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Friday, September 3, 2021

Florida may consider abortion bill similar to Texas after SCOTUS decision

 Florida may consider adopting an abortion ban similar to that of Texas, which banned all abortions after a fetal heartbeat can be detected —  around six weeks after conception —  after the Supreme Court declined to hear the case on Wednesday.

Republican Florida Senate President Wilton Simpson confirmed that the Sunshine State would be likely joining other states in passing anti-abortion legislation following the Supreme Court’s decision, he told WFLA on Thursday.

“When the Supreme Court goes out and makes a decision like this, it clearly is going to send a signal to all the states that are interested in banning abortions or making it more restrictive to have an abortion in their state, it’s certainly going to make us take a look at those issues,” Simpson said.

The US Supreme Court voted 5-4 on Wednesday denying an emergency appeal filed by abortion providers in an attempt to block a Texas abortion bill that went into effect the same day. 

Signed by Texas Gov. Greg Abbott in May, the new law prohibits women from getting an abortion after a fetal heartbeat can be detected, roughly around six weeks and before most women know they are pregnant.

The controversial law does not make exceptions for rape or incest survivors.

Florida State Senator Annette Taddeo of Miami-Dade County says this law violates women’s privacy rights

“Understand what Florida Republicans want to do: They want to give rapists the right to sue their victims to stop them from getting an abortion – and to be able to collect money from their victims who try to have an abortion,” Democratic Florida state senator Annette Taddeo said in a statement to NBC6. “If Republicans get their way, rapists will have more power over this decision than the victim.”

The Texas bill also includes unique authority for private citizens to sue abortion providers and anyone involved in facilitating abortions — such as driving a woman to a clinic — for at least $19,000, if successful.

Florida Gov. Ron DeSantis said on Thursday he supports pro-life legislation and wiould be looking into it.

“What they did in Texas was interesting, and I haven’t really been able to look enough about it, they’ve basically done this through private right of action, so it’s a little bit different than how a lot of these debates have gone, so we’ll have to look, I’m going to look more significantly at it,” DeSantis said, according to NBC6. “I do think that at the end of the day the science on this has been very powerful now for a long time, you go back 40 years ago what people thought versus what they can see now, very very powerful, so I’ve always been somebody that really does support protections for life, as best as we can do.”

https://nypost.com/2021/09/02/florida-may-consider-abortion-bill-similar-to-texas/

Fauci says new COVID variant called Mu not ‘immediate threat’ to US

 Dr. Anthony Fauci on Thursday said that the new Mu variant of COVID-19 is not considered to be “an immediate threat” to the US.

Federal officials are “keeping a very close eye” on the virus mutation, though its “not at all even close to being dominant” in the US, the White House chief medical advisor said.

“Bottom line, we’re paying attention to it. We take everything like that seriously, but we don’t consider it an immediate threat right now,” Fauci said during a White House COVID-19 briefing.

Also known as B.1.621, the strain was added to the World Health Organization’s “variant of interest” list on Monday. Preliminary data shows it may evade certain antibodies, meaning vaccines would be less effective against it, but experts said more research on the strain is necessary.

Since first emerging in Colombia in January, the variant has popped up in at least 39 countries, including in the US.

But Fauci said Mu has not yet “taken hold” in the country, where the Delta variant is dominant by far, accounting for about 99 percent of new cases.

The 7-day rolling average of new COVID-19 cases was nearly 150,000 per day, while hospitalizations were at 12,000 and deaths at 953, according to Centers for Disease Control and Prevention director Dr. Rochelle Walensky.

The CDC head also announced the agency would publish two new studies on Friday about COVID-19 in children, showing that kids who live in communities with high vaccination rates had lower chances of becoming hospitalized with COVID-19.

The findings previewed by Walensky also showed that the rate at which kids were hospitalized with COVID-19 was nearly four times higher in states that had the lowest overall vaccination rates.

These studies demonstrated that there was not increased disease severity in children. Instead, more children have COVID-19 because there is more disease in the community,” she said.

At least 175 million Americans are now fully vaccinated against the virus, up 10 million from a month ago, officials said at the briefing.

The US saw an uptick in inoculations following the full approval of the Pfizer-BioNTech vaccine by the Food and Drug Administration last month, but the increase could also be due to other factors, including fear of the Delta variant.

