Saturday, April 15, 2023

Single-use surgical items contribute two-thirds of carbon footprint of products used in common operations

Peer-Reviewed Publication

SAGE

A new analysis of the carbon footprint of products used in the five most common surgical operations carried out in the NHS in England shows that 68% of carbon contributions come from single-use items, such as single-use gowns, patient drapes and instrument table drapes. Published by the Journal of the Royal Society of Medicine, the analysis highlights significant carbon contributors were the production of single use items and their waste disposal, together with processes for decontaminating reusable products.

Researchers from Brighton and Sussex Medical School and the University of Warwick carried out the study, which is the first to systematically evaluate the carbon footprint of products used in common operations. The analysis was based on direct observation of operating rooms across three sites of University Hospitals Sussex NHS Foundation Trust.

Applying the carbon dioxide equivalent (CO2e), the standard unit for measuring carbon footprints, to each of the operations, the researchers showed that the operation with the highest product carbon footprint was knee replacement (85.5kg CO2e). This was followed by gall bladder removal (20.3kg CO2e), carpal tunnel decompression surgery (12.0kg CO2e), hernia repair (11.7kg CO2e) and tonsillectomy (7.5kg CO2e).

Across the five operations, the researchers found that relatively few products (23%) were responsible for more than 80% of the product carbon footprint. This indicates that strategies for reducing greenhouse gas emissions associated with surgical operations should focus on the few products with highest emissions, typically large single-use (often plastic) items.

Lead researcher Dr Chantelle Rizan, Clinical Lecturer in Sustainable Healthcare at Brighton and Sussex Medical School, said: “Mitigating the carbon footprint of products used in resource-intensive areas such as surgical operating rooms will be important in achieving net zero carbon healthcare. Strategies should include eliminating or finding low carbon alternatives for products with the biggest contribution.”

Strategies to eliminate products, write the researchers, include avoiding non-sterile gloves, where they could be replaced with hand-washing, not opening gauze swab packs unless required and asking suppliers to remove rarely used items from single-use pre-prepared packs. The researchers also suggest that a number of single-use high carbon products have reusable alternatives. For example, single-use gowns, patient drapes and instrument table drapes were high carbon contributors in the study, yet the researchers note there is no evidence that reusable surgical textiles, which hold significant reductions in carbon footprint, are clinically inferior.

Dr Rizan concludes: “Eliminating single-use items or switching to reusables where feasible, alongside optimising associated decontamination processes and waste segregation and recycling, could reduce product carbon footprint by one third. This model was based on reusable alternatives already on the market, and this figure may be surpassed where industry rises to the challenge of sustainable surgical product innovation.”

Disclaimer: AAAS 

BIG PHARMA PRICE GOUGING

Study: Anti-obesity medications could be sold for lower prices

Change in cost may improve affordability, access to treatment

Peer-Reviewed Publication

THE OBESITY SOCIETY

ROCKVILLE, Md.—New research shows that several anti-obesity medications could be manufactured and profitability sold worldwide at far lower estimated lower prices compared to their high costs, according to a new study in Obesity, The Obesity Society’s (TOS) flagship journal.

Access to medicine is a fundamental element of the human right to health. While the obesity pandemic grows, especially amongst low-income communities, effective medical treatments remain inaccessible for millions in need. Our study highlights the inequality in pricing that exists for effective anti-obesity medications, which are largely unaffordable in most countries. However, we show that these drugs can actually be produced and sold profitably for low prices. A public health approach that prioritizes improving access to medications should be adopted, instead of allowing companies to maximize profits,” said Jacob Levi, Intensive Care Medicine, Royal Free Hospital NHS Trust, London, United Kingdom. Levi is the corresponding author of the study.

Experts explain that the increasing recognition that diet and exercise alone is unlikely to result in sustained weight loss had led to renewed interest in medication to supplement lifestyle changes. Randomized controlled trials have demonstrated positive results with oral and injectable medications. However, these medications remain prohibitively expensive in most countries. Such high prices make it challenging for millions of people to afford the medications and obtain access to treatment.

“It would be great if everyone had affordable access to all medicines that might improve their health. Yet that is simply not possible, nor will it ever be. What is truly needed is a better way to ration the health care dollars currently available in efforts to maximize population health. That is the challenge ahead not just for anti-obesity medications but for all treatments,” said Eric A. Finkelstein, professor, Duke-NUS Medical School, Singapore, in a commentary about the study.

