Noticias

• Nine experts will discuss healthy ageing, digital health solutions, sports performance, and rehabilitation on 5 February.

The Public University of Navarre (UPNA) and the biomedical research centre Navarrabiomed have organized the 9th International Conference on Physical Exercise, Health and Quality of Life, to be held on 5 February under the theme “From the Laboratory to Clinical, Sports and Community Practice.” Nine speakers will examine the role of physical exercise as a tool for promoting healthier ageing, the impact of digitalization on disease prevention and management, and the application of scientific evidence and technology in sports rehabilitation and performance.
The event, which is open to the public upon prior registration, will take place in the afternoon at the Faculty of Health Sciences of UPNA (Avenida de Barañáin, s/n, Pamplona).

The conference has been organized by the Physical Exercise, Metabolism and Functional Capacity Unit (EFIT) at Navarrabiomed, led by Mikel Izquierdo Redín, Professor in the Department of Health Sciences at UPNA. The event is supported by EGYM.

Topics to be discussed include the relationship between nutrition, metabolism and performance; exercise as a form of “medicine” after the age of 60; whether healthy ageing should be considered a disease; the evolution of digital solutions for managing type 2 diabetes; continuous patient monitoring through multiparametric platforms; the impact of technology and artificial intelligence in fitness and sports centres; scientific evidence surrounding so-called “Zone 2 training” (low-intensity exercise sustained over long periods); and technological applications in sports rehabilitation.

The event will open with welcoming remarks from Almudena Sánchez-Villegas, Dean of the Faculty of Health Sciences at UPNA, and Javier Gómez-Arrue Azpiazu, Director of Navarrabiomed. This will be followed by the keynote lecture, “Smart Nutrition: Synchronising Metabolism and Performance,” delivered by Javier González from the University of Bath (United Kingdom).

Three Thematic Sessions

The programme is structured into three thematic blocks. The first session, focused on healthy ageing, will feature presentations by Steve Harridge and Norman Lazarus, both researchers at King’s College London. The second session, dedicated to digital and technological solutions, will include contributions from Joaquín de Carlos Artajo (Reina Sofía Hospital and Tudela Health Area), Pablo Albizu Balerdi (CEO of 540), Rakel Herrero Colmenero (NAITEC), and Juan Ramón Gabino Marrero (Iberian Peninsula Director at EGYM). Following a break, the third session, centred on sports rehabilitation and performance, will bring together Pedro Valenzuela Tallón (University of Alcalá) and Juanjo Brau, former Head of Physiotherapy and Rehabilitation at FC Barcelona for 25 years. The conference will conclude with a question-and-answer session.

Featured Project: SENSORFIT-4HEART

Among the initiatives to be presented, particular attention will be given to SENSORFIT-4HEART, a strategic project led by Navarrabiomed and funded by the Government of Navarre through the 2023 Strategic R&D Projects Call of the Department of Industry and Business Ecological and Digital Transition, as well as by the European Regional Development Fund (ERDF) through the Navarre ERDF Programme 2021-2027.

The project aims to develop a new strategy for advancing the personalized treatment of patients with heart failure with preserved ejection fraction (HFpEF). It focuses on non-pharmacological approaches that empower patients in self-management and improve their quality of life.
Specifically, the research team is developing a tailored physical exercise programme for this patient population. The project involves a multidisciplinary consortium comprising professionals from ADItech, Cima Universidad de Navarra, NAITEC, and the companies Lorpeland and 540.

Individuals interested in attending the conference can register free of charge by contacting: efit@navarra.es.

• The BIOANCIENT project welcomes its first participant, Carmen, aged 100, and continues recruiting people born before 1928.

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BIOANCIENT, a project led by Navarrabiomed and funded by the Government of Navarra through the 2025-2028 Strategic R&D Project Grants, is now underway. The initiative aims to advance scientific knowledge on longevity and is recruiting individuals born before 1928 to help develop new preventive strategies and innovative diagnostic methods. Carmen, aged 100, is the first participant in the study, and her involvement marks the beginning of the research effort.

