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After working with wounded Israeli soldiers in the 1970s, he developed a holistic approach to helping patients regain some semblance of the life they had before.Yehuda Ben-Yishay, a psychologist whose experience working with wounded Israeli soldiers led him to make pioneering advances in treating traumatic brain injuries, helping countless patients return to some semblance of the life they had before, died on March 24 at the NYU Langone Health hospital in Manhattan. He was 88.His death was confirmed by his wife, Myrna Ben-Yishay, a genetic counselor.Before Dr. Ben-Yishay developed what he called holistic cognitive therapy in the 1970s, most scientists thought that the adult brain was immutable, and that serious injuries — and the behavioral changes that resulted — were permanent.Working with Leonard Diller, his colleague at Rusk Rehabilitation at NYU Langone Health, Dr. Ben-Yishay proved otherwise, setting aside the biology of the brain to show that things like attention, memory and behavior could still be strengthened, or compensated for, in recovering patients.The two first demonstrated their ideas in Israel, where hundreds of soldiers, many of them tank drivers, had suffered traumatic brain injuries in the sprawling tank battles across the Sinai Desert and in the Golan Heights during the Yom Kippur War in 1973.They engaged about a dozen patients in what Dr. Ben-Yishai described as a therapeutic milieu. It wasn’t enough for a doctor to work one-on-one with a patient; everyone from nurses to families to other patients had to be involved in creating a safe environment in which a patient could address a brain injury and its consequences and start to regain or compensate for damaged cognitive skills.The two doctors returned to New York and in 1978 Dr. Ben-Yishay put their experience into practice with the NYU Rusk Holistic Day Program. A talented storyteller with a flair for drama, he was renowned for his ability to engage with patients, and he personally treated hundreds over the next four decades.“The scientific community’s work is irrelevant to what goes on here,” he told The New York Times Magazine in 2000. “The rehabilitation of head-injured individuals is a clinical, creative endeavor. Can you really say how this blob of Jell-O creates all this wonderful feeling and thinking? No. The question really is, Can you reconstruct Humpty Dumpty after he has been shattered to pieces?”The process isn’t easy, or cheap. Dr. Ben-Yishay’s 20-week program involves daylong sessions, often in small groups, and costs about $60,000. Yet it has become the gold standard for treating brain injuries, inspiring similar programs worldwide.“I was giving a talk about my program in Amsterdam,” said Keith Cicerone, the retired director of cognitive rehabilitation at the JFK Medical Center in New Jersey. “Afterward, several people from around the world came up to me and said how similar their programs were. Pretty soon we realized that we had copied from Yehuda.”Yehuda Ben-Yishay was born on Feb. 11, 1933, in Cluj, a city in the Transylvania region of western Romania. His father, Chaim Ben-Yishay, was a businessman; his mother, Leah (Finkelstein) Ben-Yishay, was a seamstress.His family went through World War II largely unscathed. Though hundreds of thousands of fellow Romanian Jews died during the Holocaust, hundreds of thousands survived, especially those in the southern reaches of Transylvania, where the family had moved shortly before the war.The Ben-Yishays were eager Zionists, and in 1946 they boarded a converted cattle ship with about 2,000 other Jews bound for Palestine. The British authorities had banned such mass migration, and on arrival Yehuda he and his two brothers and sister were separated from their parents as they were placed in refugee camps.After Israel’s independence in 1948, Dr. Ben-Yishay served in the Nahal, a part of the Israel Defense Force that built agricultural settlements. He later attended Hebrew University in Jerusalem, hoping to study psychology, but there was no one to teach it: Arab guerrillas had murdered the head of the department and several colleagues in 1948.Dr. Ben-Yishay studied sociology instead, graduating in 1957. He won a scholarship to the New School for Social Research in Manhattan and arrived at the end of that year.To cover his living expenses, he taught Hebrew and worked with retirees, including at a summer camp in Brewster, N.Y. There he met Myrna Pitterman; they married in 1960 and had three sons, Ari, Ron and Seth. All survive him along with his brothers, Yisrael and Meir; his sister, Pnina; and eight grandchildren.At the New School, Dr. Ben-Yishay fell under the guidance of a German émigré psychologist named Kurt Goldstein. Dr. Goldstein insisted that patients with traumatic injuries could recover only in a “holistic” environment, which