Fauci also told reporters its “likely” that Americans will eventually need to get a third dose of the vaccine to be considered fully inoculated, though a final determination would be made by the FDA and the CDC.

He discussed data from studies conducted on Israel’s booster shot rollout which showed the risk of COVID-19 infection was lower in people who had received a third dose of the vaccine.

White House COVID-19 coordinator Jeff Zients said the federal government will bring the “same intensity” to encouraging Americans to get booster shots as it did for the initial vaccination campaign.

Zients also announced the US would invest another $3 million to expand production of “critical supplies,” including vaccines in US companies.

The US has committed to donating 600 million doses of the shot to other nations, Zients said, “far and away the largest contribution made by any country.”

“We can protect the American people, and contribute to the world as we are leading the world in vaccine doses donated,” he told reporters.

https://nypost.com/2021/09/02/fauci-says-new-covid-variant-called-mu-not-immediate-threat-to-us/

Evidence mounts that MMR, Tdap vaccines strengthen protection against severe COVID-19

 Vaccines are designed to induce a strong and long-lasting immune response through the creation of memory T cells and B cells. The Measles-Mumps-Rubella (MMR) vaccine, given during early childhood, and Tetanus-Diphtheria-Pertussis (Tdap) vaccine, given every 10 years, are known to elicit a protective response against the diseases from which the vaccines get their names. But these vaccines may have an unexpected bonus: It's possible that they also elicit cross-reactive memory T cells capable of responding to protein targets called antigens that are present in other microbes that cause diseases -- including the viral antigens in SARS-CoV-2. The concept is that pre-existing memory T cells generated by prior MMR or Tdap vaccination and activated by SARS-CoV-2 infection give the immune system a head start in responding to SARS-CoV-2, thereby lowering the risk of severe COVID-19.

To investigate whether the MMR and Tdap vaccines provide additional protection against COVID-19, researchers at Brigham and Women's Hospital conducted laboratory-based analyses using sensitive, new techniques to detect and characterize T cell responses to antigens. They applied these techniques to measure the response of T cells isolated from the blood of COVID-19 convalescent patients and patients vaccinated against COVID-19 to antigens from SARS-CoV-2 and the MMR and Tdap vaccines. Teaming up with collaborators at Cleveland Clinic, they also leveraged a large, well-annotated cohort of COVID-19 patients and found that prior MMR or Tdap vaccination was associated with decreased disease severity. Their results are published in Med.

"Our Cleveland Clinic colleagues observed an association where individuals with COVID-19 who had either MMR or Tdap vaccines had a much lower frequency of going to the intensive care unit or dying," said co-author Andrew Lichtman, MD, PhD, an immunologist and senior investigator in the Brigham's Department of Pathology and professor of Pathology at Harvard Medical School. "Although previous smaller studies suggested a similar link, our in-depth epidemiological analyses, together with our basic research results, suggest that these commonly given vaccines may protect against severe disease."

"During the COVID-19 pandemic, we know that there was a marked decline in routine vaccinations for children and adolescents," said corresponding author Tanya Mayadas, PhD, a senior scientist in the Brigham's Department of Pathology and professor of Pathology at Harvard Medical School. "Our findings emphasize the importance of routine vaccination for children and adults. We know vaccines protect against devastating diseases, and we're now seeing growing evidence that some of them provide a degree of protection against severe COVID-19 disease."

The team's investigation was jumpstarted by an unexpected observation. Mayadas, her postdoctoral fellow Vijaya Mysore, PhD, and colleagues noted in laboratory experiments using COVID-19 convalescent blood that whenever they observed a heightened T cell response to SARS-CoV-2 proteins, they also saw a heightened response to proteins from MMR and Tdap, which they had been using as controls. This was observed with both COVID-19 convalescent and uninfected individuals vaccinated against SARS-CoV-2. This connection was made by the team's use of highly efficient antigen-presenting cells (described in a recently published Nature Communications paper) derived from blood, loaded with SARS-CoV-2, MMR or Tdap antigens, and co-cultured with T cells from the same individual. Using single-cell RNA sequencing and analysis of T cell antigen receptors, the team observed that the antigen receptors on many of the T cells from individuals who had recovered from COVID-19 that responded to proteins from SARS-CoV-2 (Spike-S1 and Nucleocapsid) were identical to the antigen receptors on T cells that responded to MMR and Tdap proteins. This discovery indicated the presence of T cell clones that can respond to both SARS-CoV-2 antigens and the MMR and Tdap vaccine antigens.

