06/860-header-Small-carpenter-bee.jpg

Male carpenter bee (certina calcarata) - https://www.yorku.ca/news/wp-content/uploads/sites/242/2022/06/Male-ceratina-calcarata-side-copy-scaled.jpg

Carpenter bee (ceratina australensis) nest - https://www.yorku.ca/news/wp-content/uploads/sites/242/2022/06/Ceratina_australensis_nest.jpg

Carpenter bee (ceratina japonica) - https://www.yorku.ca/news/wp-content/uploads/sites/242/2022/06/Ceratina-japonica.jpg

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York Universityis a modern, multi-campus, urban university located in Toronto, Ontario. Backed by a diverse group of students, faculty, staff, alumni and partners, we bring a uniquely global perspective to help solve societal challenges, drive positive change and prepare our students for success. York's fully bilingual Glendon Campus is home to Southern Ontario's Centre of Excellence for French Language and Bilingual Postsecondary Education. Yorks campuses in Costa Rica and India offer students exceptional transnational learning opportunities and innovative programs. Together, we can make things right for our communities, our planet, and our future.

Media Contact:Sandra McLean, York University Media Relations, 416-272-6317,sandramc@yorku.ca

Communications Biology

Animals

Comparative metagenomics reveals expanded insights into intra- and interspecific variation 2 among wild bee microbiomes

17-Jun-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Clues to bee health found in their gut microbiome - EurekAlert

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When you consider how babies are made, you bump up against a basic math problem. No need for calculus here, or even the mental gymnastics of carrying the one. Its a problem of doubling.

A mother has 23 pairs of chromosomes. A father also has 23 pairs of chromosomes. When sperm meets the egg, you would expect the embryo, and thus the fetus, and thus the baby to have 46 pairs of chromosomes. And when that baby grows up, one of its eggs, filled with 46 pairs of chromosomes, might meet-cute a sperm, carrying its own 46 pairs of chromosomes, and the result would be a baby whose cells hold onto 92 pairs of chromosomes.

Given humanitys long history on this planet and its propensity to make babies, our cells would have, by now, exploded with chromosomal goo. This surplus of DNA would be unmanageable from a containment perspective, let alone what it would do to the body. We simply do not need that much DNA. When we have one extra chromosome, such as in trisomy 21, the effects are appreciable. What would happen if we had dozens upon dozens of extra chromosomes, or hundreds?

In order to figure out natures answer to this quandary, someone needed to crawl under the metaphorical bed sheets and figure out just how babies are made. That man was Oscar Hertwig, and the procreators that captured his attention were spiny globules we call sea urchins.

Hertwig was born in 1849 in Friedberg, Germany. He and his brother Richard, one year his junior, attended university together, and Oscars curiosity was later piqued by the question of just what happened when a sperm cell and an egg cell met. Two main theories were fighting it out in academic circles at the time. The first was that the sperm touched the egg and basically vibrated against it, which spurred the egg into becoming an embryo. In this scenario, sperm was a sort of alarm clock loudly buzzing and prodding the egg to wake up and fulfill its destiny.

The second hypothesis was that the sperm penetrated the egg and their raw materials mixed and became the embryo.

Hertwig saw the evidence that had been published for this second theory but was not happy with it. When he heard that his brother was leaving for the Mediterranean to work on a research project with the preeminent biologist they had both studied under, Oscar decided to join them. And he made an important observation while there: sea urchins, which can be found on the Mediterranean seashore, had transparent embryos.

With the veil of fertilization thus lifted, Hertwig was able to witness sea urchin sperm entering a sea urchin egg cell and fusing with its nucleus, which contains the chromosomes. Sperm was no alarm clock; it mixed with the egg. Once a single sperm cell had penetrated the egg, a force field called the vitelline membrane was erected by the egg to block out the remaining sperm cells.

This is now common knowledge, but what Hertwig didnt know then was exactly what was happening to the contents of the sperm and egg when they met and what strange chromosomal dance had taken place before the sperm and egg were even created. Because that would prove to be the answer to the problem of DNA doubling up all the time.

Lets start with sperm, the simpler of the two.

Inside the testis of an adolescent male, we look for a regular cell that is about to become a sperm cell. We race past the complex structures that bring this dynamic cell to life and enter its nucleus, the command center of the cell which contains the chromosomes. We focus on chromosome 1. There are two of them, joined at the hip. Lets call them Dwayne and Matthew. Matthew was inherited from the teenage boys mom (hence the M" name), while Dwayne was a gift from his dad. They are, in a manner of speaking, fraternal twins: the same age, with similar enough features, but with important differences.

Cells, which contain Dwayne and Matthew and nearly two dozen other pairs of chromosomes, divide, like a soap bubble being pinched into two. In order to make sure that the cells that result from this division both carry Dwayne and Matthew, Dwayne and Matthew need to be copied.

And so, through the magic of molecular biology, Dwayne and Matthew, joined at the hip, find themselves next to Dominic and Marc, also joined at the hip and looking like clones of Dwayne and Matthew. We have now doubled the amount of DNA inside this cell in preparation for that bubble pinch.

But before this can happen, a critical event takes place. It does not happen in any other cell of the boys body, but strictly in those that are to become sperm cells.

Matthew, originally inherited from Mom, and Dominic, a copy of Dwayne which was inherited from Dad, get together. Its not exactly love, but more akin to one of Dr. Frankensteins experiments. A part of Matthew goes to Dominic and vice versa, creating new chromosomes: Matthinic and Domew.

What happens next is simple. Dwayne and the new chromosome Matthinic move to one end of the cell, while Domew and Marc shuffle over to the other side. The cell splits into two, and these cells then each split into two, creating four sperm cells.

There is a name for this entire process of a cell swapping material between Mommys and Daddys chromosomes after it has doubled up its DNA, then twice halving its content. Its called meiosis (pronounced my-OH-sis) and it means a lessening. It takes place in cells that are meant to become sex cells, i.e. sperm and egg in humans.

Figure 1: A simplified illustration of meiosis, using the development of sperm cells as an example. 1) Each chromosome consists of two halves, one inherited from Daddy (labelled Dwayne here) and the other inherited from Mommy (labelled Matthew), and identical copies of them are made at the beginning of this process (Dominic and Marc). 2) One of the halves inherited from Mommy swaps material with one of the halves inherited from Daddy. 3) This creates new recombinant chromosomes. 4) Eventually, each one of these chromosomes finds itself in a single sperm cell. Created with BioRender.com.

Cells which contained both Dwayne and Matthew now only contain either Dwayne or a modified version of Matthew. Where once there were two chromosomes 1 in the same cell, there is now only one. The same process concurrently affects chromosomes 2 to 22 and the sex chromosomes as well. Sperm cells thus have half as much DNA as any other cell in the body.

Meiosis also takes place in females, though the process stops-and-goes over the course of many years to eventually create egg cells that also contain half as much DNA as any other cell. (To be more accurate, some cells in our body actually contain even more DNA than regular cells, for example up to half of our liver cells.)

This is why, when a sperm penetrates an egg, we do not get 46 pairs of chromosomes.

The 23 single chromosomes of the sperm are matched with the 23 single chromosomes of the egg, and this creates a new combination of 23 pairs of chromosomes in the embryo. Only Dwayne becomes part of the embryo, or Marc, or Matthinic, or Domew, or any one of a near-infinite combination of Matthew and Dominic chromosomes, or of Dwayne and Marc recombined chromosomesall depending on which sperm wins the race.

And the egg they will fertilize will contain May, or Dawn, or Darilyn, or Marlene, or any combination of Marilyn and Darlene and of May and Dawn.

And these recombinationscreating Matthinics and Darilynsare critical events because they engender genetic diversity. Without these DNA swaps, the same chromosomes would get passed down, intact, from generation to generation. Instead, a mothers and fathers genetic contributions are scrambled inside their children when the latter start making sexual cells. This diversity benefits us: it gives us a better chance to survive when our environment changes and helps reduce the chances of our children inheriting certain genetic diseases. And this perk is not just for us. Meiosis takes place in plants and animals more broadly.

One of the core principles of toxicology is that its the dose that makes the poison. In a way, it holds true in genetics. We could not withstand a growing accumulation of chromosomes from generation to generation. Meiosis is thus key in keeping the number of chromosomes constant and helping ensure diversity.

Take-home message:- Without a special process in place, every child would receive all of its mothers and fathers DNA and thus end up with twice as much DNA as each parent- What actually happens is that sperm cells and egg cells wind up with half of the DNA of regular cells through a process called meiosis- During meiosis, equivalent chromosomes inherited from different parents swap parts of each other, which contributes to genetic diversity

@CrackedScience

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How Nature Solved the Problem of Too Much DNA - Office for Science and Society

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Compared with doctors choice of chemotherapy, Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) improved both progression-free survival and overall survival in people diagnosed with previously treated metastatic HER2-low breast cancer, according to a study.

The research was presented on June 5, 2022, at the American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in The New England Journal of Medicine. Read the abstract of Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer.

Progression-free survival is how long a person lives without the cancer growing. Overall survival is how long a person lives, whether or not the cancer grows.

Metastatic breast cancer is breast cancer that has spread to parts of the body away from the breast, such as the bones, liver, or brain.

Some breast cancer cells make, or overexpress, too many copies of the HER2 gene. The HER2 gene makes a protein known as a HER2 receptor. HER2 receptors are like ears, or antennae, on the surface of cells. These HER2 receptors receive signals that stimulate the cell to grow and multiply. But breast cancer cells with too many HER2 receptors can pick up too many growth signals and start growing and multiplying too much and too fast. Breast cancer cells that overexpress the HER2 gene are called HER2-positive.

Doctors use several tests to find out if a breast cancer is HER2-positive. Two of the most common are:

IHC (ImmunoHistoChemistry): The IHC test uses a chemical dye to stain the HER2 proteins. The IHC measures the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample and gives it a score of 0 to 3+. If the score is 0 to 1+, its considered HER2-negative. If the score is 2+, its considered borderline. A score of 3+ is considered HER2-positive.

FISH (Fluorescence In Situ Hybridization): The FISH test uses special labels that attach to the HER2 proteins. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 proteins. With the FISH test, you get a score of either positive or negative (some hospitals call a negative test result zero).

About 15% to 20% of breast cancers are HER2-positive. Still, research shows that more than 60% of breast cancers considered HER2-negative have some HER2 proteins on the surface of its cells. There just arent enough HER2 proteins for the cancer to be considered HER2-positive. Doctors now call these cancers HER2-low.

There are medicines called targeted therapies that specifically target the HER2 receptors on HER2-positive breast cancer cells. Herceptin (chemical name: trastuzumab) was the first anti-HER2 medicine developed. Still, these anti-HER2 medicines have not been effective against HER2-low breast cancers.

HER2-low breast cancer is commonly treated as if it were HER2-negative breast cancer, almost always with chemotherapy.

Enhertu is approved by the U.S. Food and Drug Administration (FDA) to treat unresectable or metastatic HER2-positive breast cancer in people who have previously received an anti-HER2 medicine:

for metastatic disease

before or after surgery for early-stage disease that came back (recurred) within six months of completing treatment

Unresectable means the cancer cant be removed with surgery.

Enhertu is a targeted therapy made up of three parts:

fam-trastuzumab: an anti-HER2 medicine that has the same basic structure as Herceptin

a topoisomerase I inhibitor chemotherapy called DXd: topoisomerase I inhibitors work by interfering with a cancer cells ability to replicate

a compound that links the fam-trastuzumab molecule to the topoisomerase I inhibitor chemotherapy molecule

Doctors call Enhertu an antibody-drug conjugate targeted therapy. The combination of the topoisomerase I inhibitor and the linking compound is called deruxtecan. The linking compound attaches (conjugates) the fam-trastuzumab to the topoisomerase I inhibitor chemotherapy.

Enhertu was designed to deliver the topoisomerase I inhibitor to cancer cells in a targeted way by attaching the topoisomerase I inhibitor to the fam-trastuzumab. The fam-trastuzumab part of Enhertu attaches to the HER2 protein, stopping it from receiving growth signals and also carries the topoisomerase I inhibitor to the cancer.

Because Enhertu contains both an anti-HER2 medicine and a chemotherapy medicine, the researchers for this study thought it might effectively treat HER2-low breast cancers.

Called DESTINY-Breast04, the study included 557 people 555 women and two men diagnosed with metastatic HER2-low breast cancer. The people joined the study between December 2018 and December 2021. All the people in the study had already received one or two lines of chemotherapy for metastatic disease.

In this study, the researchers defined breast cancer as HER2-low if it got an IHC score of 1+ or an IHC score of 2+ and a negative FISH test.

About 89% of the cancers in the study were hormone receptor-positive and about 11% were hormone receptor-negative.

About 45% of the people in the study lived in Europe or Israel and almost half were white.

The researchers randomly assigned the people to one of two treatment groups:

373 people received Enhertu; 331 (88.7%) of these people had hormone receptor-positive disease

184 people received their doctors choice of chemotherapy; 163 (88.6%) of these people had hormone receptor-positive disease

Among people who received their doctors choice of chemotherapy medicines:

51.1% received Halaven (chemical name: eribulin)

20.1% received Xeloda (chemical name: capecitabine)

10.3% received Abraxane (chemical name: albumin-bound or nab-paclitaxel)

10.3% received Gemzar (chemical name: gemcitabine)

8.2% received Taxol (chemical name: paclitaxel)

About 63% of people who received Enhertu and 61% of people who received their doctors choice of chemotherapy had previously received three or more types of treatment for metastatic disease.

The researchers followed about half the people for more than 18.4 months and half for less time.

As of Jan. 11, 2022, progression-free survival time was:

9.9 months for people who received Enhertu

5.1 months for people who received their doctors choice of chemotherapy

Overall survival time was:

23.4 months for people who received Enhertu

16.8 months for people who received their doctors choice of chemotherapy

The researchers also looked at specific subgroups of people in the study.

For people diagnosed with hormone receptor-positive disease:

progression-free survival was 10.1 months for people who received Enhertu and 5.4 months for people who received their doctors choice of chemotherapy

overall survival was 23.9 months for people who received Enhertu and 17.5 months for people who received their doctors choice of chemotherapy

For people diagnosed with hormone receptor-negative disease:

progression-free survival was 8.5 months for people who received Enhertu and 2.9 months for people who received their doctors choice of chemotherapy

overall survival was 18.2 months for people who received Enhertu and 8.3 months for people who received their doctors choice of chemotherapy

The researchers analyzed side effects in 371 people who received Enhertu and 172 people who received their doctors choice of chemotherapy.

More than 99% of the people who received Enhertu and more than 98% of people who received their doctors choice of chemotherapy had at least one side effect. About a quarter of the people in each treatment group had a serious side effect.

About 16% of people who received Enhertu and about 8% of people who received their doctors choice of chemotherapy stopped the medicine because of side effects.

The most common side effects of any grade among people receiving Enhertu were:

nausea, experienced by 73% of the people

fatigue, experienced by 47.7% of the people

hair loss, experienced by 37.7% of the people

The most common grade 3 or higher side effects among people receiving Enhertu were:

low white blood cell count, experienced by 13.7% of the people

low red blood cell count, experienced by 8.1% of the people

fatigue, experienced by 7.5% of the people

Interstitial lung disease, a general term for disorders that cause inflammation and scarring in the lungs, is a less common but serious side effect of Enhertu. Overall, 45 people who received Enhertu and one person who received the doctors choice of chemotherapy developed interstitial lung disease.

In the person who received the doctors choice of chemotherapy, the interstitial lung disease was grade 1.

Among the people who received Enhertu:

13 people had grade 1 interstitial lung disease

24 people had grade 2 interstitial lung disease

5 people had grade 3 interstitial lung disease

3 people had grade 5 interstitial lung disease

Overall, 14 people who received Enhertu and five people who received their doctors choice of chemotherapy died from drug-related causes during the study.