would take into account not only their physical well-being but also their emotional and spiritual health.Dr. Ben-Yishay joined the Rusk Institute in 1964 and received his Ph.D. in psychology from N.Y.U. three years later. The institute’s founder, Howard A. Rusk, was himself a pioneer in physical rehabilitation, and like Dr. Goldstein he believed in a “whole patient” approach. (He was also a medical columnist for The New York Times.)Dr. Rusk encouraged Dr. Ben-Yishay and Dr. Diller, who ran the psychology department at Rusk, to apply that same approach to brain injuries, an increasingly urgent field. Thanks to improvements in automobile safety and battlefield medicine, more people were surviving accidents and combat incidents but with significant, if not always obvious, damage to their brains.Dr. Ben-Yishay confronted what was then considered a philosophical question: What is the nature of recovery? Is it strictly neurological, a result of biological changes in the brain? Or is it also behavioral, psychological, a result of learning and outside intervention by doctors, friends and family?Most researchers assumed it was the former, and that little could be done, aside from isolated efforts to make life easier for patients whom they thought were destined to live a life of mental anguish. Dr. Ben-Yishay thought otherwise, that cognition — things like memory, attention, reasoning — could be relearned or strengthened after a brain injury, and he spent the better part of the 1970s developing his approach.Though he faced significant skepticism at first, his program showed results. Before he began, only about 20 percent of patients with traumatic brain injuries were able to go back to work in some capacity; about two-thirds of patients who worked with Dr. Ben-Yishay and his team could do so, he estimated.Dr. Ben-Yishay was always quick to note the limits to his program. He was not there to cure a patient; no one could.“Once brain-injured, you are always brain-injured, for the rest of your life,” he told The Times in 2006.What he could do, though, was help patients develop ways to compensate, which began with recognizing what had happened to them and committing to the hard work of building a new life. He used words like persistence and courage to describe the key to success in his program, and he helped his patients unlock those qualities within themselves.“If you are a sourpuss,” he liked to say, “you are not rehabilitated.”

Tick-borne encephalitis is a disease just as nasty as it sounds. Once bitten by an infected tick, some people develop flu-like symptoms that resolve quietly but leave behind rampant neurological disease — brain swelling, memory loss, and cognitive decline. Cases are on the rise in Central Europe and Russia with some 10,000 incidents reported each year. Vaccines can provide protection, but only for a limited time. There is no cure.
Now a new study describes antibodies capable of neutralizing the virus transmitted by tick bites. These so-called broadly neutralizing antibodies have shown promise in preventing TBE in mice and could inform the development of better vaccines for humans. Further, preliminary results suggest that the antibodies may not only prevent tick-borne encephalitis but even treat the condition, as well as the related Powassan virus emerging in the United States.
Lead author Marianna Agudelo and colleagues in the laboratory of Rockefeller’s Michel C. Nussenzweig examined nearly 800 antibodies obtained from individuals who had recovered from TBE or had been vaccinated to prevent infection. The most potent antibodies, designated VH3-48, turned out to be best suited to fend off future infections. They found that VH3-48 neutralized lab-grown varieties of the TBE virus, as well other tick-borne illnesses including the Langat, Louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses.
The researchers also showed that these powerful antibodies are not common; in fact, most of the antibodies produced by humans exposed to TBE virus are of inferior quality, with the coveted VH3-48 antibodies making only occasional appearances. Moreover, vaccinated patients in the study did not manage to develop any VH3-48 antibodies at all. “You’d expect the most prevalent antibodies to be the absolute best, but that is not what we found in TBE,” Agudelo says. “This may explain how the virus tricks the immune system, misdirecting it into producing inferior antibodies.”
The discovery of VH3-48 provides hope for a more effective TBE vaccine. Current vaccines require three doses spaced over two years and only provide about five years of protection before a booster shot is required. Next-generation vaccines built around coaxing the body into producing the rare VH3-48 antibody could be more potent, require fewer booster shots, and also prove protective against a number of tick-borne viruses.