In a second analysis, Mayadas and colleagues teamed up with investigators at Cleveland Clinic to examine the epidemiological evidence. The Cleveland Clinic team performed a retrospective cohort study using data from more than 75,000 patients seen at the Cleveland Clinic Health System in Ohio or Florida who had tested positive for COVID-19 between March 8, 2020, and March 31, 2021. The team used a statistical method known as overlap propensity score weighting to compare two disease severity outcomes (COVID-related hospitalization and COVID-related admission to the intensive care unit or death) for patients who had been vaccinated against MMR or Tdap and those who had not. They found that patients who had previously been vaccinated for MMR had a 38 percent decrease in hospitalization and a 32 percent decrease in ICU admission/death. Similarly, patients previously vaccinated for Tdap had 23 percent and 20 percent decreased rates, respectively, of these outcomes.

"Beyond learning about the potential benefits of the MMR and Tdap vaccines in the context of COVID-19, this study provides a blueprint for accelerating research," said co-author Lara Jehi, MD, MHCDS, Chief Research Information Officer of the Cleveland Clinic Health System. "Biomedical hypotheses generated in the laboratory can be explored through robust clinical and epidemiological research in well-curated, real-world data such as the Cleveland Clinic COVID Registry. Knowledge learned through this collaboration is much more than the sum of our individual parts."

The authors note that while their laboratory-based findings are strengthened by the epidemiological observations, further work is needed to assess the association between the MMR and Tdap vaccinations and severity of COVID-19 disease to determine if the relationship is a causal one. Prospective studies of vaccination and patient outcomes may help distinguish correlation from causation.

"With regards to COVID-19 vaccines, our findings predict that although MMR and Tdap are not a substitute for COVID-19 vaccines they may afford greater and more durable protection, possibly against emerging spike variants than the COVID-19 vaccine alone," said Mayadas. "And in areas where the COVID-19 vaccines are not available, they could protect infected individuals from developing severe disease."

Conflict of Interest: Co-author David R. Walt has a financial interest in Quanterix Corporation, a company that develops an ultra-sensitive digital immunoassay platform. He is an inventor of the Simoa technology, founder of the company and serves on its Board of Directors. The anti-SARS-CoV-2 Simoa assays in this publication have been licensed by Brigham and Women's Hospital to Quanterix Corporation. Co-author Tal Gilboa receives royalty payments from Brigham and Women's Hospital for the antibodies assay technology. Tanya Mayadas has a financial interest in neuAPC Therapeutics, a company that will develop anti-FcγRIIIB antibody for the generation of neutrophil-derived antigen presenting cells (nAPC) and serves as one of its scientific advisors. Co-authors Vijayashree Mysore, Xavier Cullere and Mayadas have a provisional patent on the generation of immunogenic nAPCs and methods of use thereof.

Funding: The work was supported by the National Institutes of Health R01HL065095, R01AI152522 and R01NS097719, a generous donation from Barbara and Amos Hostetter and the Chleck Foundation.


Story Source:

Materials provided by Brigham and Women's HospitalNote: Content may be edited for style and length.


Journal References:

  1. Vijayashree Mysore, Xavier Cullere, Matthew L. Settles, Xinge Ji, Michael W. Kattan, Michaël Desjardins, Blythe Durbin-Johnson, Tal Gilboa, Lindsey R. Baden, David R. Walt, Andrew H. Lichtman, Lara Jehi, Tanya N. Mayadas. Protective heterologous T cell immunity in COVID-19 induced by the trivalent Measles-Mumps-Rubella and Tetanus-Diptheria-Pertussis vaccine antigensMed, 2021; DOI: 10.1016/j.medj.2021.08.004
  2. Vijayashree Mysore, Xavier Cullere, Joseph Mears, Florencia Rosetti, Koshu Okubo, Pei X. Liew, Fan Zhang, Iris Madera-Salcedo, Frank Rosenbauer, Richard M. Stone, Jon C. Aster, Ulrich H. von Andrian, Andrew H. Lichtman, Soumya Raychaudhuri, Tanya N. Mayadas. FcγR engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunityNature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-24591-x

Comparing seniors who relocate long-distance shows where you live affects longevity

 Would you like to live longer? It turns out that where you live, not just how you live, can make a big difference.