With these results, we have expanded the benefits of HER2 targeted therapy to a new population of breast cancer patients, said lead author Shanu Modi, MD, breast medical oncologist at Memorial Sloan Kettering Cancer Center when presenting the research. And [we] have established trastuzumab deruxtecan as the new standard of care for patients with HER2-low metastatic breast cancer. These findings have the potential to impact survival for approximately 50% of all patients diagnosed with metastatic breast cancer today.

If youve been diagnosed with metastatic breast cancer, the results of this study are extremely exciting and promising.

The attendees at the 2022 ASCO Annual Meeting were also excited. At the end of her presentation, Dr. Modi received a 40-second standing ovation.

The results of DESTINY-Breast04 are practice-changing, Dr. Modi said in an interview after her presentation. I think the strong efficacy of trastuzumab deruxtecan in this HER2-low patient population supports the need to now reclassify HER2-low as a new therapeutically targetable category of metastatic breast cancer.

Based on the results of the DESTINY-Breast04 study, you may want to talk to your doctor about the HER2 test results in your pathology report. If the score was 1+ on an IHC test or the score was 2+ on an IHC test plus a negative FISH test, Enhertu may be an option for you.

Learn more about Enhertu.

Written by: Jamie DePolo, senior editor

The rest is here:
A New Standard of Care? Enhertu Improves Survival in People With Metastatic HER2-Low Breast Cancer - Breastcancer.org

Recommendation and review posted by Bethany Smith

An experimental therapy has given one pancreatic cancer patient hope for new life.

Thanks to a one-and-done treatment, the 71-year-old womans metastatic cancer was reduced by 50% in just one month, according to her doctors. After six month, her tumors has shrunk by nearly three-quarters.

A case study about her remarkable cancer journey was published on Thursday in the New England Journal of Medicine.

Kathy Wilkes, of Ormond Beach, Florida, was diagnosed with aggressive pancreatic cancer in 2018. She underwent eight rounds of chemotherapy and an operation to remove part of her pancreas, but her cancer continued to spread into her lungs within a year.

Pancreatic cancer is one of the deadliest forms of the disease, with only about11% of patients expected to survive five years after diagnosis, according to the American Cancer Society.

Desperate to find a cure, Wilkes began looking into new treatments when she came across a 2016 case study in a prestigious research journal, also published in theNEJM, that seemed promising.

The research was undertaken by a team of more than a dozens experts, including from the National Institutes of Health following a treatment that had already helped one 50-year-old woman with colon cancer become disease-free.

Wilkes discovered that her cancer had the same KRAS G12D mutation that was investigated in the study and didnt hesitate to contact the studys lead doctor, Eric Tran, now at the Providence Cancer Institute in Portland, Oregon.

When I talked to my hometown oncologist and asked him what to do, he only had one answer, and that was chemotherapy. And I said, Thats not my answer, Wilkes told NBC News in a report published Wednesday.

After discussing with the doctors, Wilkes was also offered the highlighted gene-editing treatment, which modifies her DNA so that it will produce immune cells that recognize and attack tumor cells. Only about 4% of pancreatic cancer patients have the mutation that responds to this treatment, though the same mutation has also been found in other cancers.

Within one month of the experimental therapy, Wilkes tumors had shrunk in half. After six months, the tumors had been reduced by 72%. And while shes not yet cancer-free, her cancer has not grown since she began treatment.

I thought, That is the trial I want. I knew that that was the trial that was going to save me, save my life. I just had that feeling, Wilkes said.

The Providence Cancer Institutes Dr. Rom Leidner, co-author of the new report on Wilkes cancer treatment, called it a one-and-done measure, in NBC News report, that modified her cancer-fighting immune cells to grow and multiply over time.

Wilkes response has been encouraging, but more research is needed. Another patient with pancreatic cancer who received the same treatment at the Providence Cancer Institute did not survive.

It was an encouraging result, but its certainly far from a cure, Dr. Eric Rubin, the New England Journal of Medicines editor-in-chief, said in a statement to NBC News.

Doctors are now recruiting patients for aPhase 1 clinical trialto continue the research.

See original here:
Deadly cancer quickly shrinks by 50% with 'one-and-done' therapy: study - New York Post

Recommendation and review posted by Bethany Smith

It was a small trial, just 18 rectal cancer patients, every one of whom took the same drug.

But the results were astonishing. The cancer vanished in every single patient, undetectable by physical exam, endoscopy, PET scans or M.R.I. scans.

Dr. Luis A. Diaz Jr. of Memorial Sloan Kettering Cancer Center, an author of a paper published Sunday in the New England Journal of Medicine describing the results, which were sponsored by the drug company GlaxoSmithKline, said he knew of no other study in which a treatment completely obliterated a cancer in every patient.

I believe this is the first time this has happened in the history of cancer, Dr. Diaz said.

Dr. Alan P. Venook, a colorectal cancer specialist at the University of California, San Francisco, who was not involved with the study, said he also thought this was a first.

A complete remission in every single patient is unheard-of, he said.

These rectal cancer patients had faced grueling treatments chemotherapy, radiation and, most likely, life-altering surgery that could result in bowel, urinary and sexual dysfunction. Some would need colostomy bags.

They entered the study thinking that, when it was over, they would have to undergo those procedures because no one really expected their tumors to disappear.

But they got a surprise: No further treatment was necessary.

There were a lot of happy tears, said Dr. Andrea Cercek, an oncologist at Memorial Sloan Kettering Cancer Center and a co-author of the paper, which was presented Sunday at the annual meeting of the American Society of Clinical Oncology.

Another surprise, Dr. Venook added, was that none of the patients had clinically significant complications.

On average, one in five patients have some sort of adverse reaction to drugs like the one the patients took, dostarlimab, known as checkpoint inhibitors. The medication was given every three weeks for six months and cost about $11,000 per dose. It unmasks cancer cells, allowing the immune system to identify and destroy them.

While most adverse reactions are easily managed, as many as 3 percent to 5 percent of patients who take checkpoint inhibitors have more severe complications that, in some cases, result in muscle weakness and difficulty swallowing and chewing.

The absence of significant side effects, Dr. Venook said, means either they did not treat enough patients or, somehow, these cancers are just plain different.

In an editorial accompanying the paper, Dr. Hanna K. Sanoff of the University of North Carolinas Lineberger Comprehensive Cancer Center, who was not involved in the study, called it small but compelling. She added, though, that it is not clear if the patients are cured.

Very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure, Dr. Sanoff said in the editorial.

Dr. Kimmie Ng, a colorectal cancer expert at Harvard Medical School, said that while the results were remarkable and unprecedented, they would need to be replicated.

The inspiration for the rectal cancer study came from a clinical trial Dr. Diaz led in 2017 that Merck, the drugmaker, funded. It involved 86 people with metastatic cancer that originated in various parts of their bodies. But the cancers all shared a gene mutation that prevented cells from repairing damage to DNA. These mutations occur in 4 percent of all cancer patients.

Patients in that trial took a Merck checkpoint inhibitor, pembrolizumab, for up to two years. Tumors shrank or stabilized in about one-third to one-half of the patients, and they lived longer. Tumors vanished in 10 percent of the trials participants.

That led Dr. Cercek and Dr. Diaz to ask: What would happen if the drug were used much earlier in the course of disease, before the cancer had a chance to spread?

They settled on a study of patients with locally advanced rectal cancer tumors that had spread in the rectum and sometimes to the lymph nodes but not to other organs. Dr. Cercek had noticed that chemotherapy was not helping a portion of patients who had the same mutations that affected the patients in the 2017 trial. Instead of shrinking during treatment, their rectal tumors grew.

Perhaps, Dr. Cercek and Dr. Diaz reasoned, immunotherapy with a checkpoint inhibitor would allow such patients to avoid chemotherapy, radiation and surgery.

Progress in the field. In recent years, advancementsin researchhave changed theway cancer is treated. Here are some recent updates:

The effect of weight loss. A new study found that people who lost significant amounts of weight through bariatric surgery had a 32 percent lower risk of developing cancerand a 48 percent lower risk of dying from cancer, compared with people who did not have the surgery. According to the study, the more weight people lost, the more their cancer risk fell.

Rectal cancer. A small trial that saw 18 rectal cancer patients taking the same drug, dostarlimab, appears to have produced an astonishing result: The cancer vanished in every single participant, undetectable by physical exam, endoscopy, PET scans or M.R.I. scans. Experts believe it to be the first time in history that a study has led to complete remission in every single cancer patient.

Pancreatic cancer. Researchers managed to tame advanced pancreatic cancer in a womanby genetically reprogramming her T cells, a type of white blood cell of the immune system, so they can recognize and kill cancer cells. Another patient who received the same treatment did not survive.

Chemotherapy. A quietrevolution isunderway in the field of cancer treatment: A growing number of patients, especially those with breast and lung cancers, are being spared the dreaded treatmentin favor of other options.

Leukemia. After receiving a new treatment, called CAR T cell therapy, more than a decade ago, two patients with chronic lymphocytic leukemia saw the blood cancer vanish. Their cases offer hope for those with the disease, and create some new mysteries.

Dr. Diaz began asking companies that made checkpoint inhibitors if they would sponsor a small trial. They turned him down, saying the trial was too risky. He and Dr. Cercek wanted to give the drug to patients who could be cured with standard treatments. What the researchers were proposing might end up allowing the cancers to grow beyond the point where they could be cured.

It is very hard to alter the standard of care, Dr. Diaz said. The whole standard-of-care machinery wants to do the surgery.

Finally, a small biotechnology firm, Tesaro, agreed to sponsor the study. Tesaro was bought by GlaxoSmithKline, and Dr. Diaz said he had to remind the larger company that they were doing the study company executives had all but forgotten about the small trial.

Their first patient was Sascha Roth, then 38. She first noticed some rectal bleeding in 2019 but otherwise felt fine she is a runner and helps manage a family furniture store in Bethesda, Md.

During a sigmoidoscopy, she recalled, her gastroenterologist said, Oh no. I was not expecting this!

The next day, the doctor called Ms. Roth. He had had the tumor biopsied. Its definitely cancer, he told her.

I completely melted down, she said.

Soon, she was scheduled to start chemotherapy at Georgetown University, but a friend had insisted she first see Dr. Philip Paty at Memorial Sloan Kettering. Dr. Paty told her he was almost certain her cancer included the mutation that made it unlikely to respond well to chemotherapy. It turned out, though, that Ms. Roth was eligible to enter the clinical trial. If she had started chemotherapy, she would not have been.

Not expecting a complete response to dostarlimab, Ms. Roth had planned to move to New York for radiation, chemotherapy and possibly surgery after the trial ended. To preserve her fertility after the expected radiation treatment, she had her ovaries removed and put back under her ribs.

After the trial, Dr. Cercek gave her the news.

We looked at your scans, she said. There is absolutely no cancer. She did not need any further treatment.

I told my family, Ms. Roth said. They didnt believe me.

But two years later, she still does not have a trace of cancer.

See the rest here:
Small Study on Rectal Cancer Results in Remission in Every Patient - The New York Times

Recommendation and review posted by Bethany Smith

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People and economies globally rely substantially on the healthcare business. It is one of the fastest-growing industries. There is a correlation between income levels and healthcare spending in different nations, with healthcare spending accounting for more than 10% of most industrialized countries GDP.

The Centers for Medicare and Medicaid Services data calculates that the U.S. national healthcare expenditure reached US$ 4.1 trillion in 2020 and is forecast to surpass US$ 6.2 trillion by 2028. According to the Commonwealth Fund, the U.S. spent nearly 17% of gross domestic product (GDP) on healthcare in 2018. Switzerland was the second-highest-ranking country, spending 12.2%. In addition, New Zealand and Australia dedicate only 9.3%.

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Global COVID-19 cases have climbed above 516 million as of May 2022, and the death toll has exceeded 6.25 million. COVID-19 has disproportionately impacted specific racial and ethnic minority groups, as well as underserved and marginalized communities, highlighting the persistent challenges of health equity and health outcomes.

COVID-19 is causing a great deal of emotional, physical, and professional stress among health care personnel. The changing attitudes and behaviors of consumers, the integration of life sciences and health care, fast-growing digital health technology, new talent, and care delivery models, and clinical innovation advanced by COVID-19.

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As sector players and the customers, they serve to adapt to a new world of remote working, virtual doctor visits, and a supply chain plagued by shortages of medical goods, employees, and services, the sector is reforming to become more customer-centric.

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Gene Therapy Market Share 2022 | Product Types and Application, Growth, Share, Top Key Players with Sales, Price, Business Overview - Digital Journal

Recommendation and review posted by Bethany Smith

Almost a third of melanomas picked up during routine skin checks may not be harmful, a study suggests.

Researchers followed tens of thousands of Queenslanders over seven years and found melanoma detections were significantly higher among the group who had their skin examined by a doctor before enrolment in the study.

QIMR Berghofer Medical Research Institute cancer scientist David Whiteman, who led the study, said the results suggested that up to 29 per cent of the melanomas detected during skin checks may never have come to light if that person had not been screened.

"It suggests that skin examinations and biopsies are picking up things that look and feel just like melanomas, but they don't always behave like them or cause harm," he said.

"Under the microscope, they look like a melanoma, on the skin they look like a melanoma. But for some reason, a proportion of them will just be there on your skin and never actually burrow deeper and never spread further."

Melanoma kills about 1,400 Australians every year, with more men dying than women.

Queensland has the highest rates of the skin cancer in the world.

Professor Whiteman said the research did not lessen the importance of Australians being sun safe and undergoing regular screening for skin cancers.

But it paved the way for some "exciting" research possibilities to improve the diagnosis and treatment of the disease.

"At this point in time, we can't tell which are the bad ones and which are the good ones," ProfessorWhiteman said.

"It might be an immune thing, it might be a genetic thing, it might be a molecular thing that as yet we can't detect that makes it less aggressive and more benign."

QIMR Berghofer genetic researchers are already investigating whether particular genes in melanoma cells influence the behaviour of the skin cancer, leading to the development of more serious disease.

"We want to be able to do a test to see whether or not certain melanomas themselves carry a mutation that makes their melanomas either more or less aggressive," ProfessorWhiteman said.

He said some people may also have inherited genes that made them less vulnerable to the effects of cancers.

"Those people might have a genetic susceptibility or a genetic strength, if you like, that increases or decreases the risk of a melanoma spreading in their body," he said.

Another possibility relates to the immune system differences.

"We do know that our immune systems do mount an immune response to cancers, particularly to melanomas," Professor Whiteman explained.

"Because melanomas are often highly mutated tumours, they often express lots of weird proteins on their surface, and those proteins can provoke an immune response.

"We know that the immune system is really important in fighting melanomas but whether or not that explains why some melanomas just sit there on the skin and don't progress we don't yet know."

The big hope is that more research will lead to the identification of triggers that switch a melanoma from being benign into an aggressive tumour.

"That trigger might be something that can be targeted with a designed drug or a designed genetic therapy that might be able to switch a gene on or off," ProfessorWhiteman said.

He said further studies may also lead to better diagnostic tools.

"Patients diagnosed with melanoma have to live with the fact they have a potentially fatal cancer and endure ongoing check-ups and scans," he said.

"If we can find a way to distinguish the melanomas with a good prognosis from the very nasty melanomas, we might be able to offer patients better information about their condition and more appropriate treatment options.

"It would also help alleviate pressure on the healthcare system as melanoma treatment is very, very costly."

Professor Whiteman urged Queenslanders to continue to "slip, slop, slap" even in winter.

"Every time you get exposed to the sun, there is the potential that damage can happen," he said.

"We still advocate that you're better off never getting a melanoma in the first place.

"Primary prevention remains our strong message but early detection also is extremely important."

