Mapping study yields novel insights into DNA-protein connection, paving way for researchers to target new treatments

A new genetic mapping study led by researchers at the Johns Hopkins Bloomberg School of Public Health traces links between DNA variations and thousands of blood proteins in two large and distinct populations. The results should help researchers better understand the molecular causes of diseases and identify proteins that could be targeted to treat these diseases.
The study included more than 9,000 Americans of European or African ancestry, and generated maps of DNA-to-protein links for both groups. The study is thought to be the first of its kind to include two large and ancestrally distinct population cohorts. Proteins play a critical role in cellular function, and changes in protein mechanisms — often regulated by DNA variations — can lead to disease. DNA-to-protein mapping could help explain differences in the rates of some diseases in the two groups and help researchers understand some health disparities.
The study appears May 2 in Nature Genetics.
Researchers have been mapping the molecular roots of human diseases for decades through so-called genetic mapping studies. The best known is the genome-wide association study (GWAS). A GWAS typically links variations in DNA to disease risk by analyzing the DNA of subjects — often tens or hundreds of thousands of individuals at a time — along with their history of a given disease. This uncovers statistical associations linking the disease to specific DNA variations.
Missing from the GWAS picture: Most of the disease-linked DNA variants identified by GWAS analysis do not lie within protein-coding genes. Researchers therefore assumed that many — even most — disease-linked DNA variants affect proteins indirectly, by regulating one or more steps in the gene-to-protein production process, thereby altering protein levels. Linking diseases directly to proteins, researchers can better understand the roots of disease — and also identify protein targets for disease prevention and treatments.
“This relatively new kind of mapping study provides a wealth of information that will allow researchers to test for potential links of proteins on various types of health outcomes — risk of cancers, heart disease, severe COVID — and help to develop or repurpose therapeutic drugs,” says study senior author Nilanjan Chatterjee, PhD, Bloomberg Distinguished Professor in the Department of Biostatistics at the Bloomberg School.

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Nanotechnology enables visualization of RNA structures at near-atomic resolution

We live in a world made and run by RNA, the equally important sibling of the genetic molecule DNA. In fact, evolutionary biologists hypothesize that RNA existed and self-replicated even before the appearance of DNA and the proteins encoded by it. Fast forward to modern day humans: science has revealed that less than 3% of the human genome is transcribed into messenger RNA (mRNA) molecules that in turn are translated into proteins. In contrast, 82% of it is transcribed into RNA molecules with other functions many of which still remain enigmatic.
To understand what an individual RNA molecule does, its 3D structure needs to be deciphered at the level of its constituent atoms and molecular bonds. Researchers have routinely studied DNA and protein molecules by turning them into regularly packed crystals that can be examined with an X-ray beam (X-ray crystallography) or radio waves (nuclear magnetic resonance). However, these techniques cannot be applied to RNA molecules with nearly the same effectiveness because their molecular composition and structural flexibility prevent them from easily forming crystals.
Now, a research collaboration led by Wyss Core Faculty member Peng Yin, Ph.D. at the Wyss Institute for Biologically Inspired Engineering at Harvard University, and Maofu Liao, Ph.D. at Harvard Medical School (HMS), has reported a fundamentally new approach to the structural investigation of RNA molecules. ROCK, as it is called, uses an RNA nanotechnological technique that allows it to assemble multiple identical RNA molecules into a highly organized structure, which significantly reduces the flexibility of individual RNA molecules and multiplies their molecular weight. Applied to well-known model RNAs with different sizes and functions as benchmarks, the team showed that their method enables the structural analysis of the contained RNA subunits with a technique known as cryo-electron microscopy (cryo-EM). Their advance is reported in Nature Methods.
“ROCK is breaking the current limits of RNA structural investigations and enables 3D structures of RNA molecules to be unlocked that are difficult or impossible to access with existing methods, and at near-atomic resolution,” said Yin, who together with Liao led the study. “We expect this advance to invigorate many areas of fundamental research and drug development, including the burgeoning field of RNA therapeutics.” Yin also is a leader of the Wyss Institute’s Molecular Robotics Initiative and Professor in the Department of Systems Biology at HMS.
Gaining control over RNA
Yin’s team at the Wyss Institute has pioneered various approaches that enable DNA and RNA molecules to self-assemble into large structures based on different principles and requirements, including DNA bricks and DNA origami. They hypothesized that such strategies could also be used to assemble naturally occurring RNA molecules into highly ordered circular complexes in which their freedom to flex and move is highly restricted by specifically linking them together. Many RNAs fold in complex yet predictable ways, with small segments base-pairing with each other. The result often is a stabilized “core” and “stem-loops” bulging out into the periphery.