On the other hand, the authors have called for a public health based approach to obesity management similar to that used with other diseases. Andrew Hill, Department of Pharmacology and Therapeutics, University of Liverpool, United Kingdom, supervising author of the study, commented, "Worldwide, more people are dying from diabetes and clinical obesity than HIV, tuberculosis and malaria combined now. Millions of lives have been saved by treating infectious diseases at low cost in poor countries. Now we need to repeat this medical success story, with mass treatment of diabetes and clinical obesity at low prices. Pharmaceutical companies have an ethical responsibility to make their new treatments for diabetes and obesity available for anyone in need, in any country."

The study’s authors searched national drug price databases and collected information on six medications: orlistat, naltrexone/bupropion, topiramate/phentermine, liraglutide, semaglutide and tirzepatide across a range of 16 low-, middle- and high-income countries. In each country, researchers assessed multiple online national price databases and selected the lowest available price from each of the sources. Medications selected were chosen because they are proven effective and because they illustrate a range of different monotherapies, combination tablets and injectable treatments.

Estimated minimum prices (EMPs) for anti-obesity medications were calculated using established methodology using active pharmaceutical ingredients from the Panjiva database. EMPs were calculated per 30-day course and include costs of active pharmaceutical ingredients, excipients, formulation, taxation and 10% profit margin.

Results revealed that national prices of oral and injectable anti-obesity medications were significantly higher than calculated EMPs.

Oral Medications:

  • Orlistat: Prices for a 30-day course of treatment were greater than $100 in the United States and less than $1 in Vietnam. The calculated EMP from export API data was approximately $7 per 30-day course.
  • Naltrexone/bupropion: Costs for naltrexone/bupropion combination tablets range from $326 in the United States to $56 in South Africa compared with an EMP of $55 per 30-day course.
  • Topiramate/phentermine: Price data was only available in the United States since the medication is not licensed for use for weight loss in several countries because of safety concerns. Prices in the United States ranged from $120 to $199 per course compared with the EMP of the combination tablets at $5. Prices were also searched separately of topiramate and phentermine and combined with available data together from the United States, South Africa and Kenya. EMP’s for each drug individually were $0.86 for topiramate and $0.53 for phentermine (total of $1.39 per course) based on API export data.

Injectable Medications:

  • Liraglutide: Injectable anti-diabetic and weight loss agent liraglutide costs $1,418 in the United States and $252 in Norway. The EMP per 30-day course was $50. Researchers note that this price was calculated assuming the most efficient concentration and dosage of available pens for injection.
  • Semaglutide: National price data for subcutaneous semaglutide were all higher than EMPs ranging from $804 in the United States to $95 in Turkey. The EMP of subcutaneous semaglutide was calculated to be approximately $40 per 30-day course.
  • Tirzepatide: National price data was only available in the United States, where the medication was recently licensed for use in type 2 diabetes by the Food and Drug Administration. The medication is not licensed for obesity alone. Prices for 30-day course ranged from about $715.56 to $1,100.70. Insufficient data existed in the database to calculate an EMP.

The study’s authors note that EMPs are meant as realistic targets for competitive generic production rather than patented versions.

Caroline M. Apovian, MD, FTOS, co-director, Center for Weight Management and Wellness and professor of medicine at Harvard Medical School in Boston, Mass., commented, “Once we have shown that anti-obesity agents notably GLP-1 and combinations thereof lower cardiovascular risk, we can then demand universal insurance coverage of these agents. These agents used for obesity prior to the advent of type 2 diabetes, cardiovascular disease and other complications, have the power to reduce the cardiovascular burden and lower mortality worldwide.” Apovian was not associated with the research.

Other authors of the study include Junzheng Wang, Medical Sciences Office, Oxford University, Clinical Academic Graduate School, University of Oxford, Oxford, United Kingdom and Francois Venter, Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Venter has received support from the Bill and Melinda Gates Foundation, U.S. Agency for International Development, Uni-taid, SA Medical Research Council, Foundation for Innovative New Diagnostics, the Children’s Investment Fund Foundation, Gilead, ViiV, Mylan, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson & Johnson, Sanofi, Virology Education, SA HIV Clinicians Society and Dira Sengwe. The other authors declared no conflict of interest.