Cancer Council Australia recommends that people regularly examine their skin and consult their doctor if they notice any changes such as a new spot or changes in the size, shape or colour of an existing spot.

Posted6 Jun 20226 Jun 2022Mon 6 Jun 2022 at 4:15am, updated6 Jun 20226 Jun 2022Mon 6 Jun 2022 at 6:02am

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New research finds nearly a third of melanomas found during skin checks may not be harmful, improving treatment options - ABC News

Recommendation and review posted by Bethany Smith

TAMPA, Fla., June 7, 2022 /PRNewswire/ -- Pinnacle Fertility (Pinnacle), the fastest-growing network of physician-centered fertility practices representing more than seven clinics and 20 locations nationwide, has partnered with Igenomix as their exclusive preimplantation genetics testing (PGT) laboratory and provider for genetic counseling services. Continuing Pinnacle's commitment to collaborative medical leadership and patient-first care, this strategic partnership was the result of the Medical Council's collective determination and offers patients an increased opportunity to find success in their family-building journey.

"Our Medical Director Council extensively studied the science behind major genetic labs to determine which would provide us with the best possible data to make key decisions. Bringing Igenomix on as our exclusive genetics provider for Pinnacle Fertility clinics continues to ensure that we meet our single guiding principle which is to provide the best patient outcomes possible," shares Dr. Richard Marrs, Chief Medical Director for Pinnacle Fertility.

With more than 15 years of experience, Igenomix is the global leader in reproductive genetics and focuses on quality, safety, and science to help healthcare professionals and patients detect genetic abnormalities before treatment, avoid implantation failure, and ensure patients achieve a healthy pregnancy.

"Pinnacle Fertility continues to set the standard in fertility care by bringing leading technology, integration and innovation to its suite of family building services. Partnerships with companies like Igenomix, who are committed though-leaders like we are, benefit our patients and those seeking to grow their families with the help world-class reproductive genetic testing and counseling services," says Andrew Mintz, CEO at Pinnacle Fertility.

PGT is an elective treatment option that can be used to identify embryos at risk of having a specific genetic or chromosomal condition and is available for patients at all fertility clinics within the Pinnacle network. Igenomix offers the most comprehensive portfolio of infertility treatments for genetics and was the first organization to launch non-invasive PGT-A services. Patients who choose to use PGT as part of their treatment plan receive complementary pre- and post-test genetic counseling to help guide and educate them on their options and results.

"Bringing Igenomix onboard is an exciting opportunity for our patients to seamlessly have access to genetic testing and counseling services, such as PGT at our fertility clinics," shares Dr. Dr. Priya Maseelallfrom Reproductive Gynecology and Infertility "The genetic counselors are perfectly integrated into our programs and champion our patients' success like we do."

Patients electing to use PGT, undergo in vitro fertilization (IVF) to create embryos, and then cells are removed from each embryo for genetic testing. Embryos with normal results are selected to be transferred into the uterus in hopes of achieving a pregnancy and delivering a child without a genetic condition. By utilizing PGT, genetic diseases can be prevented. In addition, studies have shown that PGT can not only improve success rates but also provide optimism and peace of mind during pregnancy and after birth.

About Pinnacle Fertility

Pinnacle Fertility is the nation's fastest-growing physician-centric fertility care platform, supporting high-performing fertility clinics and comprehensive fertility service providers nationwide. Under a united mission of fulfilling dreams by building families, Pinnacle clinics offer innovative technology and processes, compassionate patient care, and comprehensive fertility treatment services, ensuring families receive a high-touch experience on their path to parenthood.

For more information about Pinnacle Fertility, visit pinnaclefertility.com

About Igenomix

Igenomix is a global leader in reproductive genetic testing with laboratories in 23 countries and assisting hundreds of thousands of patients per year worldwide. As part of Vitrolife Group, the company is recognized for its R&D expertise and quality of service. In the US, Igenomix has proven to be the best-in-class when comes to credibility, consistency on their results, automatization of their laboratories and the most important, patient care.

Learn more about Igenomix at Igenomix.com

Contact:Walt Conrad[emailprotected]

SOURCE Pinnacle Fertility

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PINNACLE FERTILITY PARTNERS WITH IGENOMIX AS THEIR EXCLUSIVE GENETICS LABORATORY AND GENETIC COUNSELING PROVIDER - PR Newswire

Recommendation and review posted by Bethany Smith

Abbott Nutrition has resumed formula production in its Michigan plant to address the nationwide formula shortage; 2 distinct strains of monkeypox may indicate rapid, undetected spread nationwide; the overturn of Roe v Wade could have an effect on in vitro fertilization and genetic testing.

Abbott Nutrition resumed production of baby formula on Saturday in order to address the nationwide shortage after getting the green light from the FDA. Production of EleCare and other specialty and metabolic formulas will be the first to restart production, with a product release of June 20 as the target date, according to CNBC. Abbott Nutrition was initially closed in February due to contamination. The FDA has said in a statement that it is working diligently to ensure safe resumption of infant formula production. The FDA also said that it hopes that this measure will put more baby formula on the shelves nationwide.

A recent genetic analysis of monkeypox cases indicated that there are 2 distinct strains in the United States, which could mean that the virus has been circulating in the country for some time, according to AP News. There are many monkeypox cases with the same strain as the recent cases in Europe; however, the recent analysis showed a different strain as well and both strains were in the United States last year. More analysis will need to be done to determine how long monkeypox has been in the United States. These findings could mean that the virus will be difficult to contain in the future.

The overturning of Roe v Wade could have effects on reproductive medicine at large as state policies could determine how birth control is provided or in vitro fertilization (IVF), according to STAT News. In the states that are expected to ban or limit abortion, lab-made embryos would also have legal protections, which could make IVF more complicated. Preimplantation genetic testing could also come under scrutiny as embryos that arent implanted may not be able to be frozen if they are considered people with legal rights. Alabamas anti-abortion law only applies to embryos in the womb, which would allow IVF; however, experts are still figuring out whether Oklahomas anti-abortion law will also extend to IVF.

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What We're Reading: Abbott to Resume Formula Production; 2 Strains of Monkeypox; Impact of SCOTUS Decision on IVF, Embryo Genetic Testing - AJMC.com...

Recommendation and review posted by Bethany Smith

From left, Farah Khan, Tracy Ismail, Sophia Ahmed, Amara Ismail and Durrah Khan

Three siblings have already had their stomachs removed after testing positive for a faulty cancer gene following the deaths of their mother and sister from the disease.

Now further members of the family have been found to carry the faulty gene, with several children, who are too young to be tested, under threat of inheriting it.

Walsall siblings Sophia Ahmed, 42, Tahir Khan, 48, and Omar Khan,31 underwent the surgery after a series of tests at Addenbrooke's Hospital in Cambridge.

The family joined Cancer Research UKs Familial Gastric Cancer study after losing their mum and sister to hereditary stomach cancer.

Determined to give back to the charity that has given them hope, Sophia, who has recently had her breasts removed as well as her stomach, is joining with four other female relatives to help launch Cancer Research UKs Race for Life Pretty Muddy events across the region.

Sophia and her two brothers took their radical decision to have their stomachs removed after genetic testing showed they had the CDH1 gene and were at high risk of the same cancer that killed their mother, Pearl Khan, in 2002 at the age of 49, and their sister, Yasmin Khan, in 2012 at the age of 32.

The family team named Little Hooligans Get Dirty for Cancer - is being led by Amara Ismail, 32, manager of the Little Hooligans soft play centre in Walsall, and her mum Tracy Ismail, 51, the only one of the five siblings unaffected by the gene. Joining Amara is her cousin, Farah Khan, 23, whose father Tahir had preventive surgery to remove his stomach.

Youngest of the team is 14-year-old Durrah Khan, whose mum, Yasmin Khan, passed away from stomach cancer in 2012. It was Yasmins death that spurred the rest of the family to find out about research being done in the area, and led to them joining the Familial Gastric Cancer study.

Farah has also tested positive for the faulty gene and is taking part in the same Cancer Research UK research study as her father. She is regularly monitored at Addenbrookes hospital in Cambridge and may also be offered the opportunity to have preventative surgery.

Sophia said: Having your stomach removed is a fairly drastic thing to do, but after I had the surgery they told me that the cancer had already started in my stomach and I would have been dead within a year if it hadnt been removed. I was at very high risk of breast cancer too, so a double mastectomy was the best way to prevent it.

Research is so important. Its thanks to research that Im alive, and that other members of my family are still here too. I truly believe that more research could lead to the complete eradication of this genetic form of cancer.

The team has signed up for Pretty Muddy Sandwell - a mud-splattered obstacle course that raises money for life-saving research - which takes place at Sandwell Valley Country Park on Saturday, June 25. There is also the chance for boys and girls aged five to 12 to take part in Pretty Muddy Kids - their own version of the fun event.

Amara said: Cancer research UK is a very close charity to me and my family. My aunt Yasmin was the same age as I am now when she passed away. My surviving auntie and two uncles have all had preventative surgery at Addenbrookes hospital with the help of Cancer Research UK. Their very high risk of cancer was discovered after they had genetic testing which showed they had the CDH1 gene.

I am very fortunate in that my mum was the only one of five siblings not to have the faulty gene, so it hasnt been passed onto me either. But the impact on my wider family has been huge and has affected every generation.

My cousin's genetic tested showed she also had the faulty gene and she is now waiting to find out how it is going to affect her life. We have a further six children, including Durrah who is part of the Pretty Muddy team, who are yet to reach the age where they can be tested.

Were so grateful for this research study that is helping all of us stay healthy and avoid cancer. But also, as a family we're invested in helping our future generations.

Farah, who inherited the genetic fault from her father, Tahir, is regularly screened for the disease. She said: Its good to know that screening will pick up early signs of any problems and that, like my dad, I can take steps to prevent cancer in the future.

Jane Redman,Cancer Research UKs spokesperson in the West Midlands, said: We are incredibly grateful to all the wonderful ladies from this special family their support. Their story speaks volumes about how important research is and why we need to keep funding it.

Our Race for Life eventsareopen to all. For some people, the Race for Life is literally a walk in the park. For others, its a jog. Some may opt to push themselves harder, taking up the challenge of Pretty Muddy or even pushing for a new personal best time.

Were looking forward to welcoming people of all ages and abilities. Race for LifePretty Muddy in Sandwellwill be a fun, emotional, colourful, uplifting and unforgettable event this year.

To enter, visitraceforlife.org. To sponsor the team, go to fundraise.cancerresearchuk.org/team/little-hooligans-gets-dirty

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Black County family affected by genetic cancer in action plea - Express & Star

Recommendation and review posted by Bethany Smith

Includes oral presentation onProspera test's two-threshold algorithm, showing the combination of donor quantity and donor fraction outperformsdonor fraction alone

AUSTIN, Texas, June 8, 2022 /PRNewswire/ -- Natera, Inc.(NASDAQ: NTRA), a global leader in cell-free DNA (cfDNA) testing, today announced that ithas presented data on the clinical utility of the company's Prospera and Renasight tests in 14 sessions at the American Transplant Congress (ATC) 2022 meeting. This expands on the thirteen peer-reviewed papers that have been published over the last twelve months, demonstrating the strong performance of both assays.

Phil Halloran, M.D., Ph.D., director of the Alberta Transplant Applied Genomics Centre, presented new data on the latest findings of the global, multisite, prospectiveTrifecta study, "Combining fraction and estimated amount of dd-cfDNA to assess kidney transplant rejection using molecular diagnoses and histology." The study demonstrates that the new two-threshold algorithm for the Prospera test - includingboth dd-cfDNA fraction and quantity -performed better than dd-cfDNA percentage alone in detecting active rejection, with an AUC of 0.88 when compared against molecular biopsy assessment and 0.82 when compared against histological biopsy assessment. This analysis in the Trifecta study features 367 fully-biopsy-matched samples from the 22 participating clinics in the U.S. and Europe.

"The data presented at ATC, combined with other important studies, highlight Natera's dedication to innovation and continued leadership in testing for transplant rejection and genetic risks for kidney disease," said Sangeeta Bhorade, M.D., chief medical officer for organ health at Natera. "The evidence continues to support the use of Natera technology for aiding clinicians in making major care decisions for transplant patients."

Data from theTrifecta study was also presented inthree other ATCsessions, and a full listing of Natera's scientific sessions and presence can be found at https://www.natera.com/events/prospera-conference/

About the Prospera test

The ProsperaTM test leverages Natera's core single-nucleotide (SNP)-based massively multiplexed PCR (mmPCR) technology to identify allograft rejection non-invasively and with high precision and accuracy, without the need for prior donor or recipient genotyping. The test works by measuring the fraction of donor-derived cell-free DNA (dd-cfDNA) in the recipient's blood. It may be used by physicians considering the diagnosis of active rejection, helping to rule in or out this condition when evaluating the need for diagnostic testing or the results of an invasive biopsy. The Prospera test has been clinically and analytically validated for performance regardless of donor relatedness, rejection type, and clinical presentation. It has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.

About the Renasight test

The RenasightTM test is a germline genetic test that screens for hereditary causes of kidney disease. It is indicated for patients with diagnosed kidney disease and is run from a patient's blood or saliva sample. Providers can use the Renasight test to identify a genetic predisposition, clarify a clinical diagnosis, or identify the etiology of an unknown kidney disease to help inform medical management. Additionally, genetic counseling and familial testing can be offered based on the test result. The test has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.

About Natera

NateraTM is a global leader in cell-free DNA testing, dedicated to oncology, women's health, and organ health. Our aim is to make personalized genetic testing and diagnostics part of the standard of care to protect health and enable earlier and more targeted interventions that help lead to longer, healthier lives. Natera's tests are validated by more than 100 peer-reviewed publications that demonstrate high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas and San Carlos, California. For more information, visit http://www.natera.com.

Forward-Looking Statements

All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera's plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera's expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, our expectations of the reliability, accuracy and performance of our screening tests, or of the benefits of our screening tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera's recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at http://www.natera.com/investors and http://www.sec.gov.

Contacts

Investor Relations: Mike Brophy, CFO, Natera, Inc., 510-826-2350

Media: Kate Stabrawa, Communications, Natera, Inc., 720-318-4080 pr@natera.com

View original content to download multimedia:https://www.prnewswire.com/news-releases/natera-showcases-leadership-in-transplantation-at-atc-2022-with-new-data-on-its-prospera-and-renasight-tests-301563616.html

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Natera Showcases Leadership in Transplantation at ATC 2022 with New Data on its Prospera and Renasight Tests - BioSpace

Recommendation and review posted by Bethany Smith

Quenton Tompkins family tree is deeply rooted in rural McCormick County, South Carolina.

His grandfather was a sharecropper in McCormick. His mother, who turns 88 this month, grew up as the youngest of 24 children. Branches of aunts, uncles, and cousins now stretch from Florida to Chicago.

And although 48-year-old Tompkins has heard plenty of stories, his family holds its secrets, too.

He didnt know until he was an adult that his grandfather died of leukemia. And hes still unsure if his fathers bout with prostate cancer runs in the family. Tompkins mother and her siblings have dealt with a range of health issues, including diabetes, heart attacks, and strokes, but he still doesnt know what killed his grandmother more than 70 years ago.

Those are questions I go through personally, said Tompkins, a lobbyist for the Medical University of South Carolina. Theres another side to knowing where you come from.

Twenty-two years ago, President Bill Clinton announced the completion of a draft version of the Human Genome Project, a breakthrough he described as the language in which God created life. He predicted that scientists, armed with genetic discoveries, would find cures for Alzheimers disease, cancer, Parkinsons disease, and diabetes in the coming years.

Clintons prediction, of course, hasnt yet come to pass. But researchers in Charleston are hopeful that a large genetics research project underway across South Carolina may help scientists address some of the states persistent health disparities, which disproportionately impact its Black residents and regularly rank among the nations worst.