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AI-enabled ECGs may identify patients at greater risk of stroke, cognitive decline

Atrial fibrillation, the most common cardiac rhythm abnormality, has been linked to one-third of ischemic strokes, the most common type of stroke. But atrial fibrillation is underdiagnosed, partly because many patients are asymptomatic.
Artificial intelligence-enabled electrocardiography (ECG) was recently shown to identify the presence of brief episodes of atrial fibrillation, and the ability of an AI-enabled ECG algorithm to predict atrial fibrillation up to 10 years before clinical diagnosis has been confirmed in a population-based study conducted by Mayo Clinic researchers.
A new population-based study from Mayo Clinic now offers evidence that the algorithm can help identify patients at greater risk of cognitive decline. AI-enabled ECG that shows high probability of atrial fibrillation also was associated with the presence of infarctions, or incidents of cerebral stroke, on MRI, according to the study.
The study is described in an article, “Artificial Intelligence-Enabled Electrocardiogram for Atrial Fibrillation Identifies Cognitive Decline Risk and Cerebral Infarcts,” which is published in Mayo Clinic Proceedings.
Most of the infarctions observed were subcortical, meaning that they occurred in the region of the brain below the cortex. This suggests that AI-enabled ECG not only predicts atrial fibrillation, but also detects other cardiac disease markers and correlates with small vessel cerebrovascular disease and cognitive decline.
“This study finds that artificial intelligence-enabled electrocardiography acquired during normal sinus rhythm was associated with worse baseline cognition and gradual decline in global cognition and attention,” says Jonathan Graff-Radford, M.D., a Mayo Clinic neurologist and the study’s corresponding author. “The findings raise the question whether initiation of anticoagulation is an effective and safe preventive strategy in individuals with a high AI-ECG algorithm score for reducing the risk of stroke and cognitive decline.”
Prospective controlled studies are needed to determine whether a high atrial fibrillation score on an AI-enabled electrocardiogram could be a biomarker to identify patients for anticoagulation or more aggressive stroke risk factor modification, Dr. Graff-Radford says.
The retrospective study reviewed sinus-rhythm ECG of 3,729 patients with a median age of 74 years who were enrolled in the Mayo Clinic Study of Aging between 2004 and 2020. Adjusting for demographic factors, the AI-enabled ECG atrial fibrillation score correlated with lower baseline and faster decline in global cognitive scores. About one-third of the patients who underwent ECG also had an MRI, and high atrial fibrillation probability in the ECG correlated with MRI-detected cerebral infarcts.
“Application of this AI-ECG algorithm may be another way to screen individuals not only to determine risk of atrial fibrillation, but also to identify future risk of cognitive decline and stroke,” says Dr. Graff-Radford.
Research reported in the article was supported by grants from the National Institute on Aging and the National Institutes of Health. The study was made possible by the Rochester Epidemiology Project. Potential competing interests are identified in the article. Among the potential competing interests, Peter Noseworthy, M.D., a Mayo Clinic cardiologist, and Mayo Clinic have filed patents related to the application of AI to ECG for diagnosis and risk stratification.
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Materials provided by Mayo Clinic. Original written by Jay Furst. Note: Content may be edited for style and length.

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Ablation therapy applied to stomach disorders

