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TAU Scientists Print First 3D Heart Using Patient’s Own Cells and Materials

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Engineered heart completely matches the immunological, cellular, biochemical and anatomical properties of the patient

In a major medical breakthrough, Tel Aviv University researchers have “printed” the world’s first 3D vascularised engineered heart using a patient’s own cells and biological materials. Their findings were published on April 15 in a study in Advanced Science.

Until now, scientists in regenerative medicine — a field positioned at the crossroads of biology and technology — have been successful in printing only simple tissues without blood vessels.

“This is the first time anyone anywhere has successfully engineered and printed an entire heart replete with cells, blood vessels, ventricles and chambers,” says Prof. Tal Dvir of TAU’s School of Molecular Cell Biology and Biotechnology, Department of Materials Science and Engineering, Center for Nanoscience and Nanotechnology and Sagol Center for Regenerative Biotechnology, who led the research for the study.

Heart disease is the leading cause of death among both men and women in the United States. Heart transplantation is currently the only treatment available to patients with end-stage heart failure. Given the dire shortage of heart donors, the need to develop new approaches to regenerate the diseased heart is urgent.

“This heart is made from human cells and patient-specific biological materials. In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models,” Prof. Dvir says. “People have managed to 3D-print the structure of a heart in the past, but not with cells or with blood vessels. Our results demonstrate the potential of our approach for engineering personalized tissue and organ replacement in the future.”

Research for the study was conducted jointly by Prof. Dvir, Dr. Assaf Shapira of TAU’s Faculty of Life Sciences and Nadav Moor, a doctoral student in Prof. Dvir’s lab.

 

​”At this stage, our 3D heart is small, the size of a rabbit’s heart,” explains Prof. Dvir. “But larger human hearts require the same technology.”

The secret to a new heart

For the research, a biopsy of fatty tissue was taken from patients. The cellular and a-cellular materials of the tissue were then separated. While the cells were reprogrammed to become pluripotent stem cells, the extracellular matrix (ECM), a three-dimensional network of extracellular macromolecules such as collagen and glycoproteins, were processed into a personalized hydrogel that served as the printing “ink.”

After being mixed with the hydrogel, the cells were efficiently differentiated to cardiac or endothelial cells to create patient-specific, immune-compatible cardiac patches with blood vessels and, subsequently, an entire heart.

According to Prof. Dvir, the use of “native” patient-specific materials is crucial to successfully engineering tissues and organs.

“The biocompatibility of engineered materials is crucial to eliminating the risk of implant rejection, which jeopardizes the success of such treatments,” Prof. Dvir says. “Ideally, the biomaterial should possess the same biochemical, mechanical and topographical properties of the patient’s own tissues. Here, we can report a simple approach to 3D-printed thick, vascularized and perfusable cardiac tissues that completely match the immunological, cellular, biochemical and anatomical properties of the patient.”

What organ would you like?

The researchers are now planning on culturing the printed hearts in the lab and “teaching them to behave” like hearts, Prof. Dvir says. They then plan to transplant the 3D-printed heart in animal models.

“We need to develop the printed heart further,” he concludes. “The cells need to form a pumping ability; they can currently contract, but we need them to work together. Our hope is that we will succeed and prove our method’s efficacy and usefulness.

 

“Maybe, in ten years, there will be organ printers in the finest hospitals around the world, and these procedures will be conducted routinely.”

Better maps for better self-driving cars?

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New research on object detection breaks with long-held principles of radar technologies

Radar technologies were originally designed to identify and track airborne military targets. Today they’re more often used to detect motor vehicles, weather formations and geological terrain.

Until now, scientists have believed that radar accuracy and resolution are related to the range of frequencies or radio bandwidth used by the devices. But a new Tel Aviv University study finds that an approach inspired by optical coherence tomography (OCT) requires little to no bandwidth to accurately create a high-resolution map of a radar’s surrounding environment.

“We’ve demonstrated a different type of ranging system that possesses superior range resolution and is almost completely free of bandwidth limitations,” says Prof. Pavel Ginzburg of TAU’s School of Electrical Engineering, one of the principal authors of the study. “The new technology has numerous applications, especially with respect to the automotive industry. It’s worth noting that existing facilities support our new approach, which means that it can be launched almost immediately.”