“A vaccine like this would not just be more elegant, but also better focused,” says Michel C. Nussenzweig, the Zanvil A. Cohn and Ralph M. Steinman Professor and head of the Laboratory of Molecular Immunology at Rockefeller. “Now that we have the structures of these antibodies, we know what to target in order to design more effective vaccines.”
Broadly neutralizing antibodies may also provide the first specific treatment for TBE. Nussenzweig, Agudelo, and colleagues found that mice infected with TBE recover after receiving antibody therapy, although it remains to be seen if this finding will translate to humans.
“The next step is a clinical trial with the antibodies,” Nussenzweig says, “perhaps in Europe where there are many cases, to see whether we can ameliorate the symptoms of those suffering from encephalitis.”
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New studies from Germany and Norway examined cases involving mostly younger people who developed serious and sometimes fatal blood disorders.Two reports published on Friday in a leading medical journal help to explain how AstraZeneca’s Covid vaccine can, in rare cases, cause serious and sometimes fatal blood clots.Scientific teams from Germany and Norway found that people who developed the clots after vaccination had produced antibodies that activated their platelets, a blood component involved in clotting. The new reports add extensive details to what the researchers have already stated publicly about the blood disorder.Why the rare reaction occurred is not known. Younger people appear more susceptible than older ones, but researchers say no pre-existing health conditions are known to predispose people to the problem, so there is no way to tell if an individual is at high risk.Reports of the clots have already led a number of countries to limit AstraZeneca’s vaccine to older people, or to stop using it entirely. The cases have dealt a crushing blow to global efforts to halt the pandemic, because the AstraZeneca shot — easy to store and relatively cheap — has been a mainstay of vaccination programs in more than 100 countries.Regulators in Europe have emphasized that the clotting disorder is rare, and that the vaccine’s benefits far outweigh its risks. But when a side effect has the potential to be devastating or fatal — like the blood clots in the brain linked to this vaccine — some regulators and segments of the public find the risk unacceptable, even if it is extremely rare.As of Sunday, European regulators had received reports of 222 cases of the rare blood-clotting problem in Britain and the 30-nation European Economic Area (the European Union plus Iceland, Norway and Liechtenstein). They said that about 34 million people had received the AstraZeneca vaccine in those countries, and that the clotting problems were appearing at a rate of about one in 100,000 recipients.European regulators said that as of March 22, they had carried out detailed reviews of 86 cases, 18 of which had been fatal.The safety bar for vaccines is set high, because they are given to healthy people. The seemingly greater vulnerability of younger people to the clotting disorder is of particular concern, because their risk of severe illness from Covid itself is lower than that in older people. Those differences suggest that overall, compared to older people, younger people may have less to gain and more to lose from the AstraZeneca vaccine.Doses of the Astra Zeneca vaccine, which is easy to store and relatively inexpensive, in a refrigerator in St. Mary’s Hospital in Dublin.Clodagh Kilcoyne/ReutersGermany, the Netherlands, the Philippines, Portugal and Spain have recommended that the AstraZeneca vaccine be given only to people over 60. Canada and France have limited it to those over 55; Australia, over 50; Belgium, over 56. Britain, where the vaccine was developed, has been its staunchest defender, but announced on Wednesday that it would begin offering alternative shots to people under 30.Cameroon, the Democratic Republic of Congo, Denmark and Norway have stopped using the vaccine.Full vaccination with the AstraZeneca vaccine requires two doses, but regulators in France have recommended that people under 55 who have had one dose get a different vaccine for their second shot.The AstraZeneca vaccine is not authorized for use in the United States, but the Food and Drug Administration is reviewing data on it to determine whether it should be.On Wednesday, the European Medicines Agency said that the vaccine’s labeling should be revised to include listing the clotting disorder as a “very rare” side effect of the vaccine.In a statement on its website, AstraZeneca said it was “actively collaborating with the regulators to implement these changes to the product information and is already working to understand the individual cases, epidemiology and possible mechanisms that could explain these extremely rare events.”The two new reports were published by The New England