Researchers from the Auckland Bioengineering Institute have shown that ablation therapy, often used to correct an abnormally beating heart, could be used to correct disorders of the stomach.
In normal circumstances the stomach is coordinated by underlying bioelectrical “slow wave” activity, which coordinates the contraction of the muscles that mix and move contents into and through the gastrointestinal (GI) tract. When these electrical slow waves don’t work as they should, described as ‘stomach dysrhythmias’, it can lead to severe GI disorders and symptoms of nausea, vomiting, pain and bloating, and is often untreatable.
When dysrhythmic activity occurs in the heart it results in irregular heartbeat, a condition called atrial fibrillation, which is often treated with ablation therapy, which involves the precise ‘burning’ of tissue to control the naturally occurring electricity in the heart. Dr Tim Angeli-Gordon and PhD student Zahra Aghababaie of the ABI have shown, in research that featured as the cover story on latest issue of the American Journal of Physiology, the technique could also be applied to control the naturally occurring bioelectrical “slow wave” activity in the stomach.
Last year the team published the initial results of their research using ablation in the stomach, demonstrating that it was possible to use the technique to block the electrical activation of the stomach in localised regions. “The more recent paper builds on that foundational work and is an important advance because we have now shown that we can eliminate abnormal electrical activation with ablation, and also that the normal electrical activation of the stomach can be restored after ablation,” says Dr Angeli-Gordon. “Although these studies were done in our pre-clinical lab, they demonstrate the powerful potential of ablation in the stomach which may now be able to be translated as a therapy for patients suffering from gastrointestinal disorders.”
Unusually, the research was illustrated on the cover of the journal by co-author of the paper, Zahra Aghababaie, who created the artwork from some of her histology (microscopic) images of the gastrointestinal system, which she captioned as “the Enchanted Forest of the gut-brain.” “Within the human stomach, a great wild and vivid ‘forest’ exists working in harmony through sequences of organised contractions to extract the essential source of energy,” she writes. “The coordination of this wonderful machinery is only possible thanks to an assembly of dedicated cells orchestrating the ballet of digestion. However, sometimes the harmony of this delicate system is disturbed with abnormal dysrhythmic activity.”
Zahra’s artwork was initially created as a submission to the Art of BioEng, a competition that the ABI had held since 2015 to encourage the Institute’s bioengineers to capture, through art, the world that new technologies have allowed us to see what is often beyond our imagination. “Biology imaging is both beautiful and enchanting,” she says. “We are working in a cross-disciplinary field at the ABI — engineering, biology, physics and so on. I think art can give us a moment of peace, a moment to stop, observe and appreciate. And perhaps remind us to do this more often in our everyday life and work, and in our case, our research.”
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Cilia-free stem cells offer new path to study rare diseases

A group of rare diseases called ciliopathies — polycystic kidney disease notable among them — emerge from defects in cilia. These are the tiny hairlike structures on the surface of almost every cell type. The specific molecular-level disruptions in cilia that trigger these diseases are poorly understood.
In a novel experiment, scientists “knocked out,” or deleted, the cilia in a population of otherwise normal human pluripotent stem cells. Subsequently, human tissues and mini-organ structures (organoids) derived from these cilia-free stem cells manifested ciliopathy-like symptoms.
The journal Nature Biomedical Engineering published the findings April 27.
“We are trying to understand what cilia do, so we ablated them from these cells,” said Benjamin Freedman, whose lab at UW Medicine led the work. “We wanted to see if the cells would re-create symptoms of ciliopathy without the cilia. Sure enough, when we turned the cells into tissues and organoids (tissue-like structures), they re-created polycystic kidney disease and problems with brain development.”
The cilia-knockout stem cells “represent a powerful new tool for understanding this group of diseases, which can be used to guide therapy development,” said Freedman, an associate professor of medicine, Division of Nephrology at the University of Washington School of Medicine in Seattle.
He described cilia as cellular compartments where important proteins are brought together, as if in a Zoom meeting, to make decisions that guide a cell’s development. Without the meeting room, these proteins can’t talk to each other and cell-development decisions are not made.
There are at least 15 ciliopathies, each rare in terms of population prevalence and each with its own constellation of partially overlapping symptoms. Ciliopathies frequently present at birth; an exception is polycystic kidney disease (PKD), which affects about 1 in 500 people and causes clinical problems mostly later in life.
Because ciliopathies affect many organs, pluripotent stem cells, which can turn into any tissue in the body, could offer a “one-stop shop” to study these diseases.
In removing cilia from human pluripotent stem cells, Freedman and his colleagues sought to understand what would happen in their subsequent transformation into tissues and organoids. As it happened, the cilia-free stem cells appeared normal but were unable to fully realize new forms.
“It was surprising to me that, at a certain point after they were turning into tissues, they seemed to break down,” Freedman said. “They struggled to transform into anything sophisticated. I think one lesson from this is that the cilia help get cells through their final stage of development.”
It was first reported in 2000 that PKD could stem from defects in cilia, but the mechanism of damage that causes cysts to form has escaped scientists. By creating cilia-free stem cells that harbor disease, Freedman said, the researchers now have a framework with which to test and compare molecular actions in the cilia.
“By comparing cells that totally lack cilia to cells that possess cilia but lack PKD genes, as well as to normal cells, we have the whole range of cell types that should enable us to deduce what’s going on among the molecules involved. For almost 30 years we’ve known the genes involved in PKD — even before we knew that cilia were implicated. Hopefully having these distinct cell types will enable us to figure out what specific disruption these genetic molecules are causing to create PKD.”