The university health system intends to enroll 100,000 of South Carolinas 5 million residents in genetic testing over the next four years in hopes of better understanding how DNA influences health. Researchers also want to recruit participants who reflect the diversity of the states population.

Its an ambitious goal. With nearly 27% of South Carolina residents identifying as Black or African American, the MUSC genetics research project, called In Our DNA SC, would if successful accomplish something most other genetics research projects have failed to do. Historically, diverse participation in this type of research has been very low.

Theres a trust factor. Its plain and simple, said Tompkins, who is developing an outreach program for the project.

He referenced Henrietta Lacks, a Black woman in Baltimore whose cells were used without her or her familys knowledge for research purposes by doctors at Johns Hopkins University in the 1950s, and the Tuskegee syphilis study, conducted over nearly 40 years starting in the 1930s. Researchers deceived hundreds of Black men enrolled in the study, telling them they were being treated for syphilis when, in fact, they were left untreated, even after penicillin became widely available.

Those are still fresh in many peoples minds, Tompkins said. Weve come a long way from those stories it doesnt dismiss what happened but there are a lot more controls and oversight in place to ward those things off from happening again.

But its not only history feeding this distrust. Bias and racism evident in medicine today contribute to the problem.

Diversity in genetics research is so low that approximately 90% of participants in projects launched since the first sequencing of the human genome have been individuals of European descent or those who identify as white, said Dr. Shoa Clarke, a pediatric cardiologist and geneticist at Stanford University.

These numbers affect real-life health care. Clarke and others published research last year showing that a DNA-based tool used to assess a patients risk of developing high cholesterol works reliably well only when administered to those of Northern European descent. Thats because the tool was developed using information from genetic bio-banks largely made up of DNA from white people. And aside from a large DNA bank compiled by the Department of Veterans Affairs, this is generally the norm.

Human beings, regardless of race, are more than 99% genetically identical, but small variations and mutations passed down through generations can influence health outcomes in huge ways, Clarke explained.

Genetics is not the cause of health disparities, he said. But as we move toward using genetics in clinical settings, its very possible they could create new disparities.

In South Carolina, health disparities between Black and white patients are already acute, said Marvella Ford, a researcher at MUSCs Hollings Cancer Center in Charleston.

South Carolina compared to the rest of the country were usually in the bottom tier, Ford said. The prostate cancer mortality rate in South Carolina, for example, is 2 times higher for Black men than white men, she said.

When you look at most other chronic conditions, she said, you see the same thing.

She called the genetics project at MUSC a great opportunity to open the doors. Even so, the topic of recruiting Black research participants for genetics studies is complex.

Theres debate on how we should be doing this work, said Shawneequa Callier, an attorney and an associate professor of bioethics at George Washington University. Theres just so much diversity in Africa. Its the cradle of humanity.

Men and women transported to Charleston and other American port cities during the transatlantic slave trade came from a wide region of Africa mostly from West Central Africa, but in large numbers from regions farther north, too. Once in America, they were often separated and forced hundreds of miles apart. This explains why someone whose ancestors lived on one of South Carolinas barrier islands may have inherited different genetic variants than someone from a multigenerational Black family inland in McCormick County, just north of Augusta, Georgia.

Thats also why categorizing genetics research participants simply as Black or African American, without more context, may not yield particularly useful research insights, Callier said.

If you dont study the data and study it well, thats a real dereliction of ethical duty, Callier said.

Those who choose to participate in the MUSC project stand to benefit from it directly, its organizers said. After submitting a saliva sample, each participant will receive a report indicating if they have one or more of three genetic conditions that may put them at a higher risk for heart disease and certain cancers such as one of the BRCA mutations linked to breast cancer. If they test positive for one of these conditions, they will be connected at no cost to a genetics counselor, who can assist with information and treatment options related to a patients inherited risks. Participants will also learn where their ancestors likely lived.

The de-identified DNA data will then be used by researchers at MUSC, as well as those at Helix, a private California-based genomics company, which will process the saliva samples and extract the genetic information from each participants sample. Researchers at MUSC and Helix have indicated they hope to use the results to better figure out how DNA affects population health. Heather Woolwine, an MUSC spokesperson, said the project will cost $15 million, some of which will be paid to Helix. Hospital revenue will fund the research, she said.

Tompkins expects to receive a lot of questions about how it all will work. But hes used to questions. He said he encountered much of the same hesitancy when he helped set up MUSC covid testing and vaccine sites across the state. Many people regardless of race worried microchips or tracking technology had been embedded into the covid vaccines, he said.

Tompkins found that the key to persuading residents in rural parts of the state to consider the covid vaccine was to seek out invitations from trusted, local leaders, then set up events with them. South Carolinas covid vaccination rate remains lower than the national average, but Tompkins said some skeptics have been more receptive to MUSCs message because the hospital system has focused on building relationships with organizers outside Charleston. He hopes to use those relationships to spread word about the new genetics research project.

You have to build those relationships and find community champions that can help you open doors and gather people, he said. Then, its about letting them choose.

Lauren Sausser: lsausser@kff.org,@laurenmsausser

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Addressing the Trust Factor: South Carolina Researchers Tackle Health Disparities Using Genetics - Kaiser Health News

Recommendation and review posted by Bethany Smith

CARMEL, Ind. The founder of the Safe Haven Baby Boxes claims the Department of Child Services is giving a surrendered infant back to his parent without doing a DNA test first.

We cannot be just pretty sure that this is the bio parent, their words, not mine, Monica Kelsey, founder of the Safe Haven Baby Boxes, said in a popular video posted to social media.

Kelsey said she has spoken with a relative of the woman claiming to be the mother of an infant surrendered in a Carmel Safe Haven Baby Box in mid-May. She said the family member says a DNA test has not been done yet the reunification process has started.

Kelsey said the anonymity of these boxes is crucial to this service, and in all cases makes it impossible to figure out who the biological mother is without DNA testing.

No cameras are around these boxes and so, mother or a father places this child inside this box, there is no way for us to know who that parent is, Kelsey said.

The baby boxes are located at fire stations and hospitals around the state. Kelsey said once a baby is placed in the box, they are given medical care and then taken to the states Department of Child Services.

If theyre not going to do a DNA test or a drug test, or vet this family, we know has not happened, Kelsey explained. We have contact with the family. We know this has not happened yet. I have a problem with that. I have to be this little guys voice.

We investigated these claims, and reached out to DCS. The agency said the safe haven law prevents them from discussing a particular case, but they gave us this statement:

A social media post has raised questions regarding the steps the Indiana Department of Child Services takes after a baby is surrendered under theIndiana Safe Havenlaw.

It is common for children to come into DCS care without the identity of one or both parents being immediately known. DCS would never, under any circumstance, send a child home with someone claiming to be their parent without first confirming with certainty that persons relationship to the child. This may include genetic testing, along with many other steps to ensure safe reunification if it is in the best interest of the child. If an individual comes forward claiming parentage, DCS works hand in hand with the juvenile court to determine whether the child was surrendered with the knowing consent of both parents.

Information regarding Safe Haven surrenders is sealed under Indiana law as part of confidential juvenile records, and, with few statutory exceptions, only parties to the case are privy to those details.

Indiana law does not address this specific situation. We know it has captured the attention of State Senator Travis Holdman is aware of this situation and is in communication with DCS.

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Baby Box founder claims infant will be given back to parent without DNA test - FOX 59 Indianapolis

Recommendation and review posted by Bethany Smith

NEW YORK Based on findings from a small pilot study in a relatively well-off patient population in London, a UK team has suggested that a combination of whole-genome sequencing, panel sequencing, and comprehensive medical testing and imaging is feasible in a family practice setting and may benefit patients and their families.

Ros Eeles, a researcher with the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust shared early findings from the study at the American Society of Clinical Oncology's annual meeting in Chicago on Friday. Together with Michael Sandberg, a general practitioner and medical director at the private healthcare center 90 Sloane Street, she co-led the 90S Study, named in a nod to that central London center.

"We had a group of specialists who wanted to look at what would happen if you brought whole-genome sequencing into primary care," Eeles said, noting that the 90 Sloane Street center has built in electrocardiogram, echocardiogram, abdominal and pelvic ultrasound, and routine blood test capabilities.

In the context of cancer, for example, germline and somatic mutations can impact everything from disease screening to treatment strategies, for example. Indeed, large-scale clinical and population sequencing studies looking at germline genetic variation and their ties to human traits or disease are increasingly common, as are efforts to characterize germline and somatic mutations in cancer patients.

But studies on the potential for sequencing individuals in a family medicine setting are much rarer, and it remains to be seen whether the approach is feasible, scalable, cost-effective, and/or beneficial for patients with or without an existing diagnosis.

"What we wanted to ask was, 'Should you use whole-genome screening in next-generation health screening in primary care?'" Eeles said.

For the pilot stage of the study, the team had thirtyfold average whole-genome germline sequencing done commercially on 104 seemingly healthy individuals ranging in age from 29 to 82 years old, who were recruited between 2020 and 2022. The participants tended to have high socioeconomic status and more than 94 percent had a family history of cancer or cardiac disease in a first- or second-degree relative.

All but one of the participants was symptom-free, and 13 had a history of cancer. European ancestry was reported for more than 95 percent of those enrolled.

Since researchers had their sights set on finding as many informative variants as possible, they rounded out short-read genome sequence data with targeted panel sequence data to try to avoid missing deletions. They profiled pharmacogenomics-related variants, polygenic risk contributors, and other genetic features using whole-genome sequence data, which provided insights on up to 566 genes, and used targeted sequence data to search for actionable changes in dozens of cancer- or cardiac-related genes.

The team also considered participants' personal and family health histories, as well as results from a full medical with the same general practitioner. For that medical, participants were profiled with a variety of clinical screens ranging from blood tests to organ imaging.

The team opted to report only variants that could prompt actionable changes to a patient's care, she added, but they established a system for returning to suspicious variants in the genomes as the definition of actionable mutations continues to expand or evolve in the future and new drug targets turn up.

All told, the newly generated genome sequences led investigators to relatively rare, clinically actionable germline mutations in 27 study participants. They flagged cancer-related genetic risk variants in genes in 10 of the participants, for example, while two more individuals carried actionable cardiac rhythm disorder-associated variants, and still other patients had variants in genes involved in clotting, lipid metabolism, or other processes.

Far more individuals around 80 percent of individuals in the study were identified as carriers of variants implicated in autosomal recessive conditions, the team reported, including conditions that are relevant to reproductive screening programs. A significant proportion of sequenced individuals had at least one variant linked to pharmacogenomic responses.

The kinds of risky germline variants detected sometimes tracked with the new diagnoses made or with an individual's personal or family health history, but not always.

The medicals alone led to new heart disease or prostate cancer diagnoses in several study participants. On the other hand, 70 percent of individuals who ended up having cancer susceptibility-linked variants in their germline would not have been found without the genetics program, Eeles said.

"Clearly we are picking up mutations in those without a family history, and that's where geneticists giving advice is going to be important," she explained.

"The majority of patients had a significant change in management for themselves or their families," Eeles and her co-authors wrote in an abstract accompanying the ASCO presentation. "Whole-genome sequencing as part of health screening in family practice is feasible and is likely to have significant beneficial health management implications."

The team tapped into the common variant data collected from participants for a research arm of the study, which looked at polygenic risk for conditions such as colorectal cancer or prostate cancer.

While the research was done within a private clinic setting, the investigators also looked at what aspects of the program might be retained, jettisoned, or tweaked if attempting to apply it through a public health system such as NHS.

Speaking remotely at the ASCO meeting, Fergus Couch, a laboratory medicine and pathology researcher at the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, noted that the 90S Study is "a really nice model for evaluating how exome sequencing, genome sequencing, or panel sequencing might actually be useful in the clinical setting."

For example, he noted that the program picked up risky variants that would have been missed by following current family- or personal medical history-based genetic testing guidelines in the UK.

Still, Couch questioned whether the patient population for the 90S Study was representative of the broader population, since family histories of disease and rates of clinically actionable changes in cancer-related genes such as BRCA1 were higher than that described in the past.

He also noted that care is needed in general when incorporating sequencing into clinical care for symptom-free individuals, not only when it comes to defining actionability or implementing information on specific variants or risk scores but also when selecting the sequencing strategy used and setting up appropriate referrals for patients with actionable variants or recessive disease carrier status.

"Could this type of sequencing and the data that comes from it actually be handled by general medicine, family medicine, or community practices around the country? Is this really just too much?" he wondered, noting that "in the absence of a very strong referral network, this could be really quite challenging for the vast majority of non-tertiary medical centers."

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UK Team Tests Whole-Genome, Targeted Sequencing in Family Practice Setting - GenomeWeb

Recommendation and review posted by Bethany Smith

Published

2022-06-08 14:56

2:56

June 8, 2022

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Almost 20 years ago, Italy tested what it would look like if embryos were given the same rights as a living person. The country put stringent limits on in vitro fertilization treatments (IVF), banning embryo preservation, limiting the number of embryos created a time to three and mandating that they all be transferred to the uterus.

In the years the law was in place, before it was ultimately repealed in full, more IVF treatments failed, more pregnancies resulted in no live births or more multiple births, and IVF became more difficult to access and more expensive. Italian patients who could afford it traveled to other countries across Europe to receive treatment. Success rates at IVF clinics dropped, high-risk pregnancies increased and doctors had to risk transferring embryos that could lead to medical complications for the pregnant person. Single parents and many LGBTQ+ parents couldnt access IVF at all because surrogacy and sperm donation were also banned.

To doctors in the United States, Italy was an extreme example of what could happen if embryos were treated as people, even though in most cases both in the lab and in nature a large portion of embryos never become babies. Now, theyre worried that the increased barriers and cost that doctors saw in Italy is a preview of what could happen in the United States.

Any day now, the Supreme Court is likely to overturn its 1973 Roe v. Wade decision, according to a draft of the decision leaked in May, leaving the choice of how to limit abortion access up to states. The impact is expected to trickle down to fertility treatments. States including Louisiana, Nebraska and Oklahoma have tried to pass abortion restrictions that revise the definition of life to begin at fertilization and that limit or ban discarding embryos, creating the standard that led Italy to impose its IVF restrictions in 2004. While those efforts have so far failed, states are expected to try again if Roe is overturned.

Not only could a decision like that impact patients health, but it could take a procedure that is already prohibitively expensive for many families and make it even less accessible, reproductive endocrinologists told The 19th.

Already, one cycle of IVF in the United States runs patients about $23,000 on average. Most patients will go through two or more cycles before they have a successful pregnancy, a cost of about $50,000, according to FertilityIQ, which collects IVF cost data.

In a typical cycle here, IVF involves extracting 10 to 15 eggs for fertilization and testing the embryos before choosing typically one for transfer to the uterus. The rest are often frozen, donated or discarded. That approach has led to high success rates for IVF, fewer transfers, and fewer high-risk pregnancies and losses.

Limiting the number of eggs that can be extracted in a cycle, limiting genetic testing or banning embryo preservation means the likelihood that IVF treatments are successful will decrease. That means patients will have to endure and pay for more IVF transfers, and doctors will have to assume potential risks if faced with decisions about eliminating embryos.

The issue is also one of racial justice.

The fertility industry is one where the typical patient is somebody who has money, typically White, a little bit older. [It] has already been catering to a narrow population, said Kimberly Mutcherson, the dean of Rutgers Law School and a reproductive justice scholar. The majority of low-income workers are women of color, and low-income women are also most likely to have Medicaid coverage, which is prohibited from covering abortion care and does not cover IVF. Mutcherson points out that while they wont pay for IVF, most state Medicaid programs do cover some form of sterilization.