The new study was conducted jointly by Prof. Ginzburg, Vitali Kozlov, Rony Komissarov and Dmitry Filonov, all of TAU’s School of Electrical Engineering. 

Preventing the traffic jams of the future

It was commonly believed that radar resolution was proportional to the bandwidth used. Meaning, a good, accurate radar, required a lot of bandwidth, something that could become a limited resource in the future.

“Our concept offers solutions in situations that require high-range resolution and accuracy but in which the available bandwidth is limited, such as the self-driving car industry, optical imaging and astronomy,” Kozlov explains. “Not many cars on the road today use radars, so there’s almost no competition for allocated frequencies. But what will happen in the future, when every car will be equipped with a radar and every radar will demand the entire bandwidth?

“We’ll find ourselves in a sort of radio traffic jam. Our solutions permit drivers to share the available bandwidth without any conflict,” Kozlov says.

The TAU researchers have now demonstrated that low-bandwidth radars can achieve similar performance at a lower cost and without broadband signals by exploiting the coherence property of electromagnetic waves. The new “partially coherent” radar, which uses significantly less bandwidth, is as effective as a standard “coherent” radars in experimental situations.

Using radar for rescue

“Our demonstration is just the first step in a series of new approaches to radiofrequency detectors that explore the impact of low-bandwidth radars on traditional fields,” Prof. Ginzburg concludes. “We intend to apply this technology to previously unexplored areas, like rescue operations — sensing if an individual is buried in a collapsed building — or street mapping — sensing if a child is about to cross the street behind a bus that conceals him.”

Research for the study was supported by an ERC grant and Kamin, and it was conducted at TAU’s Radio Physics Laboratory’s anechoic chamber.

New genetically encoded sensor isolates hidden Leukemic cells

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Cells express surface markers that help them escape most targeted therapies, Tel Aviv University researchers say

Understanding how leukemic stem cells are regulated has become an important area of cancer research. All stem cells can multiply, proliferate and differentiate. Because of these qualities, leukemic stem cells are the most malignant of all leukemic cells. 

A team of Tel Aviv University researchers have now devised a novel biosensor that can isolate and target leukemic stem cells. The research team, led by Dr. Michael Milyavsky of the Department of Pathology at TAU’s Sackler School of Medicine, discuss their unique genetically encoded sensor and its ability to identify, isolate and characterize leukemic stem cells in a study published on January 31 in Leukemia.

Raising the survival rate for blood cancers

“The major reason for the dismal survival rate in blood cancers is the inherent resistance of leukemic stem cells to therapy,” Dr. Milyavsky says. “But only a minor fraction of leukemic cells have high regenerative potential, and it is this regeneration that results in disease relapse. A lack of tools to specifically isolate leukemic stem cells has precluded the comprehensive study and specific targeting of these stem cells until now.”

Until recently, cancer researchers used markers on the surface of the cell to distinguish leukemic stem cells from the bulk of cancer cells, with only limited success. “There are hidden cancer stem cells that express differentiated surface markers despite their stem cell function. This permits those cells to escape targeted therapies,” Dr. Milyavsky explains. “By labeling leukemia cells on the basis of their stem character alone, our sensor manages to overcome surface marker-based issues.

“We believe that our biosensor can provide a prototype for precision oncology efforts to target patient-specific leukemic stem cells to fight this deadly disease.”

Personalized medical testing

The scientists searched genomic databases for “enhancers,” the specific regulatory regions of the genome that are particularly active in stem cells. Then they harnessed genome engineering to develop a sensor composed of a stem cell active enhancer fused with a fluorescence gene that labels the cells in which the enhancer is active.

The scientists were also able to demonstrate that sensor-positive leukemia stem cells are sensitive to a known and inexpensive cancer drug called 4-HPR (fenretinide), providing a novel biomarker for patients who can potentially benefit from this drug.

“Using this sensor, we can perform personalized medicine oriented to drug screens by barcoding a patient’s own leukemia cells to find the best combination of drugs that will be able to target both leukemia in bulk as well as leukemia stem cells inside it,” Dr. Milyavsky concludes. “We’re also interested in developing killer genes that will eradicate specific leukemia stem cells in which our sensor is active.”