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New research could help identify babies at risk of brain bleeds

Researchers from WEHI (the Walter and Eliza Hall Institute) have uncovered a new way to help identify babies and foetuses at high-risk of developing brain bleeds, paving the way for better early intervention.
Brain bleeds in unborn babies and newborns can lead to stroke and permanent neurological conditions, such as cerebral palsy.
While brain bleeds can sometimes be treated with platelet transfusions, the invasive procedures can be dangerous, and it had been unclear which babies would benefit most.
At a glance Research finds a new way to help identify unborn and newborn babies at risk of brain bleeds. Preclinical studies show brain bleeds will occur if platelet levels drop to 10 per cent or below in foetuses and newborns. The new threshold could be used to determine which babies should have treatment, transforming platelet transfusion practises and avoiding unnecessary procedures.WEHI researchers Dr Alison Farley and Dr Samir Taoudi are investigating how levels of platelets, small blood cells best known for enabling blood clots, affect brain bleeds to better understand when platelet transfusion should be deployed.
A new analysis of preclinical models has found brain bleeds always occurred when platelet levels dropped to 10 per cent or below in newborns and foetuses.

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Sensor makes strides in detecting infection indicators

University of Texas at Dallas bioengineers in collaboration with EnLiSense LLC have designed a wearable sensor that can detect two key biomarkers of infection in human sweat, a significant step toward making it possible for users to receive early warnings of infections such as COVID-19 and influenza.
The Erik Jonsson School of Engineering and Computer Science researchers’ study, published online March 3 in Advanced Materials Technologies, demonstrates that the sweat sensor can identify the biomarkers interferon-gamma-inducible protein (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Elevated levels of IP-10 and TRAIL indicate what is known as a cytokine storm, a surge of pro-inflammatory immune proteins generated in the most serious infections.
“Our work is pioneering since, until this date, it was unclear whether these molecules were present in sweat,” said Dr. Shalini Prasad, head of bioengineering and the Cecil H. and Ida Green Professor in Systems Biology Science. “We established that our low-volume passive sweat technology is indeed able to measure these biomarkers.”
The ability to detect IP-10 and TRAIL is important because, in addition to C-reactive protein (CRP), they allow diagnosticians to distinguish between viral and bacterial infections. The research builds on a study that Prasad’s team presented at the April 2021 meeting of the American Chemical Society that demonstrated that the sweat sensor could detect CRP to indicate an impending cytokine storm. A molecular test, such as a polymerase chain reaction (PCR) test, would still be needed to confirm the type of pathogen causing an infection, Prasad said.
“We have built a technology to unlock and explore the latest frontier in sweat diagnostics,” Prasad said. “This sweat-based, wearable technology from EnLiSense is truly transformational in that it can measure and report human host response messenger molecules associated with inflammation and infection in a real-time and continuous manner.”
The sensor uses passive sweat, which means that the wearer does not need to engage in physical activity or have their sweat glands expressed to generate a sample. Real-time continuous monitoring is possible as sweat is collected on a removable strip, which must be changed daily.
In this study, the researchers collected sweat from 18 healthy people who wore the sensor. They also drew blood from the subjects and compared the results.
Researchers next plan to evaluate the sensor in clinical studies with patients experiencing respiratory infections.
The first author of the study is Badrinath Jagannath PhD’21, who received a first-tier David Daniel Thesis Award from the Office of Graduate Education for his research on the sensor technology. He recently became a postdoctoral research fellow at the Wyss Institute at Harvard University.
Other authors include UT Dallas bioengineering research scientist Dr. Kai-Chun Lin; Dr. Madhavi Pali, a former UTD bioengineering research scientist; Devangsingh Sankhala PhD’21, a system engineer at Delart; Dr. Pejman Naraghi, senior consultant and subject matter expert at Tunnell Government Services; and Dr. Sriram Muthukumar, co-founder of EnLiSense, an Allen, Texas, company that develops lifestyle-based sensors and devices. Prasad, who is the corresponding author of the study, also is a co-founder of EnLiSense.
This project has been funded by a contract (HHSO100201800026C) awarded to EnLiSense LLC as part of the DRIVe initiative (Division of Research, Innovation, and Ventures), which was established by the Biomedical Advanced Research and Development Authority, part of the Assistant Secretary for Preparedness and Response within the Department of Health and Human Services.
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Materials provided by University of Texas at Dallas. Original written by Kim Horner. Note: Content may be edited for style and length.