Funding for this study was provided by the Make Medicines Affordable/International Treatment Preparedness Coalition,  grant number  ITPC-MV_2020,https://makemedicinesaffordable.org/about/, and National Heart, Lung, and Blood Institute of the National Institutes of Health under award number UG3HL156388.

The study, titled “Estimated Minimum Prices and Lowest Available National Prices for Anti-obesity Medications: Improving Affordability and Access to Treatment,” is online and will be published in the print issue of Obesity in May 2023.

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The Obesity Society (TOS) is the leading organization of scientists and health professionals devoted to understanding and reversing the epidemic of obesity and its adverse health, economic and societal effects. Combining the perspective of researchers, clinicians, policymakers and patients, TOS promotes innovative research, education and evidence-based clinical care to improve the health and well-being of all people with obesity. For more information, visit www.obesity.org.

RACIST MEDICINE U$A

Black cancer patients 71% more likely to experience heart damage following chemotherapy treatment


Review examines racial disparities in cardiovascular adverse effects from chemotherapy

Reports and Proceedings

AMERICAN COLLEGE OF CARDIOLOGY

Chemotherapy is associated with an increased risk of treatment-related heart damage, including heart failure and cerebrovascular disease, for many patients. But a new meta-analysis, presented at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient 2023 conference, finds that Black patients or patients of African ancestry have 71% higher odds of cardiotoxicity following cancer treatment compared to White patients.

Cardiotoxicity is any heart damage stemming from cancer treatment or drugs, including chemotherapy agents and radiation. It can lead to several heart problems, including heart failure, cardiomyopathy and irregular heart rhythms. Certain cancer treatments have a higher risk of causing cardiotoxicity, including anthracyclines, which are used to treat leukemias, lymphomas, and cancers of the breast, stomach, uterus, ovary and lung.

“Unfortunately, we were not surprised [by the findings]. Research shows that Black patients have poorer outcomes for almost every disease,” said Wondewossen Gebeyehu, BSc, a medical student at the University of Toronto and lead author of the study. “In this case, one could have expected that the differences would be minimal since it is the chemotherapy that is injuring the heart, and we would expect the same chemotherapy to be given to Black and non-Black patients with a given cancer. However, this systematic review indicates that the inequities in health outcomes extends to the odds of cardiotoxicity after cancer treatment.”

Researchers performed a systematic search of several databases—including Medline, Embase, Pubmed and others—of all studies reporting on cardiovascular toxicity in cancer patients of different racial/ethnic background receiving chemotherapy. After screening 7,057 studies, 24 studies representing 683,749 participants were included in the final review. Black race or African ancestry was associated with 71% increased odds of chemotherapy-associated cardiotoxicity; it was also associated with increased odds of a congestive heart failure diagnosis.

“These results may reflect the direct effects of racism, particularly structural racism, which leads to worse determinants of health for Black patients. It is well-documented that most health care settings are not perceived as safe by Black patients, which may increase their vulnerability to disease and decrease opportunities for preventative care,” Gebeyehu said. “Furthermore, decreased representation of Black patients in clinical trials may lead to treatments being developed that are not as effective or which may be riskier for Black patients. Importantly, these results should prompt further inquiry into the many possible contributors to disparities observed in Black patients.”

According to the researchers, the study quantifies the increased odds of chemotherapy-associated cardiotoxicity for Black cancer patients. The study also highlights the need for further study to determine underlying factors contributing to these disparities so they can be reduced.

“The most important message for patients is that they should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Gebeyehu said. “For clinicians, it is important to be aware of these higher odds of cardiotoxicity faced by Black patients. Understanding these disparities will hopefully lead to clinicians having more conversations around reducing cardiovascular risk associated with chemotherapy and targeted efforts to cater to groups at higher risk.”

The American College of Cardiology (ACC) is the global leader in transforming cardiovascular care and improving heart health for all. As the preeminent source of professional medical education for the entire cardiovascular care team since 1949, ACC credentials cardiovascular professionals in over 140 countries who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. Through its world-renowned family of JACC Journals, NCDR registries, ACC Accreditation Services, global network of Member Sections, CardioSmart patient resources and more, the College is committed to ensuring a world where science, knowledge and innovation optimize patient care and outcomes. Learn more at www.ACC.org or follow @ACCinTouch.