That's the finding of an innovative study co-authored by an MIT economist, which examines senior citizens across the U.S. and concludes that some locations enhance longevity more than others, potentially for multiple reasons.

The results show that when a 65-year-old moves from a metro area in the 10th percentile, in terms of how much those areas enhance longevity, to a metro area the 90th percentile, it increases that person's life expectancy by 1.1 years. That is a notable boost, given that mean life expectancy for 65-year-olds in the U.S. is 83.3 years.

"There's a substantively important causal effect of where you live as an elderly adult on mortality and life expectancy across the United States," says Amy Finkelstein, a professor in MIT's Department of Economics and co-author of a newly published paper detailing the findings.

Researchers have long observed significant regional variation in life expectancy in the U.S., and often attributed it to "health capital" -- tendencies toward obesity, smoking, and related behavioral factors in the regional populations. But by analyzing the impact of moving, the current study can isolate and quantify the effect that the location itself has on residents.

As such, the research delivers important new information about large-scale drivers of U.S. health outcomes -- and raises the question of what it is about different places that affects the elderly's life expectancy. One clear possibility is the nature of available medical care. Other possible drivers of longevity include climate, pollution, crime, traffic safety, and more.

"We wanted to separate out the role of people's prior experiences and behaviors -- or health capital -- from the role of place or environment," Finkelstein says.

The paper, "Place-Based Drivers of Mortality: Evidence of Migration," is published in the August issue of the American Economic Review. The co-authors are Finkelstein, the John and Jennie S. MacDonald Professor of Economics at MIT, and Matthew Gentzkow and Heidi Williams, who are both professors of economics at Stanford University.

Comparing movers to see how place matters

To conduct the study, Finkelstein, Gentzkow, and Williams analyzed Medicare records from 1999 to 2014, focusing on U.S. residents between the ages of 65 and 99. Ultimately the research team studied 6.3 million Medicare beneficiaries. About 2 million of those moved from one U.S. "commuting zone" to another, and the rest were a random 10 percent sample of people who had not moved over the 15-year study period. (The U.S. Census Bureau defines about 700 commuting zones nationally.)

A central element of the study involves seeing how different people who were originally from the same locations fared when moving to different destinations. In effect, says Finkelstein, "The idea is to take two elderly people from a given origin, say, Boston. One moves to low-mortality Minneapolis, one moves to high-mortality Houston. We then compare how long each lives after they move."

Different people have different health profiles before they move, of course. But Medicare records include detailed claims data, so the researchers applied records of 27 different illnesses and conditions -- ranging from lung cancer and diabetes to depression -- to a standard mortality risk model, to categorize the overall health of seniors when they move. Using these "very, very rich pre-move measures of their health," Finkelstein notes, the researchers tried to account for pre-existing health levels of seniors from the same location who moved to different places.

Still, even assessing people by 27 measures does not completely describe their health, so Finkelstein, Gentzkow, and Williams also estimated what fraction of people's health conditions they had not observed -- essentially by calibrating the observed health of seniors against health capital levels in places they were moving from. They then consider how observed health varies across individuals from the same location moving to different destinations and, assuming that differences in unobserved health -- such as physical mobility -- vary in the same way as observed differences in health, they adjust their estimates accordingly.

All told, the study found that many urban areas on the East and West Coasts -- including New York City, San Francisco, and Miami -- have positive effects on longevity for seniors moving there. Some Midwestern metro areas, including Chicago, also score well.

By contrast, a large swath of the deep South has negative effects on longevity for seniors moving there, including much of Alabama, Arkansas, Louisiana, and northern Florida. Much of the Southwest, including parts of Texas, Oklahoma, New Mexico, and Arizona, fares similarly poorly.

The scholars also estimate that health capital accounts for about 70 percent of the difference in longevity across areas of the U.S., and that location effects account for about 15 percent of the variation.

"Yes, health capital is important, but yes, place effects also matter," Finkelstein says.

The Charlotte Effect: What makes a difference?

Indeed, the significance of place effects on life expectancy is also evident in another pattern the study found. Some locations -- such as Charlotte, North Carolina -- have a positive effect on longevity but still have low overall life expectancy, while other places -- such as Santa Fe New Mexico -- have high overall life expectancy, but a below-average effect on the longevity of seniors who move there.

Again, the life expectancy of an area's population is not the same thing as that location's effect on longevity. In places where, say, smoking is highly prevalent, population-wide longevity might be subpar, but other factors might make it a place where people of average health will live longer. The question is why.