Journal of Medicine. One from Germany describes 11 patients, including nine women ages 22 to 49. Five to 16 days after vaccination, they were found to have one or more clots. Nine had cerebral venous thrombosis, a clot blocking a vein that drains blood from the brain. Some had clots in their lungs, abdomen or other areas. Six of the 11 died, one from a brain hemorrhage.One patient had pre-existing conditions that affected clotting, but during a news briefing on Friday, Dr. Andreas Greinacher, an author of the report, said those conditions most likely played only a minor role in the disorder that occurred after vaccination.All the patients, as well as 17 others with clots after vaccination whose blood was tested, had antibodies known to activate platelets.The antibodies led to a condition called thrombotic thrombocytopenia, which causes both clotting and abnormal bleeding. The researchers suggested naming the newly identified version in these patients “vaccine-induced immune thrombotic thrombocytopenia.”The article described specialized blood tests that can be used to diagnose the disorder, and suggested treatment with a blood product called intravenous immune globulin, which is used to treat various immune disorders. Drugs called anti-coagulants, or blood thinners, can also be administered in some cases, but not a commonly used one, heparin — because the vaccine-related condition is very similar to one that occurs, rarely, in people given heparin.The second report, from Norway, described five patients, one male and four female health care workers ages 32 to 54, who had clots and bleeding from seven to 10 days after receiving the AstraZeneca vaccine. Four had severe clots in the brain, and three died. Severe headaches were among their early symptoms. Like the German patients, all had high levels of antibodies that could activate platelets.The team from Norway also recommended treatment with intravenous immune globulin. The researchers said the disorder was rare, but “a new phenomenon with devastating effects for otherwise healthy young adults,” and they suggested that it may be more common than previous studies of the AstraZeneca vaccine had indicated.On Friday, European regulators also said they were reviewing reports of a few blood clot cases that occurred in people who had received the Johnson and Johnson vaccine. In the United States, federal agencies are investigating reports of a different type of unusual blood disorder involving a precipitous drop in platelets that emerged in a few people who had received either the Pfizer-BioNTech or Moderna vaccines.Benjamin Mueller and Melissa Eddy contributed.

A new study using human genetics suggests researchers should prioritize clinical trials of drugs that target two proteins to manage COVID-19 in its early stages.
The findings appeared online in the journal Nature Medicine in March 2021.
Based on their analyses, the researchers are calling for prioritizing clinical trials of drugs targeting the proteins IFNAR2 and ACE2. The goal is to identify existing drugs, either FDA-approved or in clinical development for other conditions, that can be repurposed for the early management of COVID-19. Doing so, they say, will help keep people with the virus from being hospitalized.
IFNAR2 is the target for approved drugs often used by patients with relapsing forms of the central nervous system disorder multiple sclerosis. The researchers believe the most promising ACE2 therapy against COVID-19 is a drug that was developed before the pandemic began and has been evaluated in clinical trials to reduce inflammatory response in patients with severe respiratory disorders.
Dr. Juan P. Casas, a physician epidemiologist at the Veterans Affairs Boston Healthcare System, led the study. The research included collaborators from the University of Cambridge and the European Bioinformatics Institute in England, and Istituto Italiano di Tecnologia in Italy.
“When we started this project early last summer, most COVID-19 trials were being done on hospitalized patients,” Casas explains. “Very few treatments were being tested to give to patients early in the natural history of the disease. However, as the availability of testing against coronavirus increased, an opportunity opened to identify and treat COVID-19 patients before they progress to more severe forms that require hospitalization.

A tiny protein of SARS-CoV-2, the coronavirus that gives rise to COVID-19, may have big implications for future treatments, according to a team of Penn State researchers.
Using a novel toolkit of approaches, the scientists uncovered the first full structure of the Nucleocapsid (N) protein and discovered how antibodies from COVID-19 patients interact with that protein. They also determined that the structure appears similar across many coronaviruses, including recent COVID-19 variants — making it an ideal target for advanced treatments and vaccines. They reported their results in Nanoscale.