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Older men with high body-mass index have more sperm cell irregularities

Single-cell analysis of autopsied human testes suggests that abnormalities associated with aging sperm cells might be exacerbated by elevated body mass index (BMI). The research appears May 2nd in the journal Developmental Cell.
Even though it is well established that older men display reduced reproductive health, testis aging remains poorly understood at the molecular and genomic level. Moreover, it has not been clear whether lifestyle or environmental factors affect this decline.
“Aging may confer a combination of modest molecular changes that sensitize the testis for additional dysregulation, with pronounced dysregulation caused when aging is combined with additional factors such as obesity,” says co-senior author Bradley Cairns of the University of Utah School of Medicine.
To address this gap, Cairns and co-senior study author Jingtao Guo, also of the University of Utah School of Medicine, used single-cell RNA sequencing to profile more than 44,000 cells obtained from autopsy testis samples from four young men and eight older men. The older donors were screened for having offspring as young adults to ensure early-adult fertility.
The young samples clustered together and did not display molecular signatures of aging or a disrupted ability to produce sperm cells. Surprisingly, the older samples showed only modest age-related changes in stem cells that give rise to mature sperm, but were clearly classified into two distinct groups. The first group displayed an intact ability to produce sperm cells, with only weak molecular signatures that distinguished them from young samples. By contrast, the second group showed a very limited ability to develop sperm cells.
Notably, BMI emerged as a critical factor among older individuals. All donors from the first group had levels lower than 27, whereas all donors from the second group had levels higher than 30. Taken together, the results reveal possible molecular mechanisms underlying the complex testicular changes associated with aging, and their possible exacerbation by concurrent chronic conditions such as obesity.
Moving forward, larger patient cohorts are needed to fully validate the results. Another avenue for future research is to explore whether the testicular cells of older, heavy-set males show unique aging signatures, or whether they simply display accelerated aging. It is also not clear whether diet, exercise, diabetes, or altered hormone production play a role in testis aging. In addition, determining at what age the dysregulation of supporting testis cells emerges, and whether and how it may be reversible, may lead to improved medical guidance for older men.
“Our study reveals potential biomarkers for diagnosis of testis aging and directions for potential treatment of aging-related subfertility,” says Guo. “It also serves as a foundational dataset for the scientific community to study how human testis and fertility respond to aging.”
This work was supported by the National Institute on Aging.
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He Spurred a Revolution in Psychiatry. Then He ‘Disappeared.’