 

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Racial, ethnic differences in barriers faced by medical college admission test examinees

JAMA Health Forum

Peer-Reviewed Publication

JAMA NETWORK

About The Study: In this study of 81,755 Medical College Admission Test examinees, American Indian or Alaska Native, Black, and Hispanic students reported lower parental educational levels, greater educational and financial barriers, and greater discouragement from pre-health advisers than white students. These barriers may deter groups underrepresented in medicine from applying to and matriculating at medical school. 

Authors: Jessica Faiz, M.D., M.S.H.P.M., of the Veterans Affairs Greater Los Angeles Healthcare System and UCLA in Los Angeles, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamahealthforum.2023.0498)

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Black representation in the primary care physician workforce and its association with population life expectancy


Peer-Reviewed Publication

JAMA NETWORK

About The Study: The findings of this study of survival outcomes for 1,618 U.S. counties suggest that greater representation of Black primary care physicians (PCPs) in the PCP workforce is associated with improved survival-related outcomes for Black individuals, although there was a dearth of U.S. counties with at least one Black PCP during each study time point. Investments to build a more representative PCP workforce nationally may be important for improving population health. 

Authors: John E. Snyder, M.D., M.S., M.P.H., and Rachel D. Upton, Ph.D., of the U.S. Department of Health and Human Services in Rockville, Maryland, are the corresponding authors. 

(doi:10.1001/jamanetworkopen.2023.6687)

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About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

Sowing seeds of change: SELINA's first thematic workshop

A three-day workshop in Sofia brought together experts and stakeholders to discuss seeds of transformative change in the context of biodiversity and ecosystem services

Meeting Announcement

PENSOFT PUBLISHERS

Highlights from the SELINA first thematic workshop in Sofia, Bulgaria 

IMAGE: HIGHLIGHTS FROM THE SELINA FIRST THEMATIC WORKSHOP IN SOFIA, BULGARIA view more 

CREDIT: PENSOFT PUBLISHERS

From 27 to 31 March 2023, nearly 120 experts and key stakeholders from public and private sectors gathered together for a workshop in Sofia, Bulgaria, to deliberate the enabling factors and barriers to implementing biodiversity and ecosystem services into decision making processes. The attendees of the meeting were representing various business, government, civil society, and science sectors and were coming from all 27 EU member states, Israel, Norway, Switzerland and North Macedonia.

The workshop was organised within the framework of the SELINA collaborative project, which is funded under the EU Horizon programme and contributes to reshaping decision-making processes within the public and private sectors by improving the uptake of biodiversity, ecosystem conditions, and ecosystem services information. It was the first one in a series of interactive workshops planned within the project to support the constant flow of information, joint creation and mutual exchange of knowledge.

What are the barriers and enabling factors when it comes to implementing biodiversity and ecosystem services indicators in decision making?

SELINA workshop participants pointed as the most common barriers resistance to change and scepticism, as well as lack of capacity, collaboration, regulations, knowledge, accurate data, common language, and political will.

Workshop attendees also identified a number of enabling factors that could in turn help to implement biodiversity and ecosystem services and related indicators in decision-making processes.They mentioned communication, stakeholder engagement, data availability, EU regulations, synergies and collaboration as possible drivers for successful implementation. Participants recognised SELINA as an initiative that can help to facilitate the mainstreaming of biodiversity and ecosystem services in Europe especially through providing guidance and promoting good examples and practices.

The SELINA project will in fact provide guidance through its key output – the Compendium of Guidance (CoG) that is planned to serve public and private decision makers. The CoG will be developed through a co-creation process with experts and stakeholders that started already in Sofia, where workshop participants provided the first round of input into the structure and the potential content of the document. They were consulted about the needs, interests and desires they have for the CoG and also deliberated how the CoG could translate the technical advancements of the project into user-friendly guidance products to support decision-making needs and in what forms.

Exploring local ecosystems and an urban heat island effect demonstration

To get hands-on experience with one of the altogether 15 SELINA's demonstration projects and to have the chance to explore local ecosystems, participants took a field trip around Sofia. They got engaged in an urban field demonstration by Macroplan, Bulgaria, who performed a drone-based mapping exercise of the spatial distribution of land surface temperatures and made an assessment of the urban heat island effect. The urban heat island was presented as one of the most significant examples of the impact of cities on the environment and human health.