“We discovered new features about the N protein structure that could have large implications in antibody testing and the long-term effects of all SARS-related pandemic viruses,” said Deb Kelly, professor of biomedical engineering (BME), Huck Chair in Molecular Biophysics and director of the Penn State Center for Structural Oncology, who led the research. “Since it appears that the N protein is conserved across the variants of SARS-CoV-2 and SARS-CoV-1, therapeutics designed to target the N protein could potentially help knock out the harsher or lasting symptoms some people experience.”
Most of the diagnostic tests and available vaccines for COVID-19 were designed based on a larger SARS-CoV-2 protein — the Spike protein — where the virus attaches to healthy cells to begin the invasion process.
The Pfizer/BioNTech and Moderna vaccines were designed to help recipients produce antibodies that protect against the Spike protein. However, Kelly said, the Spike protein can easily mutate, resulting in the variants that have emerged in the United Kingdom, South Africa, Brazil and across the United States.
Unlike the outer Spike protein, the N protein is encased in the virus, protected from environmental pressures that cause the Spike protein to change. In the blood, however, the N protein floats freely after it is released from infected cells. The free-roaming protein causes a strong immune response, leading to the production of protective antibodies. Most antibody-testing kits look for the N protein to determine if a person was previously infected with the virus — as opposed to diagnostic tests that look for the Spike protein to determine if a person is currently infected.

A new study published in the Journal of Alzheimer’s Disease Reports continues to support a growing body of evidence that aluminum contributes to the pathogenesis of Alzheimer’s disease (AD). Researchers found aluminum co-located with phosphorylated tau protein, which is an early initiator of AD. This study builds upon two earlier published studies (including Mold et al., 2020, Journal of Alzheimer’s Disease) from the same group.
The new data demonstrate that aluminum is co-located with phosphorylated tau protein, present as tangles within neurons in the brains of early-onset or familial Alzheimer’s disease. “The presence of these tangles is associated with neuronal cell death, and observations of aluminum in these tangles may highlight a role for aluminum in their formation,” explained lead investigator Matthew John Mold, PhD, Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, UK.
The earlier research highlighted widespread co-localization of aluminum and amyloid-β in brain tissue in familial AD. The researchers used a highly-selective method of immunolabelling in the current study, combined with aluminum-specific fluorescence microscopy. Phosphorylated tau in tangles co-located with aluminum in the brain tissue of the same cohort of Colombian donors with familial AD were identified. “It is of interest and perhaps significance with respect to aluminum’s role in AD that its unequivocal association with tau is not as easily recognizable as with amyloid-β. There are many more aggregates of aluminum with amyloid-β than with tau in these tissues and the latter are predominantly intracellular,” remarked co-author, Professor Christopher Exley.
George Perry, PhD, Editor-in-Chief of the Journal of Alzheimer’s Disease, comments: “Aluminum accumulation has been associated with Alzheimer’s disease for nearly half a century, but it is the meticulously specific studies of Drs. Mold and Exley that are defining the exact molecular interaction of aluminum and other multivalent metals that may be critical to formation of the pathology of Alzheimer’s disease.”
“The new data may suggest that the association of aluminum with extracellular senile plaques precedes that with intracellular aggregates of tau. These relationships with both amyloid-β and tau may account for the high levels of aluminum observed in the brain tissue of donors with familial AD versus those without a diagnosis of neurodegenerative disease,” said Dr. Mold. “Tau and amyloid-beta are known to act in synergy to produce neurotoxicity in AD and our data provide new evidence for a role of aluminum in this process.”
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Psychosocial stress — typically resulting from difficulty coping with challenging environments — may work synergistically to put women at significantly higher risk of developing coronary heart disease, according to a study by researchers at Drexel University’s Dornsife School of Public Health, recently published in the Journal of the American Heart Association.
The study specifically suggests that the effects of job strain and social strain — the negative aspect of social relationships — on women is a powerful one-two punch. Together they are associated with a 21% higher risk of developing coronary heart disease. Job strain occurs when a woman has inadequate power in the workplace to respond to the job’s demands and expectations.
The study also found that high-stress life events, such as a spouse’s death, divorce/separation or physical or verbal abuse, as well as social strain, were each independently linked with a 12% and 9% higher risk of coronary heart disease, respectively.