"Our [hard] evidence is about the role of place," Finkelstein says, while noting that the next logical step in this vein of research is to look for the specific factors at work. "We know something about Charlotte, North Carolina, makes a difference, but we don't yet know what."

With that in mind, Finkelstein, Gentzkow, and Williams, along with other colleagues, are working on a pair of new studies about health care practices to see what impact place-based differences may have; one study focuses on doctors, and the other looks at the prescription opioid epidemic.

In the background of this research is a high-profile academic and policy discussion about the impact of health care utilization. One perspective, associated with the Dartmouth Atlas of Health Care project, suggests that the large regional differences in health care use it has documented have little impact on mortality. But the current study, by quantifying the variable impact of place, suggest there may be, in turn, a bigger differential impact in health care utilization yet to be identified.

For her part, Finkelstein says she would welcome further studies digging into health care use or any other factor that might explain why different places have different effects on life expectancy; the key is uncovering more hard evidence, wherever it leads.

"Differences in health care across places are large and potentially important," Finkelstein says. "But there are also differences in pollution, weather, [and] other aspects. … What we need to do now is get inside the black box of 'the place' and figure out what it is about them that matters for longevity."

The study was supported, in part, by the National Institute on Aging, the National Science Foundation, and the Stanford Institute for Economic Policy Research.


Story Source:

Materials provided by Massachusetts Institute of Technology. Original written by Peter Dizikes. Note: Content may be edited for style and length.


Journal Reference:

  1. Amy Finkelstein, Matthew Gentzkow, Heidi Williams. Place-Based Drivers of Mortality: Evidence from MigrationAmerican Economic Review, 2021; 111 (8): 2697 DOI: 10.1257/aer.20190825

Immunotherapy for HPV+ head and neck cancer

 A new study from scientists at Emory Vaccine Center and Winship Cancer Institute of Emory University reports that the immune cells that are the major targets of immune checkpoint inhibitors are present in tumors from head and neck cancer patients.

The study focuses on head and neck tumors that are positive for human papillomavirus (HPV), which is becoming one of most common types of head and neck cancers treated in the Western world. The results are scheduled for publication in Nature.

It suggests checkpoint inhibitors, which have transformed the treatment of several types of cancer, could be uniquely effective against this type of head and neck cancer. The results also indicate that the experimental approach of therapeutic vaccination for HPV+ cancer could be broadened to include more elements of the virus, to potentially trigger a broader and stronger immune response.

Researchers from Rafi Ahmed's lab at Emory Vaccine Center collaborated with the co-directors of the Winship Head and Neck Cancers working group, oncologists Nabil Saba, MD and Mihir Patel, MD, to obtain samples from patients with head and neck tumors early in the course of treatment.

"About five years ago, we began to have an influx of patients that sought out our center for surgical treatment," Patel says. "We often heard some variation of a similar story: I was sick with cold-like symptoms and once that resolved this I noticed swelling in a lymph node on the side of my neck. Stories like this made us think about how the immune system might play a unique role, different than typical smoking-related head and neck cancers."

The team wanted to learn more about the different kinds of CD8 or "killer" T cells present within the cancers; CD8 T cells are specialized immune cells capable of detecting and killing virus-infected or tumor cells, if they are not constrained by regulatory signals. The inhibitory receptor PD-1 is highly expressed on exhausted CD8 T cells in chronic viral infections and cancer, and stem-like PD-1CD8 T cells are crucial for maintaining tumor-specific CD8 T cell responses. The majority of currently available checkpoint inhibitors, such as pembrolizumab and nivolumab, block the PD-1 signaling pathway.

"Our results show that a subset of HPV-specific CD8 T cells in the tumor exhibits a striking resemblance to the stem-like CD8 T cells our lab has previously defined in mouse models as proliferating in response to PD-1 blockade," says Andreas Wieland, PhD, co-lead author of the paper and an instructor in Ahmed's lab.

"It is reasonable to assume that these cells would similarly provide a proliferative burst in response to PD-1 blockade in these patients. However, this remains to be formally tested."

HPV-positive tumors do have a relatively good response to conventional forms of treatment such as radiation and chemotherapy, Wieland adds. The group of patients studied at Winship was treatment-naïve when tumor samples were obtained; how radiation and chemotherapy affect the number and phenotype of T cells in the tumor needs additional investigation.