The study is continuing to recruit participants. Researchers are seeking individuals born before 1928 who reside in Navarra and wish to contribute to scientific advances in longevity and healthy ageing. Every participant provides valuable information that may help drive future diagnostic and therapeutic breakthroughs. Interested individuals or their relatives can contact the research team by email at bioancient@navarra.es or register through the online application form available for the study.

The BIOANCIENT project focuses on biological ageing, with the goal of understanding which genetic, epigenetic, and environmental factors influence both life expectancy and quality of life at advanced ages. In this context, BIOANCIENT seeks to identify targeted treatments that could lead to personalized preventive strategies capable of delaying ageing and preventing associated chronic diseases. It also aims to develop innovative diagnostic methods that enable the rapid and early detection of a range of conditions, while supporting a more personalized clinical approach for each patient.

To address this challenge, the project has a total budget of €1.7 million and brings together a consortium of five biomedical institutions: Navarrabiomed-Miguel Servet Foundation, Navarra University Hospital, Public University of Navarra, CIMA University of Navarra, and ADItech. It also includes four companies: insAIght, NUCAPS Technologies, Tairel Data, and TDN Advanced Traumatology and Rehabilitation Clinic. Altogether, nearly 70 healthcare professionals and researchers from complementary fields, including neuroscience, geriatrics, omics technologies, data processing and artificial intelligence, and nanotechnology development, are participating in the initiative.

Carmen, the study’s first centenarian participant

Carmen's home, located in the heart of Pamplona's Ensanche district, reflects the calm and warmth of a place where a long life has unfolded. Sitting in her favourite armchair is the first participant in the BIOANCIENT project. Carmen is 100 years old, although it is difficult to believe. Her voice retains a remarkable strength, and her lively eyes seem to defy the passage of time. “Oh, my dear boys” or “how lovely they are,” she says with the natural ease of someone who has never sought attention for herself.

It is not easy to summarise a century of life. Born in Palencia, she moved to Pamplona/Iruña with her parents at an early age. She was among the few women of her generation to pursue higher education away from home, studying in Zaragoza and Madrid at a time when this was still uncommon for women. She fondly recalls strolling through Plaza del Castillo with a group of friends they nicknamed “the witches,” sharing laughter and confidences. It was on one of those walks that she met Miguel, her future husband, with whom she enjoyed what she describes as “a marriage deeply in love.” Even today, speaking about him moves her emotionally.

Family has always been the centre of her life. She is the mother of 13 children, grandmother to 55 grandchildren, and great-grandmother to 101 great-grandchildren, the youngest of whom was born only a few days ago. Asked how she managed to raise such a large family, her answer is simple: “You have to give each child what they need and help them develop their potential.” She sums up the philosophy that guided her parenting with a phrase she still remembers fondly: “I made tunics with sleeves for all of them.”

Carmen accepts the challenges of ageing with serenity. She lives with dysphagia, which means she must eat puréed foods that, she admits, “are not as tasty as regular food.” She uses a walking frame, although she still protests when her son encourages her to rely on it more often around the house. Her greatest passion remains reading. She enjoys novels, essays, and, in recent years, biographies of Popes. She also uses a tablet and smartphone, “with patience,” mainly to view photos and listen to messages from family members spread across the world, but also to follow the occasional podcast.

When asked whether she would like to live another hundred years, she reflects for a moment before answering: “Every day that dawns is a gift. But without my children... no.” She would not want to live in a world in which her children were no longer by her side.

With the same generosity that characterises the way she speaks about her family, Carmen has agreed to participate in the BIOANCIENT project. To support the research, she has completed interviews, undergone assessments, and donated biological samples that will help advance scientific understanding of human longevity.

The research on the molecular diagnosis of cholangiocarcinoma through liquid biopsy in bile was conducted by investigators from Navarra University Hospital (HUN), CIMA, and Navarrabiomed through IdiSNA.

The study “Liquid Biopsy in Bile: A New Tool for the Molecular Diagnosis of Cholangiocarcinoma with Biliary Stricture,” presented by Dr. Jesús Urman of the Digestive Diseases Department at Navarra University Hospital (HUN), received the award for Best Basic Science Communication at the 29th National Meeting of the Spanish Association of Gastroenterology, recently held in Madrid.