The researchers are now investigating those genes that are active in leukemic stem cells in the hope finding druggable targets.

When Harry met Zahava

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TAU expert on post-military combat trauma, Prof. Zahava Solomon, speaks at the Veterans’ Mental Health Conference in London

TAU’s Prof. Zahava Solomon discussed issues relating to the long term trauma of military combatants with HRM Prince Harry, the Duke of Sussex, at the 2019 Veterans’ Mental Health Conference held at King’s College London. Prof. Solomon was one of a select number of international experts on trauma who presented at the conference. The participants’ goal was to share ideas about how best to support the psychological wellbeing of former military personnel.

The Duke, who served two tours in Afghanistan, discussed the long-term effects of military service with several speakers, praising their work. He is a regular champion of mental health advocacy through his work with the Royal Foundation’s ‘Heads Together’ project, which aims to promote a national conversation on the topic.

Solomon spoke with Prince Harry about the findings of her study that she presented and mainly about the psychological effects of participating in combat – not only on the mental health of the combatants themselves but also on their families. The Prince expressed great interest and concern for the safety of soldiers.

Prof. Zahava Solomon​

“I expressed my appreciation and admiration in the name of mental health professionals inIsrael for his involvement and sensitivity, both because of his social standing and also because of his past as a combatant,” said Solomon, an Israel Prize laureate and a retired Lieutenant-Colonel in the Israel Defense Forces. “He said he could relate to the challenges based on his own experience. For someone in his position to come forward and say it’s quite normal to be traumatized, is really beneficial.”​

​In an interview with Forces TV, Solomon said: “For many veterans, the war starts when the shooting stops. Even 20 years after the war, we have actually observed the trauma – both psychological and physical – being suffered by the traumatized combatants. And on top of that, there are individuals who did not initially succumb to stress on the battlefield, but later on, over a period of 20 years, have actually developed late onset post-traumatic stress disorder.”

Prof. Solomon heads the I-CORE Research Center for Mass Trauma at Tel Aviv University. Formerly, she held roles as Head of Research in Mental Health in the IDF Medical Corps, Head of TAU’s Bob Shapell School of Social Work, and Head of TAU’s Adler Research Center for Child Welfare and Protection. She has published over 400 academic articles and seven books. Her studies of trauma among combat veterans, prisoners of war and Holocaust survivors spans over four decades and are unparalleled in scope, depth and breath. Her work helps shape the psychosocial treatment and rehabilitation of traumatized soldiers and their families.

Featured image: Prince Harry, the Duke of Sussex discusses post-military combat trauma. Credit: Daniel Leightley/Dan Dyball

A unique collaboration for Blockchain Applications at the Coller School of Management

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This is a special opportunity for researchers at the Coller School of Management and Tel Aviv University to carry out blockchain and crypto currency research in cooperation with international industry.

The blockchain technology enables secure business activity on the internet and commercial undertakings between various parties, without the necessity for a central managerial entity – this managerial function being replaced by encrypted blocks of information.  A few months ago the Coller School of Management at Tel Aviv University established the first venture of this kind in Israel – the Hogeg Institute for Blockchain Applications, with the aim of advancing research, teaching and distribution of information in the area of blockchain technology.

As part of the activities of the Institute, a unique collaboration was created when the the Hogeg Institute for Blockchain Applications signed an agreement with the Frankfurt School Blockchain Center to support academic research in the area of blockchain technology and crypto currencies.  The project is being financed by Accelerator Frankfurt GmbH, which leads the Fintech/Blockchain area in Germany and focuses its activities on introducing the digital B2B technologies into the financial sector, in cooperation with Santiment Deutschland, a well-known success story in the area of crypto currencies that provides access to a unique platform for storing data and enables its use for academic research.

Dr Jacob Mendel, Managing Director of the Hogeg Institute for Blockchain Applications explains:  “This is a groundbreaking venture in academic cooperation to advance blockchain research focusing on providing economic and business solutions that will contribute to activity on the cutting edge of international research in which a number of institutions at leading universities throughout the world such as Stanford and Columbia participate.”