"These findings greatly enhance our understanding of CD8 T cell responses in the tumor micro-environment in HPV-related oropharynx cancers, and likely other virally mediated tumors," Saba says. "It confirms the existence of the different lineages necessary for an effective T cell specific anti-tumor response. Taking advantage of the local immune-response by avoiding its possible early elimination by traditional therapeutic modalities may pave the way to an improved clinical outcome for patients. It may have implications for how best to incorporate immunotherapy in the treatment of other virally mediated tumors."

"We now have an inclination that incorporating immune therapy with PD-1 blockade prior to surgery or radiation may benefit patients," Patel says. "We are actively in the process of developing 'window of opportunity' studies to understand this.

Looking at both primary tumors and metastatic lymph nodes, the researchers were able to detect both tumor-specific stem-like CD8 T cells, which can proliferate in response to HPV peptides, and more terminally differentiated cells that do not proliferate. In contrast to significant numbers of tumor-specific CD8 T cells in the tumors, tumor-specific cells appeared at a very low abundance in patients' blood, suggesting that they preferentially reside in tumors. The team also found that the different CD8 T cell subsets in the tumor microenvironment differ in their localization, with stem-like cells residing in distinct niches within the stroma and away from the tumor cells themselves.

Concentrating on HPV-positive tumors in this study facilitated the study of tumor-specific T cells with defined specificities across several patients as the virus is providing a defined set of tumor-associated antigens, whereas in other types of cancer the antigens caused by mutations will vary from individual to individual.

Co-first authors of the paper are Haydn Kissick, PhD, assistant professor of urology and microbiology and immunology, and Christiane Eberhardt, MD, a former postdoctoral fellow in Ahmed's lab who is now at the University of Geneva. Patel is also associate professor of otolaryngology at Emory University School of Medicine. Saba is professor and Vice Chair in the Department of Hematology and Medical Oncology.

The research was supported by a pilot grant from Winship Cancer Institute, the Ambrose Monell Foundation, the T.J. Martell Foundation, the National Institute of Allergy and Infectious Diseases (5U19AI057266, P01AI056299), the National Cancer Institute (R00CA197891), the Oliver S. and Jennie R. Donaldson Charitable Trust, the James M. Cox Foundation and James C. Kennedy, the Prostate Cancer Foundation, and a Triological Society Research Career Development Award.


Story Source:

Materials provided by Emory Health SciencesNote: Content may be edited for style and length.


Journal Reference:

  1. Christiane S. Eberhardt, Haydn T. Kissick, Mihir R. Patel, Maria A. Cardenas, Nataliya Prokhnevska, Rebecca C. Obeng, Tahseen H. Nasti, Christopher C. Griffith, Se Jin Im, Xu Wang, Dong M. Shin, Mary Carrington, Zhuo G. Chen, John Sidney, Alessandro Sette, Nabil F. Saba, Andreas Wieland, Rafi Ahmed. Functional HPV-specific PD-1 stem-like CD8 T cells in head and neck cancerNature, 2021; DOI: 10.1038/s41586-021-03862-z

Nasal cartilage relieves osteoarthritis in the knee

 Cartilage cells from the nasal septum can not only help repair cartilage injuries in the knee -- according to researchers from the University of Basel and the University Hospital of Basel, they can also withstand the chronic inflammatory tissue environment in osteoarthritis and even counteract the inflammation.

A research team at the Department of Biomedicine of the University of Basel and the University Hospital of Basel is cultivating cartilage tissue from cells of the nasal septum to repair articular cartilage in the knee. The team led by Professor Ivan Martin and Professor Andrea Barbero has already succeeded in doing this in initial clinical studies on isolated cartilage damage, and they have now reported that the approach could also be suitable for degenerative joint diseases such as osteoarthritis. Their findings have been published in the journal Science Translational Medicine.

Osteoarthritis is associated with cartilage degradation, which can cause severe pain and reduce mobility. The therapeutic approach up to now aims at palliative treatment of the inflammation and pain until a knee joint replacement by a prosthetic implant becomes unavoidable. Joint prostheses, however, have a limited durability, which makes the treatment problematic, especially in younger patients.