The research was made possible through the multidisciplinary collaboration of investigators from HUN, CIMA (affiliated with CIBERehd), and Navarrabiomed, within the framework of the Navarra Institute for Health Research (IdiSNA).

The study describes the experience developed at Navarra University Hospital in the molecular diagnosis of bile duct cancer, or cholangiocarcinoma, using bile, a fluid produced in the liver and transported to the duodenum through the bile ducts. Cholangiocarcinoma is a highly lethal malignant tumor, partly due to its limited response to currently available chemotherapy and immunotherapy treatments.
Molecular profiling of tumor tissue is recommended to identify genetic alterations that may serve as therapeutic targets or actionable mutations, enabling the use of targeted therapies and advancing a Precision Medicine approach. Such treatments have the potential to improve outcomes for patients with cholangiocarcinoma.

The study’s findings demonstrate that molecular analysis of bile is more informative than tumor tissue analysis for identifying the mutations present in individual tumors.

Cholangiocarcinoma can cause a narrowing or biliary stricture, leading to the development of jaundice (yellowing of the skin and mucous membranes) due to bile stagnation. As a result, bile becomes enriched with tumor-derived products. In these cases, bile drainage is required through the placement of a biliary stent using a procedure known as endoscopic retrograde cholangiopancreatography (ERCP).
The researchers’ approach involved performing molecular analysis of this retained bile using next-generation sequencing (NGS) technologies. Collecting the stagnant bile through aspiration is a simple, quick procedure that does not pose any additional risk to the patient.

Advantages for Mutation Detection and Targeted Therapy Selection

The study included 25 patients with cholangiocarcinoma and biliary stricture who underwent ERCP at HUN, representing the largest paired bile-tissue sample series reported to date.

Analysis of bile detected mutations in 100% of cases, compared with 84% through tumor tissue analysis. Furthermore, bile analysis identified 91% of all detected mutations, nearly twice the proportion identified through tissue analysis (48%). Most notably, NGS analysis of bile enabled the identification of seven patients (28%) carrying actionable mutations or therapeutic targets, whereas no patients (0%) were identified through tissue analysis alone. This means that bile analysis identified seven patients who could potentially benefit from targeted therapies and who would otherwise not have been recognized if only tissue samples had been analyzed.

The authors propose conducting a future national and international multicenter study to validate these findings, with the ultimate goal of implementing this approach in routine clinical practice.

Among the co-authors of the study are Jesús Urman, María Rullán, and Juan José Vila from HUN; Daniel Oyón from Reina Sofía Hospital (HRS); Matías Ávila, Carmen Berasáin, and María Arechederra from CIMA; and Javier Rández-Garbayo, David Guerrero-Setas, and Ana Purroy from Navarrabiomed.

On 29 April, Navarrabiomed hosted the second technical meeting with the Fast Green Consortium (UTE Fast Green), comprising representatives from the technology research and development center Tecnalia, Applus+ Laboratories, and Vivotecnia Research, the entity awarded the contract for the INNOVAP3M Innovation Procurement Project. The meeting, organized by Navarrabiomed’s Innovation Service, was also attended by María Ángeles Montes, Head of the Innovative Public Procurement Section at the Directorate-General for Science, Technology and Innovation of the Government of Navarre, as well as professionals from Science & Innovation Link Office (SILO), which serves as the project’s Technical Office.

The meeting began with a visit to the laboratories of the Oncoimmunology Unit and the Proteomics Scientific-Technical Service. During the visit, the heads of these units, David Escors and Joaquín Fernández, presented their main research activities, the equipment available in their facilities, and the services they provide to research teams and healthcare professionals within the Navarre Health Service (Servicio Navarro de Salud-Osasunbidea), as well as to other institutions and companies.

Progress in Platform Design

The project is currently in the initial phase of designing a platform for the production of clinical-grade small molecules. During the meeting, the Fast Green Consortium presented the progress achieved so far, along with upcoming milestones and development phases. Key topics discussed included the extraction and purification process for oleuropein, where participants reported that potential sources of raw materials had been successfully identified. Technical aspects of the pharmaceutical formulation were also reviewed. The description of critical material attributes, critical process parameters, and the control strategy for the pharmaceutical product were reported to be at an advanced and well-established stage of development.