The Drexel study used data from a nationally representative sample of 80,825 postmenopausal women from the Women’s Health Initiative Observational Study, which tracked participants from 1991 to 2015, to find better methods of preventing cancer, heart disease and osteoporosis in women. In the current follow-up study, Drexel researchers evaluated the effect of psychosocial stress from job strain, stressful life events and social strain (through a survey), and associations among these forms of stress, on coronary heart disease.
Nearly 5% of the women developed coronary heart disease during the 14-year, seven-month study. Adjusting for age, time at a job, and socioeconomic characteristics, high-stress life events were associated with a 12% increased coronary heart disease risk, and high social strain was associated with a 9% increased risk of coronary heart disease. Work strain was not independently associated with coronary heart disease.
Coronary heart disease, the leading cause of death in the United States, occurs with the heart’s arteries become narrow and cannot bring sufficient oxygenated blood to the heart. The latest work builds on earlier studies linking psychosocial stress to coronary heart disease by finding out how job strain and social strain work together to compound disease risk.
“The COVID-19 pandemic has highlighted ongoing stresses for women in balancing paid work and social stressors. We know from other studies that work strain may play a role in developing CHD, but now we can better pinpoint the combined impact of stress at work and at home on these poor health outcomes,” said senior author Yvonne Michael, ScD, SM, an associate professor in the Dornsife School of Public Health. “My hope is that these findings are a call for better methods of monitoring stress in the workplace and remind us of the dual-burden working women face as a result of their unpaid work as caregivers at home .”
The study’s authors say that future studies should look at the effects of shift work on coronary heart disease and explore the effects of job demands according to gender.
“Our findings are a critical reminder to women, and those who care about them, that the threat of stress to human health should not go ignored,” said lead author Conglong Wang, PhD, a recent Dornsife graduate who conducted the research while at Drexel. “This is particularly pertinent during the stressors caused by a pandemic.”
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A new biosealant therapy may help to stabilize injuries that cause cartilage to break down, paving the way for a future fix or — even better — begin working right away with new cells to enhance healing, according to a new animal-based study by researchers at the Perelman School of Medicine at the University of Pennsylvania. Their research was published in Advanced Healthcare Materials.
“Our research shows that using our hyaluronic acid hydrogel system at least temporarily stops cartilage degeneration that commonly occurs after injury and causes pain in joints,” said the study’s senior author, Robert Mauck, PhD, a professor of Orthopaedic Surgery and the director of Penn Medicine’s McKay Orthopaedic Research Laboratory. “In addition to pausing cartilage breakdown, we think that applying this therapy can present a surface that is ‘sticky’ for cells, such as stem cells that are routinely injected into joints to counteract injury. This reinforcing hydrogel could actually synergize with those cells to create a long-term solution.”
Articular cartilage is the tissue that covers the ends of bones at joints. It keeps bones from painfully grinding together, and its density and resilience allow it to undergo a lot of forces amid human movement. Unfortunately, these routine yet complex stresses cause cartilage to wear down easily — particularly amid some form of injury — and is hard to replace or regrow. This means that it is especially important to keep the remaining cartilage strong and stable.
To that end, Mauck, study lead author Jay Patel, PhD, a former post-doctoral fellow in the McKay Lab and now assistant professor at Emory University, and their team developed a therapy to use a modified version of hyaluronic acid — a substance naturally produced by the body’s connective tissue — that could be introduced to the injured cartilage site. They recognized that this therapy needed to follow a twofold key to preserving cartilage: reinforcement and sealing.
“We often relate this combined approach to treating a damaged deck in your backyard,” Patel said. “To fortify the existing wood structure, you need something like a wood hardener, then you can apply a wood sealer to prevent future wear. In the same way, we applied a substance that seeps into the pores of the tissue and provides reinforcement, then ‘sealed’ it by guiding the behavior of injected stem cells towards forming a layer that caps the whole structure.”
In a large animal model, the researchers introduced the biogel to damaged cartilage, showing that it intertwined with the cartilage’s matrix structure to stabilize the cartilage. They also demonstrated that it was retained for at least one week in the joint environment. When living cartilage was tested in the lab, the researchers found that applying the hyaluronic acid biogel restored regular activity to chondrocytes, the cells within cartilage tissue. This meant that the microenvironment around the cells was now being reinforced.