Participants then visited the Botanical Garden of the Bulgarian Academy of Sciences that maintains the richest collection of plants in Bulgaria including over 4 500 types and forms of plants, which represent over 1% of the variety of higher plants in the world. The public function of the Garden is related to the issues of exploration and conservation of biodiversity and the dissemination of knowledge about it among the broadest public strata, with a view to building a relationship to the sustainable management of biodiversity. The field trip finished with a visit to a local nature site where participants had the opportunity to explore local ecosystems and got to know the biodiversity of Vitosha, one of the first nature parks in Bulgaria and on the Balkan Peninsula.

“The first SELINA workshop is an important milestone for the project. Within these three days, we have successfully sowed the seeds of change. Now we want to make them grow through continued collaboration and collective action towards ensuring evidence-based decision-making that supports the protection, restoration, and sustainable use of our environment,” shared the coordinator of SELINA, Prof. Dr. Benjamin Burkhard from Leibniz University Hannover, Germany.

For more insights from the workshop and other SELINA activities, check out the SELINA website and follow SELINA on social media.

The next SELINA workshop will be held in Madrid in October 2023.

A rechargeable battery made from food

It is the first ever-made rechargeable edible battery; described on Advanced materials it may be applied in health diagnostics, food quality monitoring and edible soft robotics. It has been realized at Istituto Italiano di Tecnologia.


Peer-Reviewed Publication

ISTITUTO ITALIANO DI TECNOLOGIA - IIT

A rechargeable battery made from food 

IMAGE: A TEAM OF RESEARCHERS AT THE ISTITUTO ITALIANO DI TECNOLOGIA (IIT-ITALIAN INSTITUTE OF TECHNOLOGY) HAS CREATED A TOTALLY EDIBLE AND RECHARGEABLE BATTERY, STARTING FROM MATERIALS THAT ARE NORMALLY CONSUMED AS PART OF OUR DAILY DIET. THE PROOF-OF-CONCEPT BATTERY CELL HAS BEEN DESCRIBED IN A PAPER PUBLISHED IN THE ADVANCED MATERIALS JOURNAL. THE POSSIBLE APPLICATIONS ARE IN HEALTH DIAGNOSTICS, FOOD QUALITY MONITORING AND EDIBLE SOFT ROBOTICS. view more 

CREDIT: IIT-ISTITUTO ITALIANO DI TECNOLOGIA

Milan (Italy), 13th April 2023 – A team of researchers at the Istituto Italiano di Tecnologia (IIT-Italian Institute of Technology) has created a totally edible and rechargeable battery, starting from materials that are normally consumed as part of our daily diet. The proof-of-concept battery cell has been described in a paper, recently published in the Advanced Materials journal. The possible applications are in health diagnostics, food quality monitoring and edible soft robotics.

The study has been realized by the group of Mario Caironi, coordinator of the Printed and Molecular Electronics laboratory of the IIT Center in Milan (Italy); Caironi has been focusing on the study of the electronical properties of food and its by-products, in order to unite them with edible materials and create new edible electronic materials. In 2019, Caironi won a 2-million-euro ERC consolidator grant for the ELFO Project, which explores the edible electronics field.

Edible electronics is a recently growing field that could have a great impact on the diagnosis and treatment of gastrointestinal tract diseases, as well as on the food quality monitoring. One of the most interesting challenges in the development of future edible electronic systems is to realize edible power sources.

The IIT’s research group took inspiration from the biochemical redox reactions that happens in all the living beings, and developed a battery that utilizes riboflavin (vitamin B2, found for example in almonds) as anode and quercetin (a food supplement and ingredient, present in capers, among others) as cathode. Activated charcoal (a widespread over-the-counter medication) was used to increase electrical conductivity, while the electrolyte was water-based. The separator, needed in every battery to avoid short circuits, was made from nori seaweed, the kind found in sushi. Then, electrodes were encapsulated in beeswax from which two food-grade gold contacts (the foil used by pastry chefs) on a cellulose derived support come out.

The battery cell operates at 0.65 V, a voltage low enough not to create problems in the human body when ingested. It can provide current of 48 μA for 12 minutes, or a few microamps for more than an hour, enough to supply power to small electronic devices, such as low-power LEDs, for a limited time.

This example of fully edible rechargeable battery, the first one ever made, would open the doors to new edible electronic applications.