Maria Pennanen, CEO of Santiment Deutschland, adds:  “We want to get students and researchers together to analyze and understand the crypto currency market data.  As a first stage, the cooperation will focus on academic work.  We will hold the first academic event in the crypto area, under the title ‘Academia Meets the Market Players’, where we will present our initial findings.”

Ram Shoham, founder of Accelerator Frankfurt:  “It is an honor for us to start this cooperation with the Hogeg Institute for Blockchain Applications.  We believe in caring for the global blockchain eco-system through cooperative ventures and partnerships.”

Prof. Dan Amiram, Associate Dean of the Coller School of Management at Tel Aviv University and Head of the Hogeg Institute for Blockchain Applications:  “This is a special opportunity for researchers from Tel Aviv University to carry out projects in cooperation with international industry that contends with new challenges and applies the technology in a range of areas of activity.”

Our very best wishes go to the students and researchers at Tel Aviv University and the Coller School of Management who are participating in this special research project in the blockchain and crypto-currency area in cooperation with international industry.

What’s in a pi?

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March 14h is International Pi Day. Why do we celebrate it? Is pi still relevant 4,000 years after being discovered? And is peach pie better than cherry?

What’s the best kind of pie? And what’s the perfect crust-to-filling ratio? Mankind has been struggling with these questions since the dawn of baked goods, which is probably about as long as the number pi has been known to us.

Although Pi Day was first celebrated in the 1980s, the number pi (represented as the Greek letter π) was first discovered about 4,000 years ago. The ratio of a circle’s circumference to the circle’s diameter, pi is always the same, whether you’re measuring a penny or a truck tire. Not only that, but pi is an “irrational” number – no matter how many digits of pi we calculate, we’ll never be able to predict which digit comes next. 

We decided to ask Ofir Gorodetsy, a PhD student at the School of Mathematical Sciences at Tel Aviv University, about the significance of pi.

“The decimal expansion of π starts with 3.14,” Ofir said. “Which is why we celebrate Pi Day on March 14th every year. And aside from being known to Ancient Egyptians and Babylonians, pi is also mentioned in the Hebrew Bible, where the approximation 3 is used to measure the circumference of a circle.”

Too much pi?

Although most people are familiar with pi as being 3.14, mathematicians have been struggling to find the other digits of pi for centuries. According to Ofir, “figuring out the digits of pi gets pretty difficult after a dozen or so. Many scholars from all over the world have tried to find more and more digits: Archimedes, Liu Hui, Brahmagupta, Fibonacci, Isaac Newton. In the 18th century a mathematician even came up with proof that the digits of pi don’t follow any pattern, so they never repeat in any predictable way.”

According to Ofir, figuring out the digits of pi is much easier these days. Even freshmen at university can calculate as many digits as they’d like, using modern tools.

But the magic of pi is not only its length, but how common it is in the natural world. The disk of the sun, the pupil of our eyes, the ripples in a pond, even the way rivers tend to bend and flow can be described using pi. It’s used in the work of biologists, engineers, geographers, physicsts, mathematicians. Almost every discipline that deals with the world around us crosses paths with this unique number at some point. 

So why do we celebrate Pi Day? Probably because math is at its most delicious when it’s fresh out of the oven.

New blood test could detect genetic disorders during first trimester

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Test could map the fetal genome and detect innumerable diseases caused by minuscule impairments, Tel Aviv University researchers say

Tel Aviv University researchers have developed a new blood test for genetic disorders that may allow parents to learn about the health of their baby as early as 11 weeks into pregnancy.

The simple blood test lets doctors diagnose genetic disorders in fetuses early in pregnancy by sequencing small amounts of DNA in the mother’s and the father’s blood. A computer algorithm harnessing the results of the sequencing would then produce a “map” of the fetal genome, predicting mutations with 99% or better accuracy depending on the mutation type.

Prof. Noam Shomron of TAU’s Sackler School of Medicine led the research, which was conducted by TAU graduate student Tom Rabinowitz with Avital Polsky, Artem Danilevsky, Guy Shapira and Chen Raff, all from Prof. Shomron’s lab. The study is a collaboration with Dr. David Golan of the Technion-Israel Institute of Technology and Prof. Lina Basel-Salmon and Dr. Reut Tomashov-Matar of Rabin Medical Center. It was published on February 20 in the journal Genome Research.