According to a survey of nearly 1,500 fertility patients published in 2020, more than 75 percent of IVF patients are White and more than 80 percent have annual household incomes higher than $100,000. Black women are the most likely to report facing barriers to fertility treatment, and Black and Latina women traveled twice as far as White and Asian women for treatment.

Low-wage people of color, who already have the least access to fertility care, are the same people who have the least access to abortion care.

That limited access is now under siege on both ends, said reproductive endocrinologists and IVF experts, if treatments become more costly.

Patients with the means to do so may move to states with more expansive laws for IVF, and doctors in states that might restrict IVF will move to states where they can continue to practice, said Dr. Lora Shahine, a reproductive endocrinologist at Pacific NW Fertility in Seattle and host of the Baby or Bust Podcast. That will result in further limiting access to patients, particularly in states in the South where the majority of low-wage women of color are concentrated and where most of these personhood bills have been introduced.

Dr. Robert K. Hunter II, the practice director at Kentucky Fertility Institute in Louisville, said the fear of losing his job and having to potentially move to another state is very real for him. Kentucky has tried to pass a personhood bill in the past, and its one of 13 states with a trigger law that would ban abortion immediately if Roe is overturned.

If doctors are limited in the number of eggs they can fertilize, whether or not they can perform genetic testing or whether they can cryopreserve eggs the same limitations Italy imposed that could increase the number of IVF cycles patients have to undergo to have a successful pregnancy, and it can increase risk for doctors, he said.

The cost of continuing to do business will increase for providers, and that will absolutely get passed down to patients, Hunter said. And not to mention if we cant do genetic testing and cryopreservation thats a lot of added cost and disappointment and emotional cost with that, as well.

Hunter said that if that happened, he would become only one piece in a complex IVF process that could see patients seeking care in multiple states.

For me to become someone that is just making embryos to ship them to Illinois or wherever the closest women-friendly state is Is that a sustainable business for me? If I just become a monitoring center for a practice that can still perform IVF for another state? I dont know that thats a viable practice model for me, he said. I dont know what is coming down the pike. I will certainly do my best to fight for my patients, but at the same time, in all my years of medical school, residency training, fellowship training, I never thought Id be affected. That wasnt part of the gig.

IVF is still protected, doctors stressed, but they have also started to think about what could happen in a world where its not.

In Nebraska, Dr. Stephanie Gustin knows it could become a reality. In April, the state tried to pass an abortion bill that redefined life as beginning at fertilization. It lost by two votes. Republican Gov. Pete Ricketts has indicated that if Roe v. Wade is overturned, he will call a special session this summer to reintroduce the legislation. Gustin is part of a coalition of doctors working to inform legislators about the implications such a bill would have for fertility care.

Gustin, who is the medical director of the Heartland Center for Reproductive Medicine in Omaha, one of only two fertility clinics in the state, is conflicted about what to do if it passes.

I made this promise to do no harm. Why would I provide my patient with substandard care that, if they could drive to Colorado or Minnesota they could get the standard care of IVF, just to keep my business alive? I wouldnt be able to sleep at night, Gustin said. The problem is that by not having a fertility clinic here, there will be many people who cant seek IVF care, period. Those people may be like, We would rather have something than nothing. She hasnt yet figured out how she would navigate that.

Programs that provide grants and loans to families seeking IVF treatment are also teasing out how it could impact them and the people they serve. Many of those programs were born of former IVF patients who have faced the challenges of cost firsthand.

Teresa Barbosa, the CEO of Gift of Parenthood, a program that awards quarterly IVF grants to families in financial need, said she created the program in 2019 after spending more than $60,000 her life savings on ultimately unsuccessful IVF treatments.

Gift of Parenthood awards grants as high as $20,000 four times a year; more than 15 babies have been born as a result of the treatments they helped facilitate. Many of those who come seeking help are women of color, like her, who are running out of options, Barbosa said.

They dont have the access its really scary, she said. Gift of Parenthood this year added a fundraising feature on its site to help families raise funds for their procedures, as well as a response to the degree of need.

She feels in limbo, Barbosa said, facing the possibility that even more people will need help paying for IVF and she will be able to help an even smaller slice.

Fertility loan providers like EggFund, which helps streamline the application process for IVF patients, already makes accessing loans easier for patients through one application that ensures the money goes to them and not a clinic. That could help in the case that a clinic closes in a state with changing IVF laws, said founder Carmela Rea. EggFund also allows participants to apply with other people, including siblings and parents, to help reach the requirements for a loan. But higher IVF costs will likely mean higher loans and more debt.

Rea created EggFund in 2017 after spending $80,000 of her savings on her own IVF treatments.

I felt it was wrong that only the wealthy could procreate, and I think its a human right if you want to have a family to be able to have it and not to have money be the consideration that decides whether you can have a family if you want it or whether you can end a pregnancy if you dont want it, Rea said. It shouldnt come down to your wealth.

Already insurance coverage for IVF is limited at best and nonexistent at worst. Few employers cover it, and those that do are typically larger companies that employ higher-paid workers, like major tech companies.

At the Baby Quest Foundation, one of the most well-known IVF grant programs in the country, founder Pamela Hirsch said she is working to get more employers to cover IVF. Hirsch has helped give 200 grants since launching in 2012 after her own daughter underwent four unsuccessful IVF cycles before welcoming two babies via surrogates.

Abortion restrictions could make it less likely for employers to include IVF coverage in their insurance plans, experts said.

Its almost like a collision course: Which direction is fertility moving in? More access to care because people will be lucky to have insurance coverage from their work or the whole industry closing down? Hirsch said.

Currently, New York requires that large-group insurance policies cover three rounds of IVF. That law leaves out Medicaid patients and those who work for employers with fewer than 100 employees, an estimated 2 million New Yorkers, said Risa Levine, an infertility advocate and former member of the board of directors at RESOLVE: The National Infertility Association, who helped pass the legislation in New York.

She spent $270,000 on fertility treatments.

As a White Jewish woman whose parents wanted her to have a kid, I was able to borrow money from my parents, Levine said. But, it absolutely impacted my financial security. It put me in a precarious financial situation.

Low-income women wouldnt even have that choice, she said. And insurance providers are going to reflect the new risk brought on by changes that redefine how IVF can be performed.

What insurance company is going to cover a clinic and a doctor for malpractice or for criminal behavior if they define life as beginning at conception outside of the womb? Levine said.

For providers, the entire discussion puts into question all the advancements IVF has made scientifically and politically in recent years.

There are numerous questions and few answers. What will happen to the pace of scientific discovery if fertility clinics close and IVF becomes a niche service? What will happen to patients, if companies are less willing to cover IVF and conversations about insurance covering the procedure die out?

We are so far from one another, Shahine said, and I feel like any restrictions are going to make those gains weve already made fall backward.

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Many low-income people are already shut out of IVF. Could abortion bans make it even more expensive? - The 19th*

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With a history of breast cancer in her family, Andrea Cronin has been careful to get annual mammograms since she was in her early 30s.

Like a lot of women, though, she skipped the test in 2020 due to the pandemic. She was relieved when her 2021 test came back negative, but she wanted more reassurance. Cronins mother was diagnosed with breast cancer 28 years ago, and the cancer has since metastasized to her stomach and bones. Cronin also has dense breasts, which can make reading a mammogram more difficult.

With my mothers history, I just wanted to be proactive, recalled Cronin, 47, who is from Haddonfield. My doctor suggested alternating mammograms and MRIs every six months.

This past January, Cronins MRI showed a tumor, which was confirmed by an ultrasound. She was diagnosed with stage II invasive ductal carcinoma.

Cronins hunch that she needed further testing paid off. Not waiting another year to find the cancer means her prognosis is good, said Zonera Ali, Cronins oncologist at the Lankenau Institute for Medical Research.

But her situation is unusual, her doctor and experts stressed.

Most patients cancers are picked up on the mammogram, but about twice a year I see a patient whose cancer is found through the MRI, said Ali. When cancers are detected earlier, chances of cure are much higher.

For Cronin, getting additional testing made sense, given her mothers bouts with breast cancer. But that is not advised for women without a family history of cancer. The increased sensitivity that MRIs offer can show something that looks like a problem but may not actually be a problem, said Richard Bleicher, leader of the Breast Cancer Program and professor of surgical oncology at Fox Chase Cancer Center.

MRIs can result in three times more unnecessary biopsies than mammograms, he noted.

We end up doing a lot of biopsies, more testing and interval testing, and sometimes unnecessary surgeries that cause pain and discomfort for women, not to mention costs and anxiety, he said.

When Cronins cancer was detected, she was given the option of having a lumpectomy, in which just the lump and surrounding tissue would be removed, but opted to have both breasts removed in a double mastectomy, given her mothers history of recurrence.

This would require only one surgery and get me back into my life of dentistry quicker, Cronin said.

Her mother, Joyce Makarczyk, was first diagnosed with breast cancer through a routine mammogram in 1993, at the age of 46.

I was going to go for a second opinion but the doctor said it was an aggressive cancer so I shouldnt waste any time, recalled Makarczyk, who lives in Mays Landing. Cancer was also discovered in her lymph nodes, so she had one breast removed, followed by chemotherapy and radiation.

About 10 years later, the cancer returned in her right breast. She had a lumpectomy and radiation and was cancer-free for five years. But then she started having stomach problems. The cancer had metastasized into her stomach and bones.

READ MORE: Maria Quiones-Snchez went public after being diagnosed with breast cancer. Now she begins the next chapter of her story. | Helen Ubias

Makarczyk, now 75, has taken the targeted therapy Ibrance ever since and has PET scans every six months. A couple of times, the scan showed cancer cells in her stomach, which were surgically removed.

Im feeling OK, she said. The cancer doesnt cause me any trouble at all.

During Cronins double mastectomy in March, cancer was found in one of the 11 lymph nodes tested. In late April, she started eight sessions of chemotherapy over four months, which will be followed by one month of radiation.

Once cancer escapes into the lymph nodes, the chance of that cancer going somewhere else is higher, said Ali. Especially in women below the age of 50, we recommend chemotherapy and post-mastectomy radiation.

After Cronins cancer diagnosis, her older sister Erica Toffenetti also is seeking additional screening.

The fact that my sister showed no symptoms, it wouldnt hurt to have these tests done for a baseline, said Toffenetti, 51, from Buena, N.J. Im feeling a little nervous but also more relieved. With my mother Ive been dealing with breast cancer more than half my life.

Toffenetti, who has two children, had genetic testing done in 2012 and again in 2019 as the testing became more advanced. Like her sister, she doesnt have the BRCA gene associated with higher risks of cancer.

Both sisters have dense breasts, as do nearly half of all women age 40 and older who get mammograms, according to the NIH. Dense breasts have relatively high amounts of glandular tissue and fibrous connective tissue, which make it more difficult to see potential tumors.

The American Cancer Society recommends mammograms as a choice for women aged 40 to 44. Women aged 45 to 54 should get a mammogram every year; and women 55 and older should switch to a mammogram every two years, or can continue yearly screening.

At this time, experts do not agree what other tests, if any, should be conducted in addition to mammograms in women with dense breasts, according to the American Cancer Society website.

ACS recommends mammograms for dense breasts without any other high-risk factors, said Karen E. Knudsen, chief executive officer of the American Cancer Society and former enterprise director of the Sidney Kimmel Cancer Center at Jefferson Health.

When Renee Anderson, Cronins ob/gyn at Pennsylvania Hospital, sends mammogram results to patients with dense breasts, she includes an explanation of what it means.

In those cases, Anderson gives her patients the option for more testing, and about half, most often those with a family history of cancer, choose to have an MRI or ultrasound.

When you get a discrepancy like what you have with Andrea, it could have been missed because of dense breasts, she said. Or whats more worrisome is that you could have a very aggressive form of cancer that started quickly and is growing quickly.

READ MORE: The war on cancer at 50: How a socialite citizen-lobbyist started a movement

Cronin, whose cancer is slow growing, was fortunate that her insurance covered the MRI. Thats not the case for every woman. In 2020, Pennsylvania Gov. Tom Wolf signed into law legislation requiring insurers to cover breast MRIs or ultrasounds for women at increased risk of breast cancer. But the patient still may be responsible for co-pays and deductibles, which can be costly.

Anderson stressed that the most important form of self-care is seeing your gynecologist and having a mammogram annually, especially for older women. The ACS guidelines say screening should continue as long as a woman is in good health and is expected to live 10 more years or longer.

For some women as they get older, 50 and above, they dont think they need to come to a gynecologist, so nobody is doing an exam, she said.

Breast cancer is associated with the BRCA1 and BRCA2 genes, but just 0.25% of the general population who have breast cancer have the BRCA gene, said Ali, Cronins oncologist. That number jumps to 2.5% among Ashkenazi Jewish women.

With an 11-year-old daughter, Cronin was eager to have genetic testing. She was tested for 35 different genes related to an increased risk for certain cancers and was negative for all of them, including the BRCA genes.

Unfortunately, I feel that I still have to worry about her, because I dont have the gene but still got cancer, she said.

Cronin shared her experience in an email to her dental patients, alerting them to the fine print disclaimer at the bottom of some mammogram reports that says extreme breast density decreases the sensitivity of mammograms. Please discuss family history and any concerns with your provider.

So many patients have thanked me directly for being so transparent with them, Cronin said. Specifically, two patients told me that after sharing my emails, their mothers demanded more testing after first being told no. Its so important to be your own patient advocate.

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An MRI detected breast cancer in this Haddonfield woman. Should you consider having one? - The Philadelphia Inquirer

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Four years ago, Annik Greenhill discovered she had an inherited mutation of the BRCA1 gene, which predisposes her to breast cancer.

While discovering the gene potentially saved her life, it led to challenges with insurance that have left her in a difficult position.

Insurance companies were concerned the BRCA1 gene made her high risk, and she had to be on a premium health insurance plan to be covered, she said.

In New Zealand insurance companies are allowed to ask to see the results of genetic tests, which has led to accusations of discrimination.

READ MORE:* Beware of DNA health tests by ancestry companies* Preventative double mastectomy worth it for mum-of-two living with the BRCA gene mutation* I tried to ignore genetic warnings about cancer, and that could have been fatal

After returning to New Zealand, Greenhill struggled to find an insurance company willing to cover the gene. Her insurance broker told her most insurers would exclude any treatment relating to the gene, or only cover her after prophylactic surgeries were undertaken.

Abigail Dougherty/Stuff

Annik Greenhill is a BRCA1 carrier and has been affected by genetic discrimination as a result.

I thought the fact I know I am a carrier should in some ways reduce my overall risk to an insurance company because I am in an early detection programme, I was a carrier whether I knew it or not.

Breast Cancer Foundation NZ chief executive Ah-Leen Rayner said insurance discrimination around the BRCA gene was a serious problem, and a law change was needed.

So long as New Zealand insurers are able to ask about genetic test result, people with the BRCA gene will be discriminated against, even though they might not get breast cancer.

Greenhill eventually took out an UltraCare policy with Southern Cross, the only insurer who would offer coverage related to the gene, she said.

However, had to be on the second-highest plan, and only after a three-year stand down period would she be eligible for BRCA related covershe said.

Health insurance cost the family $580 a month, a significant expense, she said.

Southern Cross said that it would cover cancer treatment without a stand down period. But because she already knew she had BRCA1, she would not be covered for monitoring the gene or for prophylactic treatment for three years.

She also applied for additional chemotherapy cover of $300,000 a year, but was capped at $60,000.

Southern Cross said while Greenhill would not be excluded from taking out a Chemo 300 plan, she would need to meet the terms and conditions, which included possible exclusions for family history.

ROSA WOODS/STUFF

Ashleigh Stallard has the BRCA gene and was faced with a strong risk of developing breast cancer. She chose to have a preventive mastectomy at age 23. (Video first published in October 2019)

While grateful Southern Cross offered some cover, she said it still felt like she was being punished for gaining a better understanding of her health.