“Future potential uses range from edible circuits and sensors that can monitor health conditions to the powering of sensors for monitoring food storage conditions. Moreover, given the level of safety of these batteries, they could be used in children toys, where there is a high risk of ingestion. Actually, we are already developing devices with greater capacity and reducing the overall size. These developments will be tested in future also for powering edible soft robots”, pointed out the research coordinator Mario Caironi.

This edible battery is also very interesting for energy storage community. Building safer batteries, without usage of toxic materials, is a challenge we face as battery demand soars. While our edible batteries won’t power electric cars, they are a proof that batteries can be made from safer materials than current Li-ion batteries. We believe they will inspire other scientists to build safer batteries for truly sustainable future”, added Ivan Ilic, coauthor of the study.

Researchers decode the secret of bears in pursuit of new treatment against blood clots


Researchers at Aarhus University have used unconventional methods and spent 13 years mapping the hibernating bear's defence against blood clots. This could be the first step towards a new type of medication without side effects.

Peer-Reviewed Publication

AARHUS UNIVERSITY

Bear analysis 

IMAGE: RESEARCHERS FROM AARHUS UNIVERSITY, TOGETHER WITH GERMAN COLLEAGUES, HAVE SPENT 13 YEARS FIGURING OUT WHY BEARS DON'T GET BLOOD CLOTS AND LOSE MUSCLE MASS DURING HIBERNATION. THE RESULT COULD LEAD TO NEW GROUNDBREAKING DRUGS. view more 

CREDIT: OLE FRØBERT, AARHUS UNIVERSITY

For most people, prolonged inactivity is associated with an increased risk of developing blood clots due to limited blood flow in the veins. But why doesn't the same apply to bears that, with a resting heart rate of ten beats per minute, sleep through the winter months without moving at all?

This wonder more than 13 years ago led a team of researchers from Aarhus University, Aarhus University Hospital, and a group of German researchers to embark on an unusual research project - the goal was to decode the bear's secret.

Now, they have finally succeeded, and it turns out that the answer lies in a particular protein that normally helps fight inflammatory conditions in the body and ensures that blood clots when bleeding occurs.

"This protein is the key to a natural mechanism to protect the body against blood clots when it cannot move. This finding is very exciting as it has the potential to be of great importance for people at risk of developing blood clots due to inactivity," explains Professor Ole Frøbert of the Department of Clinical Medicine at Aarhus University.

Clotting blood platelets

Together with the team of researchers, he has previously demonstrated that the bear's blood platelets, which are essential for the development of blood clots, are less likely to stick together in the winter. To find the explanation for the less sticky blood platelets, the researchers took blood samples from wild bears in Sweden and compared the results between summer and winter.

"By meticulous examination of proteins from blood platelets, we discovered that the protein HSP47 was almost absent in the winter. And when we examined mice in which the gene that produces HSP47 was removed, we saw that the mice were hardly able to form blood clots," explains Ole Frøbert.

All bears have been sedated in connection with the studies, which are approved by the animal ethics authorities.

Treatment without side effects?

The question is whether it is possible to transfer the bear's natural mechanism to human physiology and, for example, activate it in patients who are forced to prolonged inactivity - e.g. people who are paralyzed due to spinal cord injuries.

There are already several drugs that are widely used to prevent blood clots. The common feature of all of them is that they are associated with the risk of bleeding, which can be life-threatening.

Therefore, Ole Frøbert sees great prospects for the development of new drugs against blood clots based on the findings of the study.

"There are many mechanisms that regulate blood coagulation, and we have demonstrated yet another. Since we have succeeded in downregulating HSP47 with gene manipulation in mice, we believe that the new mechanism may open up the development of a new type of gentle, preventive treatment with significantly lower risk of bleeding and other side effects," he says.

Further research in the field will include, among other things, studies of whether certain patients spontaneously activate downregulation of the HSP47 protein, as these will not require blood-thinning medication, for example, after a stroke.

"We are also continuing our research on the bear model, as it may potentially prove to be a Swiss Army knife with solutions to a wide range of major challenges. Currently, we are working to understand why bears - unlike inactive humans - do not lose muscle mass during hibernation," explains Ole Frøbert.