Once reinforced, the researchers shifted to sealing the cartilage, so that further tissue loss at the injury site didn’t erode the cartilage’s structure. To that end, the team combined the hyaluronic acid hydrogel system with an injection of mesenchymal stem/stromal cells, to promote the formation of a thin “living” barrier on the cartilage surface to protect it from further wear. When the researchers compared models that received the treatment to ones that did not, the treatment models displayed a thicker layer of protective tissue that could protect the cartilage’s structure and preserve function.
“We’ve shown that this is an innovative technology and methodology for potentially addressing the complexities of treating damaged cartilage tissue that traditionally have made it so difficult,” said Patel. “Next, we hope to translate this technology to more large animal studies and to the clinic in the near future.”
These findings led to a translational grant from Penn Health Tech, the interdisciplinary center that combines teams from Penn Medicine and Penn Engineering to create new medical technology. Further, the technology is at the heart of a new company (Forsagen LLC) spun out of Penn with support from the Penn Center for Innovation (PCI) Ventures Program, which will attempt to spearhead the system’s entry into the clinic. It is co-founded by both Mauck and Patel, along with study co-author Jason Burdick, a professor of Bioengineering at Penn, and Ana Peredo, a PhD student in Bioengineering.
Note: Mauck, Patel, and Burdick are equity holders, along with Penn, are equity holders in Forsagen LLC. They also stand to receive financial considerations from future commercialization of the technology.

The concept of documenting vaccinations is being taken to new levels of sophistication, and experts predict that electronic verification will soon become commonplace.With Covid-19 vaccinations accelerating, attention is turning to tools for people to prove that they have been inoculated and potentially bypass the suffocating restrictions used to fight the pandemic.Though the idea is meeting some resistance over privacy and equity concerns, several types of coronavirus vaccination records, sometimes called “vaccine passports,” already exist, in paper and digital form. Hundreds of airlines, governments and other organizations are experimenting with new, electronic versions, and the number grows daily, although so far their use has been very limited.Portable vaccine records are an old idea: Travelers to many parts of the world, children enrolling in school and some health care workers have long had to supply them as proof that they have been vaccinated against diseases.But vaccine passports use digital tools that take the concept to new levels of sophistication, and experts predict that electronic verification will soon become commonplace, particularly for international air travel, but also for admission to crowded spaces like theaters.Here are some of the main questions being asked.What is a “vaccine passport?”Generally, people are using the term to mean an electronic record of vaccination, possibly in the form of a QR code, that is easily accessible through a smartphone or possibly stored on the device, though it could also be printed out.At its simplest, documentation is something like the physical card created by the Centers for Disease Control and Prevention and usually given to people when they receive their first Covid-19 shot in the United States, or the World Health Organization’s “yellow card,” used for decades by travelers to show inoculation against diseases like yellow fever. But those are on paper, filled out by hand and fairly vulnerable to forgery.The tool might have to address several variables: It is unclear how long inoculation lasts, there can be bad batches and the emergence of new variants of the virus are likely to require new vaccines. So in the long run, an electronic record might need to show which specific vaccine a person received, from which batch and when.More than a dozen competing versions are already being developed and promoted.Handing out a vaccination document after giving a vaccine to a patient in Budapest, Hungary, last month.Akos Stiller for The New York TimesHow would it be used?In the short run, the clearest application may be in international travel, and the reason is evident at any major airport: Passenger volume is at a fraction of prepandemic levels, yet there are enormous lines at airline counters and passport control.Many countries already require proof of a recent, negative coronavirus test for entry. So far, that documentation has existed almost entirely on paper or on passenger’s phone, and must be confirmed by human eyes at the airport, so checking in for a flight online, or even at an electronic kiosk in the terminal, is out.As travel restrictions ease, volume will increase, and many nations are expected to begin requiring proof of vaccination (or prior coronavirus infection) to enter, or just to skip the quarantine requirement. More passengers and more documentation requirements will make processing even more unwieldy.“We have to automate this thing,” said Nick Careen, senior vice president of the International Air Transport Association, an airline industry trade group. “Even if there is never a vaccination requirement approved, there is still going to be a requirement for testing, and we can’t do this manually.”