Greenhill did not regret her decision to get tested, but was concerned others in her position would be discouraged because of the genetic discrimination she encountered.

Its a conundrum that Georgia Eve, a 22-year-old social support worker, is grappling with.

She was planning to donate one of her eggs to a fertility organisation, until she heard it could lead to genetic discrimination from insurers.

Egg donors are required to take a genetic test as part of predonation health checks. But potential donors are told the results of that test can be legally asked for and used by insurers in underwriting decisions.

Despite having wanted to donate an egg for some time, the potential for genetic discrimination in later life was a dealbreaker, Eve said.

Its a bit of a risk to take. I am someone who wants to travel, so I am concerned about affording access to travel insurance later in life. I am thinking it might be better not to do it, she said.

Eve said insurers position on genetic testing was affecting broader public health.

If people are being dissuaded by insurance companies not to get genetic testing, they are losing an opportunity to live healthier lives. But as it stands many people are choosing not to know.

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Georgia Eve had been considering donating an egg to a fertility service. But to do so she would have had to undergo a genetic test, and in New Zealand an insurance company can ask to see the results.

A United States survey found 28% of participants declined genomic testing because of concerns about insurance discrimination, the New Zealand Medical Journal reported recently.

But Australia and Canada are legislating to protect individuals from genetic discrimination by insurance companies.

Canada, in 2017, introduced a complete ban on the use of genetic test results to discriminate, including for insurance and employment.

The Australian life insurance industry, in 2019, introduced a five-year ban on the use of genetic tests in underwriting.

New Zealand insurance companies have not followed suit.

Auckland University Centre for Cancer Research acting director Professor Andrew Shelling said New Zealand was a significant disparity from other first-world countries in the way it handled genetic information.

People should be very concerned about insurers using genomic information, and the patient advocacy group Against Genetic Discrimination Aotearoa, was calling for a complete ban, Shelling said.

Genetic testing allowed people to make informed health care decisions, and people were refusing to undergo testing because of the potential insurance consequences, he said.

For people who are at risk of genetic conditions, choosing not to be tested may have serious health impacts.

While there was no New Zealand data to draw from, he believed it would be similar to the rest of the world, where between 10% and 30% of people were declining testing.

Thats an extraordinary number of people and is likely to be having a significant impact on people at risk of serious genetic disease.

Southern Cross chief sales and marketing officer Kerry Boielle said it did not add a pre-existing condition exclusion as a result of a genetic abnormality, and typically would not increase premiums or refuse to issue a policy based on that information.

However, it may exclude any consultations, further tests, or treatment required in its policy as a result of an abnormality.

Southern Cross said that in the past five years, 51 members had disclosed a genetic abnormality or mutation, and 51 people had exclusions applied to their policy as a result of genetic abnormalities.

Three other insurance companies said they were members of the Financial Services Council (FSC) and complied with the councils code of conduct and guidelines around genetic tests.

FSC chief executive Richard Klipin said the issue of genetic testing was complex.

To ensure that insurance remains sustainable and fair for all customers, some insurers may ask customers to disclose known information about the results of their genetic tests, Kiplin said.

But, insurers were never asked to carry out genetic testing, he said.

CORRECTION: An earlier version of this article stated Southern Cross required a stand down period of three years before it would cover cancer related to the BRCA1 gene. However, the stand down period relates to prophylactic treatment. (Amended at 12.54pm on June 8, 2022)

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Kiwis should be 'very concerned' about genetic discrimination - Stuff

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The novel coronavirus SARS-CoV-2, which causes COVID-19, has caused millions of infections worldwide. As time has passed, it has become increasingly clear that COVID-19 is not a cookie-cutter disease.

People vary significantly in their susceptibility to infection, symptoms, and disease severity. Certain risk factors clearly play a role. Could genetics also play a part?

Researchers are examining the role of genetics in peoples reactions to the virus. While far from conclusive, data indicates that some of your genes may influence how SARS-CoV-2 affects your health.

Read on to learn what research has uncovered.

To look for genes that may influence the impact of COVID-19, geneticists scan the DNA of large study groups. This helps them find and identify connections between specific DNA sequences and disease characteristics.

Early genetic studies have uncovered compelling clues that certain genomic variants and blood types may play a role in how people react to the SARS-CoV-2 virus.

Angiotensin-converting enzyme 2 (ACE2) receptors are proteins found on the surface of certain cells. ACE2 receptors generate other proteins that regulate cell function. ACE2 receptors also allow the SARS-CoV-2 virus to enter your cells.

ACE2 receptors are located in the lungs, blood vessels, kidneys, and other parts of the body. They help regulate blood pressure, wound healing, and inflammation.

Everyone has ACE2 receptors, but their amount and locations vary. Multiple studies, including a 2021 study reported in the European Journal of Medical Research, found a link between ACE2 levels and vulnerability to COVID-19.

The same study also found that people with a specific type of genetic variation in ACE2 are at higher risk of SARS-CoV-2 infection. Another finding was a heightened susceptibility to SARS-CoV-2 infection in men compared to women.

Cytokines are proteins released by cells. Cytokines help cells communicate with each other. They also work to regulate inflammation and the bodys immune response to infection.

A cytokine storm is an overreaction of the immune system to infection from an invading host, such as SARS-CoV-2. During a cytokine storm, your cells release too many cytokines. This causes high levels of inflammation and the overactivation of certain immune cells.

The results of a cytokine storm can be severe and include tissue damage, organ failure, and sometimes death.

A review of multiple studies found that several genetic variants in cytokine genes may be related to cytokine storm and disease severity. Studies also found that these variants might be related to COVID-19 complications, including venous thrombosis.

A large study analyzed genes found along a stretch of chromosome 3. The study found compelling information about specific genes and their potential impact on respiratory failure caused by COVID-19.

Researchers identified a gene cluster on chromosome 3 linked to susceptibility to respiratory failure in COVID-19 patients. According to researchers, the gene cluster confirmed that ABO blood type played a role, indicating a higher risk for respiratory failure from COVID-19 for people with type A blood.

The HLA gene helps regulate your bodys immune response. Decades of research have found that people with certain HLA alleles (slight gene mutations, or variations) are prone to various autoimmune, inflammatory, and malignant diseases. Scientists call this phenomenon HLA disease association.

A 2021 review found that people with certain HLA alleles were more vulnerable to COVID-19 and severe illness than the general population.

If you were assigned male at birth, you might be at higher risk for serious illness from COVID-19. While some data points to lifestyle factors more common in men (such as smoking or drinking alcohol), genetic factors are also at play.

Men tend to express higher amounts of ACE2, making them more susceptible to COVID-19. A 2021 study suggests that this alone doesnt account for the difference in response.

The study also highlights genes present in men that might make them more prone to infection and genes present in women that may help them fight off infection.

There are also genes on the X-chromosome that influence your immune response. There are about 55 times as many of these genes on the X-chromosome as on the Y-chromosome.

As men only have one copy of the X-chromosome, variants in genes on this chromosome may have a greater effect on how COVID-19 progresses.

Its also important to remember that genetic traits are sometimes clustered among people with the same nationality, ethnicity, or culture. This can skew study results, especially in places where poor living conditions or poverty are factors.

Still, three 2021 studies (1, 2, 3) state that we cant ignore ethnic differences in COVID-19 susceptibility. Some genes that influence the course of COVID-19, such as HLA alleles, are more prevalent in certain ethnicities.

Another study noted that Black people tend to have more variations in the genes that affect ACE2.

Again, more research is needed before we fully understand the true impact.

COVID-19 is known to present with a wide variety of symptoms. While some symptoms are common, the virus tends to affect people in many different ways. Your genetics may play a role here too.

A 2021 study linked COVID-19 with altered gene expression in specific tissues or cells. This suggests that certain genetic variations may make you more likely to experience certain symptoms.

The study also noted that some of the genes they studied were also linked to ethnicity. This means that some symptoms may be more common in certain ethnic groups.

Researchers and geneticists are sharing their findings on genetics and COVID-19 through the COVID-19 Host Genetics Initiative.

As more studies take place, the biological pathways that affect your susceptibility or natural immunity to this disease may become more apparent.

This research may help generate new types of drugs that can treat COVID-19. It may also help determine why some people have a severe reaction to infection, and others experience mild to no symptoms.

While exciting and compelling, its important to remember that the research on genetics and COVID-19 is still new. We need more research before we can fully understand the impact of genes on this disease.

Knowing your risk factors can help you make decisions concerning exposure to the virus. Risk factors for COVID-19 and severe symptoms include:

No gene makes you fully immune to COVID-19. No matter what your own risk may be, these measures can help protect you from infection:

A growing body of evidence has linked certain genes and gene mutations to COVID-19 susceptibility. While compelling, this information is still new. We need more research to fully understand how our genes affect our response to the coronavirus.

As this body of science grows, it may better inform us on how to treat or even prevent COVID-19.

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Genetic Susceptibility to COVID-19: What We Know So Far - Healthline

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Height is typically a predestined characteristic in most people. According to Medical News Today, up to 80% of someone's height is based on their DNA. If you come from a tall or short family, you are more likely to be taller or shorter. Yet despite baseline genetics, there are a variety of actions to take during childhood and teen years to ensure that your reach your maximum potential height according to your DNA.

Basically, it's the health advice you've likely heard several times before but not everyone follows. Obey a nutritious dietby eating lots of fruits and veggies every day. Make sure you have enough calcium to grow healthy bones as well as plenty of protein. Get adequate exercise to strengthen bones and muscles.

One of the biggest things teens need to reach optimal height is sleep. A growth hormone is released while you're in certain sleep stages (via Verywell Health). If sleep is insufficient, a body won't likely reach maximum growth.

There are numerous ways to predict how tall a boy will be as he grows. The Mayo Clinic outlines two different techniques. In the first prediction, add the mother's height to the father's height and then add 5 inches for boys. (Subtract 5 inches for girls). Then just divide by two. The second way to estimate height is to find a boy's height at age 2 and then double it. (For girls, do the same at age of 18 months.)

As a general rule, men stop growing when they're 18. There is a slight possibility that if a teen boy began puberty late, he may grow a bit in his early 20s, but that is unusual. The reason is simple and it has to do with growth plates (via Healthline). That's the area of the bone made of cartilage that continues to grow. However, they meld together right after puberty, meaning there is no more potential to grow once they have fused.

Over the years the average height of men has grown and that's because men are now getting better nutrition, exercise, and sleep both as children and teens. In the early 1900s, men were averaging 5 feet, 8 inches tall (via A Hundred Years Ago). Currently, in the United States, the average height for men is approximately 5 feet, 9 inches tall, according to the Centers for Disease Control and Prevention (CDC)while the average weight for menrests at 197.9 pounds.

Oddly enough, there are certain states where heights differ. According to the World Population Review, the U.S. states with the tallest men, averaging 5 feet, 10.8 inches or more, are Alabama, Iowa, Kentucky, Montana, Nebraska, North Dakota, South Dakota, Tennessee, Utah, West Virginia, and Wyoming. The states with the shortest average male heights, averaging below 5 feet, 10 inches, are New York, New Jersey, California, Nevada, New Mexico, Hawaii, and Texas. All the remaining states lie somewhere in between.

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What Is The Average Height For Men In The US? - The List

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Participants

For factor analyses, we restricted our analyses to autistic individuals from the SSC and SPARK cohorts. Participants had to have completed the two phenotypic measures (details are below) to be included in the factor analyses. We also excluded autistic individuals with incomplete entries in either of the two measures (n=5,754 only in the SPARK cohort). This resulted in 1,803 participants (n=1,554 males) in the SSC, 14,346 participants (n=11,440 males) in SPARK version 3 and 8,271 participants (n=6,262 males) in extra entries from SPARK version 5 (SSC, mean age=108.75 months, s.d.=43.29 months; SPARK version 3, mean age=112.11 months, s.d.=46.43 months; SPARK version 5, mean age=111.22 months, s.d.=48.19 months). Only the SCQ was available for siblings in the SPARK study.

We conducted analyses using data from four cohorts of autistic individuals: the SSC (n=8,813)30, the Autism Genetic Resource Exchange (AGRE, CHOP sample) (nmax=1,200)64, the AIMS-2-TRIALS Longitudinal European Autism Project (LEAP) sample (nmax=262)65 and SPARK (n=29,782)31. For sibling comparisons, we included siblings from the SSC (n=1,829) and SPARK (n=12,260) cohorts. For trio-based analyses, we restricted to complete trios in the SSC (n=2,234) and SPARK (n=4,747) cohorts. For all analyses, we restricted the sample to autistic individuals who passed genetic quality control (QC) and who had phenotypic information.

We conducted factor analyses using the SCQ29 and the RBS28. The SCQ is a widely used caregiver report of autistic traits capturing primarily social communication difficulties and, to a lesser extent, repetitive and restricted behaviors29. There are 40 binary (yes-or-no) questions in total, with the first question focusing on the individuals ability to use phrases or sentences (total score, 039). We used the Lifetime version rather than the current version as this was available in both the SPARK and SSC studies. Of note, in the Lifetime version, questions 119 are about behavior over the lifetime, while questions 2040 refer to behavior between the ages of 4 to 5 years or in the last 12 months if the participant is younger. We excluded participants who could not communicate using phrases or sentences (n=217 in the SSC and n=17,092 in SPARK) as other questions in the SCQ were not applicable to this group of participants. The RBS is a caregiver-reported measure of presence and severity of repetitive behaviors over the last 12 months. It consists of 43 questions assessed on a four-point Likert scale (total score, 0129). Higher scores on both measures indicate greater autistic traits.

We conducted exploratory factor analysis on a random half of the SSC (n=901 individuals, of which 782 were males) using promax rotation to identify correlated factors as implemented by psych (ref. 66) in R. We conducted three sets of exploratory correlated factor analyses: for all items, for social items and for non-social items. Previous studies have provided support for a broad dissociation between social and non-social autism features12,23 and have conducted separate factor analyses of social (for example, refs. 67,68) and non-social autism features (for example, refs. 69,70). Thus, we reasoned that separating items into social and non-social categories might aid the identification of covariance structures that may not be apparent when analyzing all items together. We divided the data into social (all of the SCQ except item 1 and nine other items and item 28 from the RBS) and non-social (nine items from the SCQ (items 8, 11, 12 and 1418) and all items from RBS except item 28) items, which was carried out after discussion between V.W. and X.Z. The ideal number of factors to be extracted was identified from examining the scree plot (Supplementary Fig. 2), parallel analyses and theoretical interpretability of the extracted factors. However, we examined all potential models using confirmatory factor analyses as well to obtain fit indices, and the final model was identified using both exploratory and confirmatory factor analyses.

We then applied the model configurations from promax rotated exploratory factor analysis for bifactor models to explore the existence of general factor(s). In addition to a single general factor bifactor model, we divided the data into social and non-social items as mentioned earlier and applied bifactor models separately for the social and non-social items. Hierarchical values and explained common variances were then calculated for potential models as extra indicators of the feasibility of bifactor models, but hierarchical values were not greater than 0.8 for most of the models tested, and explained common variances were not greater than 0.7 (refs. 71,72,73) for any of the models tested (Supplementary Table 2).