In 1972, Dr. John Fryer risked his career to tell his colleagues that gay people were not mentally ill. His act sent ripples through the legal, medical and justice systems.On the second day of the annual convention of the American Psychiatric Association in 1972, something extraordinary happened.While the assembled psychiatrists, mostly white men in dark suits, settled into rows of chairs in the Danish Room at the Adolphus Hotel in Dallas, a disguised figure had been smuggled through the back corridors. At the last minute, he stepped through a side curtain and took his place at the front of the room.There was an intake of breath in the audience. The man’s appearance was grotesque. His face was covered by a rubber Nixon mask, and he was wearing a garish, oversized tuxedo and a curly fright wig. But the outlandishness of his outfit diminished in importance once he began to speak.“I am a homosexual,” he began. “I am a psychiatrist.”For the next 10 minutes, Henry Anonymous, M.D. — this is what he had asked to be called — described the secret world of gay psychiatrists. Officially, they did not exist; homosexuality was categorized as a mental illness, so acknowledging it would result in the revocation of one’s medical license, and the loss of a career. In 42 states, sodomy was a crime.The reality was that there were plenty of gay people in the A.P.A., psychiatry’s most influential professional body, the masked doctor explained. But they lived in hiding, concealing every trace of their private life from their colleagues.“All of us have something to lose,” he said. “We may not be under consideration for a professorship; the analyst down the street may stop referring us his overflow; our supervisor may ask us to take a leave of absence.”This was the trade-off that had formed the basis of the masked man’s life. But the cost was too high. That’s what he had come to tell them.“We are taking an even bigger risk, however, in not living fully our humanity,” he said. “This is the greatest loss, our honest humanity.”He took his seat to a standing ovation.Dr. Fryer’s speechListen to Dr. Fryer deliver his remarks in their entirety as “Dr. Henry Anonymous,” May 2, 1972.The 10-minute speech, delivered 50 years ago Monday, was a tipping point in the history of gay rights. The following year, the A.P.A. announced that it would reverse its nearly century-old position, declaring that homosexuality was not a mental disorder.It is rare for psychiatrists to transform the culture that surrounds them, but that is what happened in 1973.By removing the diagnosis from the Diagnostic and Statistical Manual of Mental Disorders, or D.S.M., psychiatry removed the legal basis for a wide range of discriminatory practices: for denying gay people the right to employment, citizenship, housing and the custody of children; for excluding them from the clergy and the military and the institution of marriage. The long process of rolling back those practices could begin.When referred to psychiatrists, gay people would no longer be sent to be “cured” — injected with hormones, subjected to aversion therapy or pored over by analysts — but instead told that, from the point of view of science, there was nothing intrinsically wrong with them.The Great ReadMore fascinating tales you can’t help but read all the way to the end.One hundred years ago, the British spy Cruxy O’Connor was caught in what appears to be the I.R.A.’s only authorized attack on American soil.​​Here’s how Viola Davis drew on a life of private hardship to become one of the greatest actors of her generation.The tale is oft-repeated: A lover of Shakespeare released dozens of European starlings in New York City as an ode to the Bard, starting a North American invasion. Crucial parts of the story are not true.After delivering his speech, the man in the mask, John Ercel Fryer, 34, flew from Dallas to his home in Philadelphia, noting in his journal just how terrifying and profound the experience had been.“The day has passed, it has come and gone and I am still alive. For the first time I have identified with a force that is akin to my selfhood,” he wrote, in excerpts included in “Cured,” a 2018 documentary.Still — he didn’t tell his mother he had done it. He didn’t tell his sister. He didn’t tell his closest childhood friend. He barely told anybody for 20 years.‘What the hell is going on here?’Dr. Fryer in an undated yearbook photo from Transylvania University, where he was pre-med.Transylvania UniversityDr. Fryer, circa 1990, when he was a professor at Temple University.Historical Society of PennsylvaniaDr. Fryer, who died in 2003 at the age of 65, stood out for his size (he was 6-foot-4 and 300 pounds), for his flashing intelligence, and for the fact that he was obviously gay.Betty Lollis, a friend from Winchester, Ky., recalled him as the round-faced boy who was led into her second-grade class, dressed by his mother in a sailor suit. He was a prodigy, she said, and also “just a boy the boys laughed at or teased.”Decades later, Ms. Lollis said, some of their classmates apologized to Dr. Fryer for the way they had treated him. “These people that were painful for him were also all he had,” she said. “Those are his dearest friends.”He sailed through his classes, enrolling in college at 15 and medical school at 19. But again and again, his path was blocked when supervisors learned he was gay.The most crushing of these setbacks occurred in 1964. He had relocated to the freer atmosphere of the East Coast, and was a few months into a residency at the University of Pennsylvania when he let his guard down, telling a family friend at dinner that he was gay.The young man immediately reported this to his father, who reported it to the department chairman at Penn, Dr. Fryer said in a 2002 interview with the Journal of Gay and Lesbian Psychiatry. The department chairman called Dr. Fryer into his office and said: “You can either resign or I’ll fire you.”It took years of humiliating assignments at a state-run psychiatric hospital, the only institution that accepted him, for Dr. Fryer to complete his residency. After that he faced a long, uncertain path to tenure. For these reasons, coming out had little appeal, he said in a 2001 interview for “This American Life,” much of which has not been published until now.