The meeting also provided an opportunity to further define the strategy for regulated preclinical development, identify the cell lines to be used in in vitro studies, discuss techniques for characterizing the molecule’s mechanism of action, and advance the definition and design of in vivo efficacy models.

More Information About INNOVAP3M

INNOVAP3M is being developed within the framework of the Innovation Procurement Promotion Line (FID), launched by the Spanish Ministry of Science, Innovation and Universities, and is co-funded by the European Regional Development Fund (ERDF) under Spain’s 2021-2027 Multi-Regional Programme. The project has a total budget of €5 million, including €2 million in ERDF co-funding awarded through the Ministry of Science, Innovation and Universities.

One of the project’s main objectives is the development of a platform capable of producing clinical-grade small molecules under quality and purity conditions that ensure their safety for subsequent use in clinical trials. To validate this platform, the project has selected oleuropein as its use case. This choice is based on research carried out by Navarrabiomed’s Oncoimmunology Group, which has demonstrated the molecule’s effectiveness in patients treated with PD-1/PD-L1 checkpoint inhibitor immunotherapies.

Researchers from the Exercise, Health, Metabolism and Functional Capacity (EFIT) Group at the Public University of Navarra (UPNA) and Navarrabiomed have found that good cardiorespiratory fitness (commonly referred to as aerobic fitness or endurance) is associated with a lower prevalence of depressive symptoms in female university students, regardless of their body fat levels. The study, published in the Elsevier journal Mental Health and Physical Activity, analyzed data from 251 female university students with a mean age of 20.6 years. The results showed that nearly one in three participants presented clinically relevant depressive symptoms. Furthermore, the study found that the combination of low physical fitness and high body fat percentage doubled the likelihood of experiencing such symptoms.

The research was conducted by Mikel Gutiérrez García, Sergio Oscoz Ochandorena, Mikel Izquierdo Redín, and Robinson Ramírez Vélez, the latter two serving as senior authors. To carry out the study, the team employed gold-standard methods for assessing body composition and physical fitness. Body fat was measured using dual-energy X-ray absorptiometry (DXA), while cardiorespiratory fitness was assessed through a cardiopulmonary exercise test on a cycle ergometer (a medically adapted stationary bicycle), which directly measures maximal oxygen uptake (VO₂max). Depressive symptoms were evaluated using the CES-D-10 scale, an internationally validated screening tool.

Thirty Percent Showed Relevant Depressive Symptoms

The findings confirm the considerable mental health burden within this population. Thirty percent of the students assessed exceeded the clinical threshold for depressive symptoms. In addition, 61% had a high body fat percentage, defined as 32% or higher, despite having a body mass index (BMI) within the range generally considered normal.

According to the research team, this result highlights “the limitations of body mass index (BMI) as a sole indicator of health in young women.” BMI relates weight to height but does not distinguish between fat mass, muscle mass, and other body components, which means it may fail to detect excessive adiposity in individuals whose body weight appears normal.

Participants were classified into four groups according to their body fat percentage and aerobic fitness levels. This classification followed the internationally recognized “fat-but-fit” model, a term used to describe individuals who have excess body fat but maintain good physical fitness.

The analysis revealed a clear pattern. Students with high adiposity and low fitness levels recorded the highest depressive symptom scores and were twice as likely to present clinically relevant depressive symptoms compared with the reference group, which consisted of participants with low adiposity and good physical fitness.

By contrast, students with high adiposity but good cardiorespiratory fitness did not show significant differences compared with the reference group. According to the researchers, this finding suggests that “good physical fitness may buffer the potential negative psychological effects associated with excess body fat.”

“The main finding is that what defines the highest-risk group is neither body fat alone nor low fitness in isolation, but the combination of both,” explains Mikel Izquierdo. “This changes the preventive approach: improving physical fitness can be a very powerful protective tool for mental health, even when body weight does not change.”

Implications for University Public Health

According to the authors, the study offers two methodological advantages over previous research. First, it uses objective and direct measurements, such as DXA scans and cardiopulmonary exercise testing with gas analysis, rather than estimates based solely on BMI or physical activity questionnaires. Second, it focuses on a relatively understudied population facing an increasing burden of mental health challenges: young women attending university.