Three rounds of confirmatory factor analyses were conducted: first for the second half of the SSC, followed by analysis of SPARK participants whose phenotypic data were available in version 3 of the data release and, finally, analysis of SPARK participants whose phenotypic data were available only in version 4 or version 5 of the data release and not in the earlier releases. To evaluate the models, multiple widely adopted fit indices were considered, including the comparative fit index (CFI), the TLI and the root mean square error of approximation. In CFA, items were assigned only to the factor with the highest loading to attain parsimony. We conducted three broad sets of confirmatory factor analyses: (1) confirmatory factor analyses of all correlated factor models, (2) confirmatory factor analyses of the autism bifactor model and (3) confirmatory factor analyses of social and non-social bifactor models. For each of these confirmatory factor models, we limited the number of factors tested based on the slope of the scree plots and based on the number of items loading onto the factor (five or more). For the confirmatory factor analyses of social and non-social bifactor models, we iteratively combined various numbers of social and non-social group factors. In bifactor models, items without loading onto the general factor in the correspondent EFA were excluded. Items were allocated to different group factors, which were identified based on the highest loading (items with loading <0.3 were excluded). Due to the ordinal nature of the data, all CFAs were conducted using the diagonally weighted least-squares estimator (to account for the ordinal nature of the data) in the R package lavaan 0.6-5 (ref. 74). We identified the model most appropriate for the data at hand with TLI and CFI>0.9 (TLI and CFI>0.95 for bifactor models), low root mean square error of approximation and good theoretical interpretability based on discussions between V.W. and X.Z. Additionally, as sensitivity analyses, the identified model (correlated six-factor model) was run again with two orthogonal method factors mapping onto SCQ and RBS-R to investigate if the fit indices remained high after accounting for covariance between items derived from the same measure, as these measures vary subtly during the period of time evaluated. We also reanalyzed the identified model after removing items that were loaded onto multiple factors (>0.3 on two or more factors) to provide clearer theoretical interpretation of the model. For genetic analyses, we used factor scores from the correlated six-factor model without including the orthogonal method factors and without dropping the multi-loaded items.

QC was conducted for each cohort separately by array. We excluded participants with genotyping rate <95%, excessive heterozygosity (3s.d. from the mean), non-European ancestry as detailed below, mismatched genetic and reported sex and, for families, those with Mendelian errors >10%. SNPs with genotyping rate <10% were excluded, or they were excluded if they deviated from HardyWeinberg equilibrium (P<1106). Given the ancestral diversity in the SPARK cohort, HardyWeinberg equilibrium and heterozygosity were calculated in each genetically homogeneous population separately. Genetically homogeneous populations (corresponding to five super-populations: African, East Asian, South Asian, admixed American and European) were identified using the five genetic principal components calculated using SPARK and 1000 Genomes Phase 3 populations75 and clustered using UMAP76. Principal components were calculated using linkage disequilibrium-pruned SNPs (r2=0.1, window size=1,000kb, step size=500 variants, after removing regions with complex linkage disequilibrium patterns) using GENESIS77, which accounts for relatedness between individuals, calculated using KING78.

Imputation was conducted using the Michigan Imputation Server79 with 1000 Genomes phase 3 version 5 as the reference panel49 (for AGRE and SSC), with the HRC r1.1 2016 reference panel80 (for AIMS-2-TRIALS) or using the TOPMed imputation panel81 (for both releases of SPARK). Details of imputation have been previously reported82. SNPs were excluded from polygenic risk scores if they had minor allele frequency <1%, had an imputation r2<0.4 or were multi-allelic.

We restricted our PGS associations to four GWAS. First, we included a GWAS of autism from the latest release from the iPSYCH cohort (iPSYCH-2015)83. This includes 19,870 autistic individuals (15,025 males and 4,845 females) and 39,078 individuals without an autism diagnosis (19,763 males and 19,315 females). All individuals included in this GWAS were born between May 1980 and December 2008 to mothers who were living in Denmark. GWAS was conducted on individuals of European ancestry, with the first ten genetic principal components included as covariates using logistic regression as provided in PLINK. Further details are provided elsewhere49. We additionally included GWAS for educational attainment (n=766,345, excluding the 23andMe dataset)35, intelligence (n=269,867)34, ADHD (n=20,183 individuals diagnosed with ADHD and 35,191 controls)36 and schizophrenia (69,369 individuals diagnosed with schizophrenia and 236,642 controls)37. These GWAS were selected given the relatively large sample size and modest genetic correlation with autism. Additionally, as a negative control, we included PGS generated from a GWAS of hair color (blonde versus other, n=43,319 blondes and n=342,284 others) from the UK Biobank, which was downloaded from https://atlas.ctglab.nl/traitDB/3495. This phenotype has SNP heritability comparable to that of the other GWAS used (h2=0.15, s.e.=0.014), is unlikely to be genetically or phenotypically correlated with autism and related traits, and has a sample size large enough to be a reasonably well-powered negative control.

PGS were generated for three phenotypes using polygenic risk scoring with continuous shrinkage (PRS-CS)84, which is among the best-performing polygenic scoring methods using summary statistics in terms of variance explained85. In addition, this method bypasses the step of identifying a P-value threshold. We set the global shrinkage prior () to 0.01, as is recommended for highly polygenic traits. Details of the SNPs included are provided in Supplementary Table 3.

De novo variants were obtained from Antaki et al.19. De novo variants (structural variants and SNVs) were called for all SSC samples and a subset of the SPARK samples (phase 1 genotype release, SNVs only). To identify high-impact de novo SNVs, we restricted data to variants with a known effect on protein. These are damaging variants: transcript_ablation, splice_acceptor_variant, splice_donor_variant, stop_gained, frameshift_variant, stop_loss, start_loss or missense variants with MPC86 scores >2. We further restricted data to variants in constrained genes with a LOEUF score <0.37 (ref. 87), which represent the topmost decile of constrained genes. For SVs, we restricted data to SVs affecting the most constrained genes, that is, those with LOEUF score <0.37, representing the first decile of most constrained genes. We did not make a distinction between deletions or duplications. To identify carriers, non-carriers and parents, we restricted our data to samples from the SPARK and SSC studies that had been exome sequenced and families in which both parents and the autistic proband(s) passed the genotyping QC.

For genes associated with severe developmental disorders, we obtained the list of constrained genes that are significant genes associated with severe developmental disorders from Kaplanis et al.27. To investigate the association of this set of genes with autism and developmental disorders, we first identified autistic carriers with a high-impact de novo variant and then divided this group into carriers who had at least one high-impact de novo variant in a DD gene and carriers with high-impact de novo variants in other constrained genes.

Only individuals with undiagnosed developmental disorders are recruited into the Deciphering Developmental Disorders study, and, as such, known genes associated with developmental disorders that are easy for clinicians to recognize and diagnose may be omitted from the genes identified by Kaplanis et al.27. To account for this bias, we ran sensitivity analyses using a larger but overlapping list of genes identified from the Developmental Disorder Gene-to-Phenotype database (DDG2P). From this database, we used constrained genes that are either confirmed or probable developmental disorder genes and genes for which heterozygous variants lead to developmental phenotypes (that is, mono-allelic or X-linked dominant).

We identified 19 autism core and associated features that (1) are widely used in studies related to autism; (2) are a combination of parent-, self- and other-reported and performance-based measures to investigate if reporter status affects the PGS association; (3) are collected in all three cohorts; and (4) cover a range of core and associated features in autism. The core features are

ADOS88: social affect

ADOS88: restricted and repetitive behavior domain total score

ADI89: communication (verbal) domain total score

ADI89: restricted and repetitive behavior domain total score

ADI89: social domain total score

RBS28

Parent-reported Social Responsiveness Scale-2 (ref. 90): total raw scores

SCQ29

Insistence of sameness factor (F1)

Social interaction factor (F2)

Sensorymotor behavior factor (F3)

Self-injurious behavior factor (F4)

Idiosyncratic repetitive speech and behavior (F5)

Communication skills factor (F6).

The associated features are

Vineland Adaptive Behavior Scales91: composite standard scores

Full-scale IQ

Verbal IQ

Nonverbal IQ

Developmental Coordination Disorders Questionnaire92.

Measures of IQ were quantified using multiple methods across the range of IQ scores in the AGRE, SSC and LEAP studies. In the SPARK study, IQ scores were available based on parent reports on ten IQ score bins (Fig. 1c). We used these as full-scale scores. For analyses involving the SPARK and SSC cohorts, we converted full-scale scores from the SSC into IQ bins to match what was available from the SPARK study and treated them as continuous variables based on examination of the frequency histogram (Supplementary Fig. 8). For the six factors, we excluded individuals who were minimally verbal (Factor analyses), but these individuals were not excluded for analyses with other autism features.

We identified seven questions relating to developmental delay in the SPARK medical screening questionnaire. These are all binary questions (yes or no). Summed scores ranged from 0 to 7. The developmental phenotypes include the presence of

ID, cognitive impairment, global developmental delay or borderline intellectual functioning

Language delay or language disorder

Learning disability (learning disorder, including reading, written expression or math; or nonverbal learning disability)

Motor delay (for example, delay in walking) or developmental coordination disorder

Mutism

Social (pragmatic) communication disorder (as included in DSM IV TR and earlier)

Speech articulation problems.

We included the age of first words and the age of walking independently for further analyses. This was recorded using parent-reported questionnaires in the SPARK study and in ADI-R89 in the SSC study. While other developmental phenotypes are available, we focused on these two, as they represent major milestones in motor and language development and are relatively well characterized.

Before any statistical analyses, we visually inspected the distributions of the variables. All continuous variables were approximately normally distributed with the exception of the age of first words, the age of walking independently and the count of co-occurring developmental disabilities. For these three variables, we used quasi-Poisson or negative binomial regression to account for overdispersion in the data and because the variance was much greater than the mean. These models produced the same estimate but modestly different standard errors. Both have two parameters. However, while quasi-Poisson regression models the variance as a linear function of the mean, the negative binomial models the variance as a quadratic function of the mean. The model that produced the lower residual deviance was chosen between the two. For all other continuous variables, we used linear regression and parametric tests. For binary data, we used logistic regression as there was not a large imbalance in the case:control ratio.

For each cohort, PGS and high-impact de novo variants were regressed against the autism features with sex and the first ten genetic principal components as covariates in all analyses, with all continuous independent variables standardized. In addition, array was included as a covariate in SSC and AGRE datasets. This was performed using linear regression for standardized quantitative phenotypes, logistic regression for binary phenotypes (for example, association between PGS and the presence of a high-impact de novo variant), Poisson regression for count data (number of developmental disorders or delays, not standardized) and negative binomial regression for the age of walking independently or the age of first words (not standardized; MASS93 package in R).

For the association between genetic variables and core and associated autism phenotypes, we first conducted linear regression analyses for the four PGS first using multivariate regression analyses with data from SPARK (waves 1 and 2), SSC, AGRE and AIMS-2-TRIALS LEAP. This is of the form:

$$yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{textrm{intelligence}} + {textrm{sex}} + {textrm{age}} + 10 {textrm{PCs}},$$

(1)

where EA is educational attainment and 10PCs are ten principal components. For the negative control, we added the negative control as an additional independent variable in equation (1):

$$begin{array}{lll}yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{textrm{intelligence}} \+ {textrm{PGS}}_{textrm{hair color}} + {textrm{sex}} + {textrm{age}} + 10{textrm{PCs}}.end{array}$$

(2)

For the AGRE and SPARK studies, we ran equivalent mixed-effects models with family ID modeled as random intercepts to account for relatedness between individuals. This was carried out using the lme4 (ref. 94) package in R.

For high-impact de novo variants, we included the count of high-impact de novo variants as an additional independent variable in equation (1) and ran regression analyses for SPARK (wave 1 only) and SSC. To ensure interpretability across analyses, we retained only individuals who passed the genotypic QC, which included only individuals of European ancestries. Family ID was included as a random intercept:

$$begin{array}{l}yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{{mathop{{{rm{intelligence}}}}} } \+ {textrm{high-impact de novo count}} + {textrm{sex}} + {textrm{age}} + 10{textrm{PCs}.}end{array}$$

(3)

Effect sizes were meta-analyzed across the three cohorts using inverse-variance-weighted meta-analyses with the following formula:

$$begin{array}{l} {w_{i}} = {{mathrm{SE}}_{i}^{-2}} \ {{mathrm{SE}}_{mathrm{meta}}} = {surd}left(left({Sigma}_{1} w_{i}right)^{-1}right)\ {{beta}_{mathrm{meta}} = {Sigma}_{i}{{beta}_{i}}{{w}_{i}}{left({{Sigma}_{i}}{{w}_{i}}right)}^{-1}},end{array}$$

(4)

where i is the standardized regression coefficient of the PGS, SEi is the associated standard error and wi is the weight. P values were calculated from Z scores. Given the high correlation between the autism features and phenotypes, we used BenjaminiYekutieli false discovery rates to correct for multiple testing (corrected P<0.05). We calculated heterogeneity statistics (Cochrans Q and I2 values) for the PGS meta-analyses but not for the associations with high-impact de novo variants, as the latter were calculated using only two datasets (SSC and SPARK).

For the SPARK and SSC studies, we investigated the association between PGS (equation (1)) and being a carrier of a high-impact de novo variant (equation (3)) and the age of first walking and first words using negative binomial regression and conducted inverse-variance meta-analyses (equation (4)). We ran the same analyses for the SPARK study to investigate the association between PGS (equation (1)) and high-impact de novo variants (equation (3)) and counts of co-occurring developmental disabilities (quasi-Poisson regression). Leave-one-out analyses were conducted by systematically excluding one of seven co-occurring developmental disabilities and reconducting the analyses.

To investigate additivity between common and high-impact de novo variants, we conducted logistic regression with carrier status as a dependent binary variable and all PGS included as independent variables and genetic principal components, sex and age included as covariates. This was carried out separately for SPARK (wave 1) and SSC and meta-analyzed as outlined earlier.

Statistical significance of differences in factor scores between sexes were computed using t-tests. Associations with age and IQ bins were conducted using linear regressions after including sex as a covariate.

Matrix equivalency tests were conducted using the Jennrich test in the psych66 package in R. Power calculations were conducted using simulations. Statistical differences between pairwise correlation coefficients (carriers versus non-carriers) in core and associated features were tested using the package cocor95 in R. Using scaled existing data on full-scale IQ, adaptive behavior and motor coordination, we generated correlated simulated variables at a range of correlation coefficients to reflect the correlation between the six core factors and the three associated features. We then ran regression analyses using the simulated variable and high-impact de novo variants as provided in equation (3). We repeated this 1,000 times and counted the fraction of outcomes for which the association between high-impact de novo variant count and the simulated variable had P<0.05 to obtain statistical power. Differences in the age of walking and the age of first words between groups of autistic individuals and siblings were calculated using Wilcoxon rank-sum tests.

Polygenic transmission deviation was conducted using polygenic transmission disequilibrium tests14. To allow comparisons with midparental scores, residuals of the autism PGS were obtained after regressing out the first ten genetic principal components. These residuals were standardized by using the parental mean and standard deviations. We obtained similar results using PGS that had not been residualized for the first ten genetic principal components. We defined individuals without co-occurring ID as individuals whose full-scale IQ is above 70 the SSC and SPARK studies. Additionally, in the SPARK cohort, we excluded any of these participants who had a co-occurring diagnosis of intellectual disability, cognitive impairment, global developmental delay or borderline intellectual functioning. Analyses were conducted separately in the SSC and SPARK cohorts and meta-analyzed using inverse-variance-weighted meta-analyses. We additionally conducted pTDT analyses on non-autistic siblings to investigate differences between males and females.

For sex differences in high-impact de novo variants, we calculated relative risk in autistic females versus males based on (1) all carriers, (2) carriers of DD genes and (3) carriers of non-DD genes (SPARK wave 1 and SSC). For sensitivity analyses, we conducted logistic regression with sex as the dependent variable and carrier status for DD genes and either full-scale IQ and motor coordination scores (in SPARK wave 1 and SSC) or number of developmental disorders (only in SPARK wave 1) as covariates. For each sensitivity analysis, we provide the estimates of the unconditional analysis as well (that is, without the covariates).