You can read more about the study, which has just been published in the journal Sciencehere:

About the study

  • Study type: Basic research. Translational research.
  • Collaborators: Department of Cardiology, LMU Munich; Max Planck Institute Munich; Örebro University Hospital; Scandinavian Brown Bear Research Project; Norwegian Institute for Nature Research. Funding: German Research Foundation; German Excellence Initiative; European Research Council; NASA; Norwegian Environment Agency; and the Swedish Environmental Protection Agency.
  • Conflicts of interest: None.
  • Link to publication: https://www.science.org/doi/10.1126/science.abo5044

Benefits of “zombie” cells: Senescent cells aid regeneration in salamanders

Scientists show that so called senescent cells, i.e., cells that have permanently stopped dividing, boost production of new muscle cells to enhance regeneration of lost limbs in salamanders.

Peer-Reviewed Publication

TECHNISCHE UNIVERSITÄT DRESDEN

Salamander 

IMAGE: THE SALAMANDER SPECIES STUDIED BY THE YUN GROUP: A RED SPOTTED NEWT NOTOPHTHALMUS VIRIDESCENS. view more 

CREDIT: MAXIMINA YUN

Senescent cells are cells that have permanently stopped dividing in response to cellular stress but have not died. As organisms age, the number of senescent cells in the body increases. This accumulation is currently considered one of the hallmarks of aging and has been linked to a variety of diseases, including cancer. However, the true nature of these cells may be more complex and context-dependent.

A growing body of evidence suggests that senescent cells may also have beneficial effects, such as wound healing or preventing tissue scarring. “A few years ago, our group found that senescent cells were present at key stages of salamander limb regeneration. Interestingly, other groups subsequently found these cells in other regeneration contexts, including in mammals. We therefore wanted to find out whether these cells contribute in any way to regeneration itself,” explains Dr. Maximina Yun, research group leader at the Center for Regenerative Therapies Dresden (CRTD) and the Cluster of Excellence Physics of Life (PoL) at TU Dresden and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG).

Senescent Cells Promote Regeneration

The researchers in the Yun’s group study salamanders. These animals have unique regeneration abilities and are able to re-grow many organs of their bodies, including lost limbs. “Salamander limb regeneration is a fascinating process. In a matter of weeks, they re-grow a fully functional limb,” explains Dr. Yun.

To check if the presence of senescent cells influences the limb regeneration process, researchers in the Yun group found a way to modulate the number of senescent cells in the wound. The team observed that the presence of senescent cells enhanced the regeneration process.

“When more senescent cells were present in the wound, the animals developed a larger regeneration bud, or - as we call it – blastema. This is a collection of cells that are going to form all the needed tissues in the new limb. The larger the blastema, the more cells are there to regrow the limb and the quicker the regeneration process. The presence of senescent cells seemed to ‘fuel’ the regeneration process,” Dr. Yun says.

“Zombie” Signaling Promotes New Muscle Cells

Looking more closely at the blastema with and without the influence of the senescent cells, the Yun team uncovered a new mechanism that enhances the regeneration process and found that the presence of senescent cells increased the number of regenerating muscle cells. They showed that senescent cells secrete factors that stimulate nearby muscle tissue to take a developmental step back and produce new muscle.

“Our results show that senescent cells use cell-cell communication to influence the regeneration process. They secrete molecules that signal to mature muscle fibers to dedifferentiate into muscle progenitor cells. These cells can multiply themselves as well as differentiate into new muscle cells, thereby enhancing the regeneration process. This signaling appears to be an important part of promoting regeneration,” says Dr. Yun.

For now, the group focused on muscle, one of the most important tissues in the regenerating limb. However, the team is already investigating whether senescent cell signaling also contributes to the regeneration of other tissues.

Lessons From the Salamanders

Yun’s group is working with the salamanders to study regeneration and aging processes. “Salamanders are one of the few animal species that seem to defy the natural aging process. They do not develop typical signs of aging and do not accumulate age-related diseases such as cancer. They also have extraordinary healing abilities,” says Dr. Yun. The animals can regenerate almost any organ in their body.

Studying salamanders is helping Dr. Yun and her colleagues at the CRTD understand the principles of the regeneration process and, in the long run, may help solve the puzzle of why humans have very limited regenerative abilities.

Original Publication
Hannah E. Walters, Konstantin E. Troyanovskiy, Alwin M. Graf and Maximina H. Yun: Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation. Aging Cell (April 2023) Link: http://doi.org/10.1111/acel.13826

Resources:
Website of Dr. Yun’s group: https://tud.de/crtd/yun
Full resolution pictures: https://tud.link/2bx0