“It was a way, if you came out as gay, to not have any power,” he said. “And I wanted to be powerful. So being a straight, closeted physician enabled me to have power.”In 1970, Frank Kameny, an astronomer who had been dismissed from the military because he was gay, led a small group of gay rights activists to protest the A.P.A.’s annual convention, demanding that the diagnosis be declassified.Dr. Fryer was a full-fledged member of the “Gay P.A.,” a group of closeted A.P.A. members. who gathered in secret on the edges of the association, and he watched with distaste as the protesters stormed into panel discussions and heckled the speakers. “I was embarrassed by it, and I wished that they would shut up,” he said.But the following year, Barbara Gittings, one of the activists, approached Dr. Fryer to ask for his help.Younger, more progressive leaders were rising through the ranks of the A.P.A., and the activists sensed an opening. They had an idea: Instead of picketing, they could shake things up by confronting the psychiatrists with one of their own, a gay psychiatrist. If only they could find someone who would agree to do it.Ms. Gittings, left, at a “Gay, Proud and Healthy” display at the Dallas convention in 1972.Kay Tobin/Manuscripts and Archives Division, The New York Public Library“My first reaction was: No way,” Dr. Fryer recalled. “I had no security, and I did not want to do anything to jeopardize the possibility that I could get a faculty position somewhere. There was no way at that point that I was going to do that as an open thing.”Over the months that followed, though, Ms. Gittings kept calling. She updated Dr. Fryer as she approached a dozen of his gay colleagues and each said no, the risk was too great.Their refusals bothered Dr. Fryer. And Ms. Gittings, as he put it, kept “upping the ante.” What if she paid his way to Dallas? What if he wore a disguise, so that no one knew it was him?“She planted in my mind the possibility that I could do something,” he said. “And that I could do something that would be helpful without ruining my career.”Dr. Fryer’s lover at the time was a drama student, and the two threw themselves into the project of devising a disguise that would conceal his identity: a vastly oversized tuxedo, a rubber mask melted to distort its features, and a wig with a low hairline opposite to his own.Stepping onto the stage that day, Dr. Fryer said, “I felt a great freedom, a great sense of freedom.”There was pride, too, that he was the only one of his colleagues who dared.“To do that thing, to be willing to do that thing, when none of my colleagues in the Gay P.A. would be wiling to do it, openly or otherwise,” he said. “They were all in the audience. They were clapping.”The sight of Dr. Fryer had a powerful emotional effect on the psychiatrists gathered in the room, said Dr. Saul Levin, who in 2013 became the first openly gay man to serve as the A.P.A.’s chief executive and medical director.“It obviously really shook them,” he said. “Here was this huge audience for the time, seeing someone come out in a very weird costume. It made them a little disoriented — what the hell is going on here? And then this person comes out with such an eloquent speech.”Dr. Fryer was giddy as he left the stage, so exhilarated that, before returning to Philadelphia, he splurged on a manual harpsichord, which he wryly described as “among the least wise choices of my life.”As he returned to his hotel room to change out of his disguise, he passed the chairman of the psychiatry department at the University of Pennsylvania, who had fired him from his residency. Neither man showed any sign of recognition.‘It was over for me’Dr. Fryer in his Germantown home with one of his Doberman pinschers, circa 1975.Harry Adamson, via Historical Society of PennsylvaniaDr. Fryer returned to the rambling, Victorian house where he lived in Germantown with his Doberman pinschers and the medical students he took in as boarders.He remained himself — by turns generous and overbearing, charismatic and acerbic, switching on his Kentucky accent when it suited him.He still didn’t have tenure, and his career path was as tenuous as ever. In 1973, the A.P.A. voted to declassify homosexuality. And Dr. Fryer lost another job, this one at Friends Hospital.Again, an administrator called him into his office. “If you were gay and not flamboyant, we would keep you,” Dr. Fryer recalled him saying. “If you were flamboyant and not gay, we would keep you. But since you are both gay and flamboyant, we cannot keep you.”Dr. Fryer watched as his colleagues got promoted and won tenure. The Gay P.A. faded, as a new, more activist generation stepped forward as an open force within psychiatry, forming the Association of Gay and Lesbian Psychiatrists. But Dr. Fryer took no part in it.“I ran away again,” he said. “I didn’t go to the meetings. It was like I just sort of disappeared.” It was as if, he said, “I had done my thing and it was over for me.”Every now and then, he would tell someone about what he had done.Dr. Karen Kelly, 67, who rented a room from Dr. Fryer as a medical student, said he told her over dinner some time in the late 1970s, and never mentioned it again.Ms. Lollis, 85, said she and Dr. Fryer confided in one another later in life, sometimes speaking on the phone several times a week. But she didn’t find out that he was Dr. Anonymous until 2002, when he sent her the episode of “This American Life” that described the speech.“He just didn’t share it with anyone,” she said. “Not his mother, not his sister.”Circa 1970. Dr. Fryer was a musician and a choirmaster of his local church for 30 years.Historical Society of PennsylvaniaAt Temple University with colleagues around 1975.Historical Society of PennsylvaniaDr. Fryer would eventually get tenure at Temple University, where he built a specialty in bereavement and helped pioneer the hospice movement. After teaching all day and having dinner, he would often see patients until 11 p.m., Dr. Kelly recalled. He sat with many of his patients while they were dying.He threw big parties, and sometimes his famous friends, like the anthropologist Margaret Mead or the writer Gail Sheehy, would show up. He wore dashikis. Traveling for conferences, “he’d end up in a tiki restaurant with my cousins, dancing with the hula dancer,” Dr. Kelly said.But a sense of resentment clung to him, said Dr. David Scasta, who got to know Dr. Fryer as a medical resident at Temple University and interviewed him about his life in 2002.He felt isolated from the gay community, said Dr. Scasta, a past president of the Association of Gay and Lesbian Psychiatrists. He never had a long-term relationship. And he always felt that his career was not what it could have been.“There was always a sense of sadness at not being fully accepted,” he said. “John always felt he was on the fringe.”Decades would pass before historians of gay rights fully understood the significance of the Dr. Anonymous speech, that it had “a Stonewall riots kind of importance,” Dr. Scasta added. In that case, too, the surge of forward motion was driven by unlikely people.“It’s not always the law-abiding, nice people who did it, it’s the ones who are on the periphery who can make change,” he said.On Monday, the 50th anniversary of the Dr. Anonymous speech will be celebrated with speeches and proclamations in Philadelphia, which has declared May 2 John Fryer Day.Public celebration of his act had already begun in the years before Dr. Fryer’s death, and in 2001 he remarked on it caustically, saying he “sort of was trundled out as an exhibit every time someone wanted an exhibit.”At the time, though, it was secrecy that gave his act its power, he said.“As this person who was in disguise, I could say whatever I wanted,” he said, adding, “I did this one isolated event, which changed my life, which helped change the culture in my profession, and I disappeared.”