We opted to conduct heritability analyses using unscreened population controls rather than family controls (that is, pseudocontrols or unaffected family members), as this likely reduces SNP heritability96 owing to parents having higher genetic likelihood for autism compared to unselected population controls55 and due to assortative mating97. Casecontrol heritability analyses were conducted using the ABCD cohort as population controls; specifically, the ABCD child cohort in the USA, recruited at the age of 9 or 10 years. This cohort is reasonably representative of the US population in terms of demographics and ancestry. As such, it represents an excellent comparison cohort for the SPARK and SSC cohorts. The ABCD cohort was genotyped using the Smokescreen genotype array, a bespoke array designed for the study containing over 300,000 SNPs. Genetic QC was conducted identically as for SPARK. Genetically homogeneous groups were identified using the first five genetic principal components followed by UMAP clustering with the 1000 Genomes data. We restricted our analyses to 4,481 individuals of non-Finnish European ancestries in the ABCD cohort. Scripts for this are available at https://github.com/vwarrier/ABCD_geneticQC. Imputation was conducted, similar to the analysis of SPARK data, using the TOPMed imputation panel.

For casecontrol heritability analyses, we combined genotype data from the ABCD cohort and from autistic individuals from the SPARK and SSC cohorts. We restricted the analysis to 6,328,651 well-imputed SNPs (r2>0.9) with minor allele frequency >1% in all datasets. Furthermore, we excluded multi-allelic SNPs and SNPs with minor allele frequency difference of >5% between the three datasets and, in the combined dataset, were not in HardyWeinberg equilibrium (P>1106) or had genotyping rate <99%. We additionally excluded related individuals, identified using GCTA-GREML, and individuals with genotyping rate <95%. We calculated genetic principal components for the combined dataset using 52,007 SNPs with minimal linkage disequilibrium (r2=0.1, 1,000kb, step size of 500 variants, removing regions with complex long-range linkage disequilibrium). Visual inspection of the principal-component plots did not identify any outliers (Supplementary Fig. 9). While our QC procedure is stringent, we note that there will be unaccounted-for effects in SNP heritability due to fine-scale population stratification, differences in genotyping array and participation bias in the autism cohorts. However, our focus is on the differences in SNP heritability between subgroups of autistic individuals, and unaccounted-for casecontrol differences will not affect this.

We calculated SNP heritability for autism and additionally in subgroups stratified for the presence of ID, sex, sex and ID together, and the presence of high-impact de novo variants. We also conducted SNP heritability in subgroups of autistic individuals with scores >1s.d. from the mean for each of the six factors, autistic individuals with F1 scores>F2 scores and autistic individuals with F2 scores>F1 scores.

We calculated the observed-scale SNP heritability (baseline and subgroups) using GCTA-GREML52,53 and, additionally, using PCGC54. In all models except for the sex-stratified models, we included sex, age in months and the first ten genetic principal components as covariates. In the sex-stratified models, we included age in months and the first ten genetic principal components as covariates. For sex-stratified heritability analyses, both case and control data were from the same sex. For GCTA-GREML, the observed-scale SNP heritability was converted into liability-scale SNP heritability using equation (23) from Lee et al.98. PCGC estimates SNP heritability directly on the liability scale using the prevalence rates from Maenner et al.99. For all analyses, we ensured that the number of cases did not exceed the number of controls, with a maximum case:control ratio of 1.

We used prevalence rates from Maenner et al.99, which provides prevalence of autism among 8 year olds (1.8%). The study also provides prevalence rates by sex and by the presence of ID. However, there is wide variation in autism prevalence. We thus recalculated the SNP heritability across a range of state-specific prevalence estimates obtained from Maenner et al.99. For estimates of liability-scale heritability for subtypes defined by factor scores >1s.d. from the mean, we estimated a prevalence of 16% of the total prevalence. For F1>F2 and F2>F1, prevalence was estimated at 50% of the total autism prevalence. Estimating approximate population prevalence of autistic individuals with high-impact de novo variant carriers is difficult due to ascertainment bias in existing autism cohorts. However, a previous study has demonstrated that the mutation rate for rare protein-truncating variants is similar between autistic individuals and siblings from the SSC and autistic individuals and population controls from the iPSYCH sample in Denmark, which does not have a participation bias100, implying that the de novo mutation rate in autistic individuals from the SPARK and SSC cohorts may be generalizable. Using the sex-specific proportion of de novo variant carriers and autism prevalence, we calculated a prevalence of 0.2% for being an autistic carrier of a high-impact de novo variant.

For sex-stratified SNP heritability analyses, we additionally calculated SNP heritability for a range of state-specific prevalence estimates to better model state-specific factors that contribute to autism diagnosis. In addition, using a total prevalence of 1.8%, we estimated SNP heritability using a male:female ratio of 3.3:1 (ref. 51) to account for diagnostic bias that may inflate the ratio.

We used GCTA-GREML to also estimate SNP heritability for the six factors, full-scale IQ and the bivariate genetic correlation between them. We used the same set of SNPs used in the casecontrol analyses. We were unable to conduct bivariate genetic correlation for the casecontrol datasets due to limitations of sample size.

We received ethical approval to access and analyze de-identified genetic and phenotypic data from the three cohorts from the University of Cambridge Human Biology Research Ethics Committee.

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

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Genetic correlates of phenotypic heterogeneity in autism - Nature.com

Recommendation and review posted by Bethany Smith

Among neurologic complaints, migraines are the most common cause of productivity loss and emergency room visits. Migraines may be the most painful type of headache, increasing stroke, and heart attack risk in men.

While migraines tend to affect more women, migraines in men do happen. About 9% of men are regular sufferers (vs. 17% of women), and certain types of headaches like cluster headaches are more common in men. Genetics also play a role since approximately 70% of sufferers have a close relative with the problem.

Today, some consider chronic migraine (>15 migraine days per month) as an individual and societal burden as it is more disabling than episodic migraine. A hypothesis to this higher probability of progression could be that men are often not diagnosed or misdiagnosed. The theory may be that they are less likely to report or seek medical treatment for migraines.

It is a false notion that migraine is a women's disease- This stigmatizes the disorder and denies men access to proper care. It is important to be aware of these statistics and seek help if you suffer with migraines. Read on to find out moreand to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID.

A few years ago, scientists started looking at the influence of female hormones in men with migraine. This study reports that men with migraine displayed an increased level of estradiol (type of estrogen hormone) and clinical evidence of androgen deficiency (less male hormones). If you are having more than 15 headaches a month that are debilitating and interfere with your daily functioninga visit is warranted to your physician. Once the initial workup is normal, they can refer you to a migraine specialist once conservative measures fail. Looking at medications, supplements and your daily triggers will help you reduce pain and frequency of attacks. There are daily medications and well as preventive prescription medications that can control the overactivity of migraine attacks.

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Sleep cycle regulation is very important, go to bed at the same time every day, including on weekends and holidays. The brain's pathways responsible for sleep if disrupted can contribute to migraines.

It is important to seek out complementary medicine that is proven effective in migraines:

Apply lavender oil or peppermint to the base of your neck or use aromatherapy. Inhaling lavender essential oil may ease migraine pain.

Acupuncture can help to mitigate pain and the severity of attacks in many patients.

Ginger prevents nausea that can occur in many migraine patients.

Yoga and biofeedback help many patients cope with pain along with complimentary as well as medication management.

There are many migraine-specific vitamins that your migraine neurologist can recommend along with treatment.

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Avoid certain foods. Diet plays a vital role in preventing migraine attacks. Your diet plays a part, too. In about 10% of people with these headaches, food is a trigger. Choose better food. Eat as much wholesome, fresh food, like fruits and vegetables, as you can. Avoid processed and packaged foods.

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Tyramine is a natural compound that forms in protein-rich foods as they age. It's also a trigger for migraines. These cheeses are high in tyramine:

Chemicals added to food to enhance their flavor or help them stay fresh longer may bring on a headache:

Limit stress as tension's a common trigger. Using mediation, music, meditation, yoga, and massage to relieve tension can help. There are many evidence-based complementary techniques. Along with your prescribed treatment, you might want to try one of these to help prevent migraines, such as acupuncture, massage & cognitive behavioral therapy

It is wise to avoid a drop in blood sugar which can set off a migraine. My patients know to drink at least 4-5 glasses of water to avoid dehydration, which can trigger headaches.

Exercise regularly, many of my patients are afraid it might trigger a migraine. Overdoing a workout may trigger a headache for some people, but research suggests regular, moderate aerobic exercise may make migraines shorter, less severe, and happen less often for many people. Vigorous exercise might be a trigger in migraineurs, but overall the benefits of physical activity far outweigh the risk for people with migraine.

Regular exercise is associated with a reduction in the frequency and intensity of migraines, says. Avoid exercise if you're in the middle of a migraine attack, as it can make the pain worse. When you're exercising it can help keep future away attacks by relieving stress, a common migraine trigger.

Exercise also stimulates the release of feel-good hormones called endorphins and enkephalins which are our natural painkillers and natural antidepressants. Migraines share brain receptors with serotonin responsible for our mood.

Preventive or good habits can go a long way to prevent migraines. Yet, it is not a substitute for a proper evaluation by a migraine neurologist. Good sources of information are the American Headache Society (AHS) and the American Migraine Foundation (AMF). The most important thing I keep in mind when treating my patients is that everyone is unique and the approach is never a one size fits all solution. Be aware of overusing over-the-counter pain relievers as they can actually trigger medication overuse headaches and cause stomach upset and ulcers. There is hope for your pain and you do not have to suffer in silence. And to protect your life and the lives of others, don't visit any of these 35 Places You're Most Likely to Catch COVID.

Shae Datta, MD, co-director, NYU Langone's Concussion Center, and director of cognitive neurology at NYU Langone HospitalLong Island.

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Best Habits to Prevent a Migraine, Says Neurologist Eat This Not That - Eat This, Not That

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Research News

The subfossil jawbone of a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. A genomic study includes an analysis of DNA extracted from a tooth attached to this jawbone, which is now housed at the Natural History Museum at the University of Oslo. Photo: Karsten Sund, Natural History Museum, University of Oslo

By CHARLOTTE HSU

A new study is providing an enhanced look at the intertwined evolutionary histories of polar bears and brown bears.

Becoming separate species did not completely stop these animals from mating with each other. Scientists have known this for some time, but the new research draws on an expanded data set including DNA from an ancient polar bear tooth to tease out more detail.

The story that emerges reveals complexities similar to those that complicate human evolutionary history.

The formation and maintenance of species can be a messy process, says Charlotte Lindqvist, associate professor of biological sciences, College of Arts and Sciences, and an expert on bear genetics. Whats happened with polar bears and brown bears is a neat analog to what were learning about human evolution: that the splitting of species can be incomplete.

As more and more ancient genomes have been recovered from ancient human populations, including Neanderthals and Denisovans, were seeing that there was multidirectional genetic mixing going on as different groups of archaic humans mated with ancestors of modern humans. Polar bears and brown bears are another system where you see this happening.

We find evidence for interbreeding between polar bears and brown bears that predates an ancient polar bear we studied, she says. And, moreover, our results demonstrate a complicated, intertwined evolutionary history among brown and polar bears, with the main direction of gene flow going into polar bears from brown bears. This inverts a hypothesis suggested by other researchers that gene flow has been unidirectional and going into brown bears around the peak of the last ice age.

A mother polar bear and her 2-year-old cubs in northwestern Greenland. Photo: ystein Wiig

The study was published June 6 in the Proceedings of the National Academy of Sciences. It was led by Lindqvist; Luis Herrera-Estrella at the National Laboratory of Genomics for Biodiversity (LANGEBIO) in Mexico and Texas Tech University; and Kalle Leppl at the University of Oulu in Finland. Tianying Lan, a former UB postdoctoral researcher now at Daicel Arbor Biosciences, was co-first author with Leppl.

The concept of Arctic-adapted polar bears capturing genetic material from brown bears, which are adapted to life in lower latitudes, is one of several findings of possible interest for scientists concerned with climate change impacts on threatened species.

As the world warms and Arctic sea ice declines, polar bears and brown bears may run into each other more frequently in places where their ranges overlap. This makes their shared evolutionary history a particularly intriguing subject of study, Lindqvist says.

An adult male polar bear in northwestern Greenland. Photo: ystein Wiig

Splitting of species can be messy process

As Lindqvist explains, scientists once thought modern humans and Neanderthals simply split into separate species after evolving from a common ancestor. Then, researchers found Neanderthal DNA in modern Eurasian people, implying that modern human populations received an influx of genes from Neanderthals at some point in their shared evolutionary history, she says.

Only later did scientists realize that this genetic intermingling also supplemented Neanderthal populations with modern human genes, Lindqvist adds. In other words, interbreeding can be complex, not necessarily a one-way street, she says.

The new study on bears reveals a remarkably similar story: The analysis finds evidence of hybridization in both polar bear and brown bear genomes, with polar bears in particular carrying a strong signature of an influx of DNA from brown bears, researchers say. Earlier research proposed the inverse pattern only, Lindqvist says.

Its exciting how DNA can help reveal ancient life history. Gene flow direction is harder to determine than merely its presence, but these patterns are vital to understanding how past adaptations have transferred among species to give modern animals their current features, says Leppl, postdoctoral researcher in the research unit of mathematical sciences at the University of Oulu.

Population genomics is an increasingly powerful toolbox to study plant and animal evolution, and the effects of human activity and climate change on endangered species, says Herrera-Estrella, Presidents Distinguished Professor of Plant Genomics and director of the Institute of Genomics for Crop Abiotic Stress Tolerance in the Texas Tech Department of Plant and Soil Science. He is also a professor emeritus at LANGEBIO. Bears dont provide simple speciation stories any more than human evolution has. This new genomic research suggests that mammalian species groups can hide complicated evolutionary histories.

The subfossil jawbone of a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. Photo: Karsten Sund, Natural History Museum, University of Oslo

Evidence from modern bear genomes and DNA from an ancient tooth

The study analyzed the genomes of 64 modern polar and brown bears, including several new genomes from Alaska, a state where both species are found.

The team also produced a new, more complete genome for a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. DNA for the ancient polar bear was extracted from a tooth attached to a subfossil jawbone, which is now housed at the Natural History Museum at the University of Oslo.

Using this data set, researchers estimate that polar bears and brown bears started to become distinct species about 1.3 to 1.6 million years ago, updating prior assessments made by some of the same scientists. The age of the split has been and remains a topic of scientific debate, with past interbreeding and limited fossil evidence for ancient polar bears among factors that make the timing hard to pinpoint, Lindqvist says.

In any case, after becoming their own species, polar bears endured dramatic population decline and a prolonged genetic bottleneck, leaving these bears with much less genetic diversity than brown bears, the new study concludes. The findings confirm past research pointing to the same trends, and add evidence in support of this hypothesis.

Genomes analyzed in a new study on bears include that of this bear, pictured here in 1995 on Alaska's North Slope. Scientists had wondered if this bear might be a brown bear-polar bear hybrid, but the new research finds that, This bear is not a hybrid, but simply a light-colored brown bear, says UB biologist Charlotte Lindqvist. Photo: Richard Shideler, Division of Wildlife Conservation, Alaska Department of Fish and Game

Together with the analysis of gene flow, these findings are providing new insights into the messy, intertwined evolutionary history of polar bears and brown bears.

The international research team included scientists from UB, LANGEBIO, Texas Tech, the University of Oulu, the Far Northwestern Institute of Art and Science, the Alaska Department of Fish and Game, the Natural History Museum at the University of Oslo, Nanyang Technological University, University of Helsinki and Aarhus University.

The research was funded by the National Fish and Wildlife Foundation, U.S. National Science Foundation, Alaska Department of Fish and Game, and U.S. Geological Survey.

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Study offers better look at tangled evolutionary histories of polar bears, brown bears - UB Now: News and views for UB faculty and staff - University...

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