(Even with an electronic system, officials say, there will be some people who must use paper health documents because they lack access to digital tools.)No major country has publicly floated vaccine verification for domestic travel. But some governments and businesses already require proof of a negative coronavirus test for entry to certain crowded locations, and a few have started demanding proof of vaccination, increasing the desire for an electronic alternative.To be most useful, a digital record would have to be widely adopted — by governments checking travelers, by airlines and ship lines screening passengers, by businesses restricting admission and by the hodgepodge of health care providers, government agencies and pharmacies that are giving the shots.That, in turn, means it would have to be easy to use, and relatively inexpensive. Requiring organizations to spend a lot of money or adopt new software would be a barrier.Passengers in the departure lobby of Haneda airport in Tokyo. Japan, like other Asian countries, has curbed the virus mainly through strict border controls.James Matsumoto/SOPA Images, via Getty ImagesWho is using it?In February, Israel’s government began issuing its digital Green Pass or a physical certificate to people who had been vaccinated, and it is required to enter places like hotels and theaters.In the past month, hundreds more entities around the world — airlines, governments, drugstore chains and others — began using privately controlled digital systems to verify health credentials. Most are using the systems — including one called CommonPass and the International Air Transport Association’s own system, Travel Pass — on a trial basis, to verify negative coronavirus tests.The systems are designed to show proof of vaccination, as well, if that is required.In March, Aruba and JetBlue began allowing passengers from the United States to show a negative test using CommonPass, developed by the Commons Project, a Swiss-based nonprofit, with support from the World Economic Forum. Lufthansa passengers flying into the United States can also use it.The same month, Singapore Airlines became the first carrier to make limited use of Travel Pass for people flying between Singapore and London, and will put it into wide use in May.Also in March, New York State became the first government in the United States to implement a system, the Excelsior Pass, developed with IBM, which some venues have used to prove vaccination. The governors of Florida and Texas have vowed to block any such system in their states, calling it government overreach and an invasion of privacy.Iceland this month eased entry restrictions for people who have been vaccinated, and Britain is about to start experimenting with a vaccine verification requirement to attend sporting events, though so far neither country has adopted a digital system.The Biden administration acknowledges that private entities will use such systems, but says the federal government will not be involved in creating one. “There will be no federal vaccinations database and no federal mandate requiring everyone to obtain a single vaccination credential,” Jen Psaki, the White House press secretary, said this week.That does not, however, rule out a federal agency using a privately developed electronic health credential to screen international travelers.An Israeli woman showing her Green Pass before entering a show at an opera house in Tel Aviv.Dan Balilty for The New York TimesWhat are the obstacles and objections?Many of the objections that have been raised are about privacy, but people developing the systems say those can be addressed.CommonPass and its app, for example, do not hold any of the user’s health records, said Paul Meyer, chief executive of the Commons Project Foundation. If a participating airline needs to know whether a passenger has had a negative test or inoculation, and a participating pharmacy has the information, CommonPass can communicate with both and return a simple yes or no answer, without transmitting any specific data.“You shouldn’t have to hand over your health record to Yankee Stadium or an airline,” Mr. Meyer said.Many technology and health care entities have banded together as the Vaccine Credential Initiative, to develop a broadly agreed-upon set of open standards, meaning that the software underlying a verification system is transparent and it can adapt easily to other systems, while safeguarding privacy. The W.H.O. has a similar initiative, the Smart Vaccination Certificate.But several companies are creating closed, proprietary systems that they hope to sell to clients, and some apparently would have access to users’ information.One concern is that a profusion of systems might not be compatible, defeating the purpose of making it easy to check someone’s status.Another objection is that any requirement to prove vaccination status would discriminate against those who can’t get the shot or refuse to, and there is lingering uncertainty about how well inoculation prevents virus transmission.For those reasons, the W.H.O. said this week that it does not support requiring proof of vaccination for travel — for now.