“The transition to university coincides with a critical period from hormonal, social, and academic perspectives, increasing vulnerability to mood disorders, particularly among women,” says Robinson Ramírez, the study’s principal investigator. “Our data suggest that promoting improvements in aerobic fitness within this population could represent an accessible, low-cost, and non-pharmacological strategy to support mental health.”

Among the possible biological mechanisms underlying this association, the researchers note that physical exercise may help reduce systemic inflammation, stimulate factors linked to brain health, and improve regulation of the autonomic nervous system, which plays a key role in the body's response to stress. On a personal and social level, exercise may also help students feel more capable, strengthen confidence in their own abilities, and improve their relationship with their body image.

The study’s authors believe that universities can play an important role in mental health prevention and support by implementing structured physical fitness promotion programs. According to the research, such initiatives could be integrated into university well-being policies as an accessible, evidence-based strategy for enhancing student mental health

The programs analyzed in her dissertation showed, above all, improvements in skills related to object control.

Learning to run, jump, or throw a ball is part of every child’s development during the early years of life. These abilities, known as fundamental motor skills, facilitate participation in games, physical activities, and sports, and can help children maintain an active lifestyle from an early age. A doctoral dissertation defended at the Public University of Navarre (UPNA) examined how factors such as family, teachers, schools, and the wider environment influence the development of these skills in children aged 4 to 6 years. The research, conducted by Loreto Alonso Martínez (Oviedo, Asturias, 1992), a graduate in Physical Activity and Sport Sciences, concludes that interventions implemented through schools and communities can help improve certain motor skills, particularly those related to object control, such as throwing, catching, bouncing, or dribbling a ball.

One of the studies included in the dissertation analyzed different programs designed to improve children’s daily lifestyle habits. These initiatives focused not only on increasing physical activity but also on reducing sedentary time and promoting adequate sleep.

The findings show that this type of program, which acts in a coordinated manner on students, families, and the school environment, is effective in improving fundamental motor skills, especially those requiring object control. These include common actions found in many children's games, such as throwing, catching, bouncing, or striking a ball. By contrast, the effects were more limited in other areas, such as overall physical fitness or changes in the broader set of behaviours related to physical activity, sedentary lifestyles, and sleep.

A Reference Framework for Assessing Motor Development

The dissertation also established reference values for assessing motor skills among Spanish children. To do so, more than 200 schoolchildren completed a series of tests. These activities evaluated, for example, whether they could maintain balance, jump, roll, move, throw a ball, or catch it. The results confirmed that these tests are suitable for evaluating children in Spain and made it possible to establish age- and sex-specific reference values.

“The results showed better performance among boys in object-control tasks, whereas similar outcomes were observed between boys and girls in the other dimensions, along with a progressive improvement with age,” explains Loreto Alonso.

Memory, Attention, and Impulse Control

Another study included in the doctoral dissertation examined certain mental abilities that help individuals pay attention, remember instructions, control impulses, and adapt to new situations, collectively referred to as executive function. These abilities are necessary, for example, to wait for one’s turn, follow the rules of a game, remember a sequence of movements, or change strategy when an activity does not go as expected. The research assessed children between 3 and 7 years of age.

“The results show progressive cognitive development with age, as well as sex-related differences, with girls performing better, particularly in inhibitory control, which is the ability to regulate impulses and avoid automatic responses,” the researcher notes.

The Influence of Parents

The final part of the dissertation examined whether parents’ physical activity levels and physical fitness were related to their children’s motor development and lifestyle habits. The results indicate that a child’s age and sex explain differences in motor skills and physical fitness better than their parents’ level of physical activity. However, the study found that better maternal physical fitness was associated with some healthier childhood routines, including better sleep quality and higher levels of physical activity.

“This dissertation highlights that, although the family plays an important role, motor development and the adoption of healthy habits during childhood depend largely on strategies focused on the school and community environment,” says Loreto Alonso. “In this regard, it is essential to guarantee equitable motor opportunities within the educational context.”