A safe and simple procedure

“Noninvasive prenatal tests are already available for chromosome disorders such as Down syndrome,” Prof. Shomron says. “Our new procedure is based on fetal DNA fragments that circulate freely in maternal blood and bears only a minimal risk for the mother and fetus compared with such invasive techniques as the amniotic fluid test. We will now be able to identify numerous mutations and diseases in a safe and simple procedure available at the doctor’s office.

“The genetic mechanism behind Down syndrome affects a very large portion of the genome and therefore is easier to detect,” Prof. Shomron explains. “We performed upgraded noninvasive fetal genotyping, using a novel approach and an improved algorithm, to detect many other diseases that are caused by smaller parts of the genome. This is like looking at a map of the world and noticing not only that a continent is missing, but also that a single house is missing.

“The practical applications are endless: a single blood test that would detect a wide range of genetic diseases, such as Tay-Sachs disease, cystic fibrosis and many others.”

An algorithm for DNA

Prof. Shomron and colleagues tested blood samples from three families at Rabin Medical Center in the 11th week of gestation. They extracted maternal and paternal DNA from their white blood cells and fetal DNA from a placental cell sample. They also extracted circulating cell-free fetal DNA from the maternal blood.

“We sequenced all these DNA samples and created a computer algorithm that utilizes the parental DNA as well as the cell-free fetal DNA to reconstruct the fetal genome and predict mutations,” says Prof. Shomron. “We compared our predictions to the true fetal DNA originating from the placenta. Our model is the first to predict small inherited insertions and deletions. The method described can serve as a general framework for noninvasive prenatal diagnoses.”

The researchers are working on further improving the accuracy of the method and extending it to detect even more types of mutations.

 

 

TAU scholar named Knight of the Order of Arts and Letters

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Dr. Sefy Hendler received the highest decoration awarded by the French Ministry of Culture

Dr. Sefy Hendler, head of the Department of Art History at Tel Aviv University, has been named Knight of the Order of Arts and Letters, one of the highest decorations awarded by the French Ministry of Culture. The title was given to him for “his commitment to the service of French culture”.

He received the decoration from the hands of the French Ambassador to Israel, Mrs. Hélène Le Gal, during a ceremony that took place on February 18, at the French Embassy in Tel Aviv.

“I think that in our country, fed by American culture, there is room for other voices,” he said. “The French voice, according to which I have been educated for many years, is among the most important, especially because it is different, and I wish that my students, as well as the other people who come to the University, will be exposed to this aspect of culture “.

Personalities who received this award in the past include British poet and playwright T. S. Eliot, Bob Dylan, David Bowie, American writer Paul Auster, actress Sharon Stone, as well as Israeli authors Amos Oz, David Grossman, Ohad Naharin, Haim Gouri et Zeruya Shalev.

TAU Confers Honorary Doctorate on Pioneer in Internet Technology

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Prof. Amnon Yariv honored for decades of breakthrough research in optoelectronics

In recognition of his indelible mark in the field of integrated optics technology, Tel Aviv University awarded an honorary doctorate to Prof. Amnon Yariv, the Martin and Eileen Summerfield Professor of Applied Physics and Electrical Engineering at the California Institute of Technology (CalTech). The conferment ceremony was held at the Raya and Joseph Jaglom Auditorium in the George S. Wise Senate Building. Prof. Yariv is a member of and visiting lecturer at TAU’s Mortimer and Raymond Sackler Institute of Advanced Studies.

With a plethora of awards and honors, including the prestigious National Medal of Science presented by President Barak Obama in 2010, Prof. Yariv is widely credited with transforming the optical communications industry. His research group, which focuses on the theoretical and technological underpinning of optical communication, has generated numerous technologies, not the least of which was the invention of the semiconductor distributed feedback laser. This device enabled the transmission of mass data via phone, video, cable and the Internet, which has profoundly influenced society and culture across the globe.