From the nose to the knee

A possible alternative could be to repair the articular cartilage using engineered cartilage tissue. To this end, the research team, in collaboration with orthopedic and plastic surgeons from the University Hospital of Basel, takes a tissue sample from a patient's nasal septum, cultivates the isolated cartilage cells and uses them to grow a cartilage layer that is then surgically implanted into the knee joint.

Unlike traumatic and confined cartilage defects, for example following sports injuries, the tissue environment in the osteoarthritic knee is characterized by persistent inflammatory reactions. "First we had to test whether the cartilage replacement was attacked and degenerated by the inflammatory factors," explains Ivan Martin.

The researchers led by Professor Martin's doctoral student Lina Acevedo Rua, project leader Dr. Karoliina Pelttari and orthopedic surgeon Dr. Marcus Mumme initially tested the cultured human cartilage tissue in the presence of inflammatory factors in various models in the laboratory and in small experimental animals. They then tested the durability of the cartilage tissue under simultaneous inflammatory and mechanical stress, using cartilage cells from the nose of sheep in the osteoarthritic knee joint of the same animals.

Cartilage cells with anti-inflammatory properties

The results of the animal experiments were encouraging -- not only did the tissue engineered from nasal cartilage cells prove to be extremely robust, it also seemed to counteract the inflammatory reactions. Further analysis revealed that this effect could be due to the fact that a molecular signaling pathway that is chronically upregulated in osteoarthritis (the WNT signaling pathway) was repressed by the presence of the nasal cartilage cells.

Explaining the amazing properties of the nasal cartilage, Professor Martin says: "Unlike the cartilage tissue in the joints, these cartilage cells originate from precursor cells of the neuroectoderm and therefore have a distinct regenerative and adaptive capacity (plasticity). Tissue grown from nasal cartilage cells seems also to retain these special properties."

Following the successful trials on animals, the researchers also tested the approach on two young patients suffering from severe osteoarthritis, likely due to misalignment of the leg bones. Their alternative treatment would have been a knee joint prosthesis.

Less pain, recovered joint

Following the implantation of the cartilage engineered from the patients' own nasal cartilage cells, the two subjects reported a reduction in pain and increased quality of life. In one of the two patients, the researchers were also able to determine via MRI images that the bones in the knee joint were further apart than previously -- an indication of the joint's recovery. With the second patient, they were unable to perform any MRI scans due to travel restrictions during the pandemic, and could only interview him to derive a subjective assessment.

In addition, as the misalignment of the bones in both patients could be surgically corrected and thus the most likely cause of their osteoarthritis eliminated, the researchers are confident that patients will be able to manage without knee joint prostheses, at least for some time.

"Our results have enabled us to lay the biological foundation for a therapy, and we are cautiously optimistic" says Martin. This approach will first have to be further assessed for the treatment of patellofemoral osteoarthritis through in-depth clinical trials, for which the team is receiving financial support as part of an Innovation Focus ("Regenerative Surgery") by the University Hospital of Basel. The researchers also aim to further develop the method for other types of osteoarthritis in order to be able to treat a broader spectrum of patients.


Story Source:

Materials provided by University of BaselNote: Content may be edited for style and length.


Journal Reference:

  1. Lina Acevedo Rua, Marcus Mumme, Cristina Manferdini, Salim Darwiche, Ahmad Khalil, Morgane Hilpert, David A. Buchner, Gina Lisignoli, Paola Occhetta, Brigitte von Rechenberg, Martin Haug, Dirk J. Schaefer, Marcel Jakob, Arnold Caplan, Ivan Martin, Andrea Barbero, Karoliina Pelttari. Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defectsScience Translational Medicine, 2021; 13 (609) DOI: 10.1126/scitranslmed.aaz4499

Brazil's Bolsonaro signs law that could break COVID-19 vaccine patents

 Brazilian President Jair Bolsonaro on Thursday signed off on a law allowing for vaccine and medication patents to be broken in a public emergency, such as the COVID-19 pandemic.

But the right-wing leader vetoed the provisions that patent holders would need to transfer the knowledge and supply the raw materials needed to duplicate the vaccines and medications.

According to a statement from his office, those provisions were seen as being too difficult to implement and discouraging investment in researching new technologies.

Bolsonaro had previously criticized the law as potentially harming Brazil's commercial relationships.

Under the law, the president is the one who would determine when to break a patent in an emergency.

https://www.msn.com/en-us/news/world/brazils-bolsonaro-signs-law-that-could-break-covid-19-vaccine-patents/ar-AAO2rab