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Study finds children with vegetarian diet have similar growth and nutrition compared to children who eat meat

A study of nearly 9,000 children found those who eat a vegetarian diet had similar measures of growth and nutrition compared to children who eat meat. The study, published in Pediatrics and led by researchers at St. Michael’s Hospital of Unity Health Toronto, also found that children with a vegetarian diet had higher odds of underweight weight status, emphasizing the need for special care when planning the diets of vegetarian kids.
The findings come as a shift to consuming a plant-based diet grows in Canada. In 2019, updates to Canada’s Food Guide urged Canadians to embrace plant-based proteins, such as beans and tofu, instead of meat.
“Over the last 20 years we have seen growing popularity of plant-based diets and a changing food environment with more access to plant-based alternatives, however we have not seen research into the nutritional outcomes of children following vegetarian diets in Canada,” said Dr. Jonathon Maguire, lead author of the study and a pediatrician at St. Michael’s Hospital of Unity Health Toronto.
“This study demonstrates that Canadian children following vegetarian diets had similar growth and biochemical measures of nutrition compared to children consuming non-vegetarian diets. Vegetarian diet was associated with higher odds of underweight weight status, underscoring the need for careful dietary planning for children with underweight when considering vegetarian diets.”
Researchers evaluated 8,907 children age six months to eight years. The children were all participants of the TARGet Kids! cohort study and data was collected between 2008 and 2019. Participants were categorized by vegetarian status – defined as a dietary pattern that excludes meat – or non-vegetarian status.
Researchers found children who had a vegetarian diet had similar mean body mass index (BMI), height, iron, vitamin D, and cholesterol levels compared to those who consumed meat. The findings showed evidence that children with a vegetarian diet had almost two-fold higher odds of having underweight, which is defined as below the third percentile for BMI. There was no evidence of an association with overweight or obesity.
Underweight is an indicator of undernutrition, and may be a sign that the quality of the child’s diet is not meeting the child’s nutritional needs to support normal growth. For children who eat a vegetarian diet, the researchers emphasized access to healthcare providers who can provide growth monitoring, education and guidance to support their growth and nutrition.
International guidelines about vegetarian diet in infancy and childhood have differing recommendations, and past studies that have evaluated the relationship between vegetarian diet and childhood growth and nutritional status have had conflicting findings.
“Plant-based dietary patterns are recognized as a healthy eating pattern due to increased intake of fruits, vegetables, fiber, whole grains, and reduced saturated fat; however, few studies have evaluated the impact of vegetarian diets on childhood growth and nutritional status. Vegetarian diets appear to be appropriate for most children,” said Dr. Maguire, who is also a scientist at MAP Centre for Urban Health Solutions at St. Michael’s Hospital.
A limitation of the study is that researchers did not assess the quality of the vegetarian diets. The researchers note that vegetarian diets come in many forms and the quality of the individual diet may be quite important to growth and nutritional outcomes. The authors say further research is needed to examine the quality of vegetarian diets in childhood, as well as growth and nutrition outcomes among children following a vegan diet, which excludes meat and animal derived products such as dairy, egg, and honey.
The study was funded by the Canadian Institutes of Health Research (CIHR), St. Michael’s Hospital Foundation and SickKids Foundation.
Story Source:
Materials provided by St. Michael’s Hospital. Original written by Jennifer Stranges. Note: Content may be edited for style and length.

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