Israeli-born Prof. Yariv fought in Israel’s War of Independence from 1948-1950, before leaving for the US. He completed his BSc, MSc and PhD in electrical engineering at the University of California, Berkeley, taking on his first role as Research Associate there in 1958. He then spent five years on the technical staff of Bell Telephone Laboratories, before returning to academia in 1964 as a professor of electrical engineering at CalTech, where he remains today.

In his tribute to Prof. Yariv, TAU Rector Yaron Oz spoke of how TAU awards honorary doctorates to those who are visionaries in their field — to those who create new realities instead of merely improving on what exists. “The ability to set a vision far beyond imagination and bridge the gap between vision and reality, this is the paths of excellence that led you here today,” said Prof. Oz.

Presenting the award along with Prof. Oz was TAU Vice President Raanan Rein. Among the guests in attendance were: Prof. Yossi Rosenwaks, Dean of the Iby and Aladar Fleischman Faculty of Engineering; Prof. Avraham Gover, Head, Israeli Free Electron Laser Knowledge Center for Radiation Sources and Applications, Faculty of Engineering;  and Prof. (Emeritus) Emanuel Marom, former Dean of Engineering.

Featured image: From left: Prof. Yaron Oz, Prof. Amnon Yariv and Prof. Raanan Rein Photo: Yehonatan Zur

Adolescents with Celiac disease at higher risk of eating disorders

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Teenage girls who are overweight and have Celiac Disease are at highest risk of developing eating disorders

Celiac disease is a chronic condition, characterized by inflammation and atrophy of the small intestine. It affects roughly 1 in 100 people, and a strict, lifelong gluten-free diet is the only remedy. A new Tel Aviv University study finds a link between the disaese and a higher incidence of disordered eating behavior during adolescence and young adulthood.

The researchers found that 19% of female teens and 7% of male teens with CD exhibited eating disorders, compared to 8% and 4% of adolescents who did not have CD. Disordered eating behaviors affect about 10% of adolescents and refer to a wide range of abnormal eating behaviors, including binge eating, dieting, skipping meals regularly, self-induced vomiting and obsessive calorie counting. These behaviors are most common among older, overweight female adolescents with CD.

The study was led by Dr. Itay Tokatly-Latzer of TAU’s Sackler Faculty of Medicine and the Department of Pediatrics at Chaim Sheba Medical Center. It was overseen by Dr. Orit Pinhas-Hamiel and conducted by Dr. Daniel Stein, Dr. Batia Weiss and Prof. Liat Lerner-Geva, all of TAU’s Sackler Faculty of Medicine. The results were published in Eating and Weight Disorders.

Early warning signs are crucial

“We discovered an increased occurrence of disordered eating behavior among adolescents with CD,” Dr. Tokatly-Latzer says. “Caregivers of Celiac patients should be aware of the possibility of them having eating disorders. Early recognition of this can prevent the deterioration of these states into full-blown disorders such as anorexia nervosa and bulimia.

“These eating patterns can lead to a failure to meet nutritional and metabolic needs, which cause severe impairment to psychosocial functioning,” Dr. Tokatly-Latzer continues. “Primary care physicians and gastroenterologists who encounter adolescents with CD should increase their awareness to the possibility of this population having disordered eating behavior. Once the suspicion is raised, they can refer them for psychological and nutritional treatment.”

The researchers conducted a web-mediated survey on 136 adolescents aged 12-18 with CD. The survey assessed the participants’ rate of disordered eating behavior as well as their adherence to a gluten-free diet. The survey, conducted over the course of a year, included two self-rating questionnaires: the Eating Attitudes Test-26 and the gluten-free diet questionnaire. Only 32% of the participants reported a strict adherence to a gluten-free diet.

What medical teams should watch for

“Eating disorders have a perplexing etiology that includes biological, sociological, psychological and environmental elements,” Dr. Tokatly-Latzer explains. “Not only does the excessive preoccupation with food increase the likelihood of individuals with Celiac to develop eating disorders, but there is a major aspect that involves food limitation of any kind that probably triggers a predisposition for developing pathological eating tendencies.

“This study should raise awareness for medical teams to the importance of closely monitoring adolescents with CD for disordered eating behavior, especially when they are female, overweight or older. Since individuals with disordered eating behavior are at increased risk of developing a clinical form of an eating disorder, early identification and intervention may improve therapeutic outcomes.”

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