Loreto Alonso carried out her research within the Exercise, Health, Metabolism and Functional Capacity (E-FIT) Research Group at Navarrabiomed, the biomedical research center jointly supported by UPNA and the Government of Navarre. The dissertation was supervised by two faculty members from the university: Professor Mikel Izquierdo Redín, head of the E-FIT group, and Associate Professor Alicia Alonso Martínez, director of the Observatory of Physical Activity among Schoolchildren in Navarre. The dissertation was completed under the International Doctorate program.

• More information.

• The Carmen Delgado/Miguel Pérez-Mateo Fellowships are the largest privately funded pancreatic cancer research program in Spain.

Jesús María Urman Fernández, Head of the Biliopancreatic Pathology Section at the University Hospital of Navarra (HUN) and researcher at Navarrabiomed, has been awarded one of the two grants granted in the 11th edition of the Carmen Delgado/Miguel Pérez-Mateo Fellowships, considered the largest private funding program for pancreatic cancer research in Spain. The Clinical Research Fellowship, worth €120,000, will support a research project focused on developing an innovative tool to improve the detection of molecular alterations in pancreatic cancer patients through the analysis of tumor DNA present in bile.

The fellowships are promoted by the Pancreatic Cancer Association (ACANPAN), the Spanish Pancreatology Association (AESPANC), and the Spanish Gastroenterology Association (AEG). They are funded primarily through resources raised by the Run of the Cities Against Pancreatic Cancer initiative.

The project led by Urman aims to identify molecular alterations through a liquid biopsy performed on bile samples. This strategy could increase the detection of actionable mutations and facilitate patients’ access to targeted therapies, thereby supporting a more personalized and precise approach to treatment.

“This fellowship represents a major boost to the multidisciplinary work we carry out at the University Hospital of Navarra in collaboration with Navarrabiomed and with the participation of professionals from Cima. Our goal is to implement a non-invasive procedure that allows us to identify more molecular alterations and facilitate patients’ access to targeted treatments. In addition, this procedure would eliminate the need to obtain histological samples and would not entail additional risks for patients,” emphasized Urman.

In addition to the grant awarded to Jesús Urman, the program’s Basic Research Fellowship, also worth €120,000, was awarded to Juan Dubrot Armendáriz, Principal Investigator of the Tumor Evasion and New Targets Group at Cima University of Navarra.

Twenty Projects Funded Since 2015

Since their creation, the Carmen Delgado/Miguel Pérez-Mateo Fellowships have allocated €1,461,000 to fund 20 high-level scientific research projects related to pancreatic cancer. The primary source of funding is the Run of the Cities Against Pancreatic Cancer, a charitable initiative launched in 2015 with the aim of raising funds for research into a disease that continues to present significant unmet medical needs.

According to current estimates, more than 10,400 people will be diagnosed with pancreatic cancer in Spain during 2026. With a five-year survival rate of less than 10% and a steadily increasing incidence, research remains the key pathway toward earlier diagnosis and the development of new treatments.

• The Kick-Off meeting of the THERESA PCP project was held on the 22nd and 23rd of September, in Pamplona (Spain). 
   

The THERESA PCP is a 4-year EU-funded Pre-Commercial Procurement project (PCP) aimed at developing a “green” and innovative solution to treat Hospital Wastewater. Through its structured PCP process, the THERESA PCP project brings together public buyers and innovators to co-develop an integrated, “green,” and scalable technology. In doing so, it addresses a critical environmental and health challenge while helping European healthcare systems move towards greater sustainability, safety, and resilience.

Hospitals produce wastewater containing a complex mix of pharmaceuticals, disinfectants, pathogens, and hazardous substances, making it a hotspot for the spread of antimicrobial resistance. Traditional municipal treatment plants are not designed to fully remove these pollutants, which underlines the need for tailored and effective solutions.  Dealing with HWW and healthcare waste in a way that can minimize potential risks for local populations is one of the greatest challenges faced by healthcare facilities. 

The project brings together 16 partners from 6 European countries (Belgium, Estonia, Greece, Poland, the Netherlands and Spain), all with high expertise in different disciplines within healthcare sector. 

• The procurer’s group is composed of 7 healthcare organisations (Ziekenhuis aan de stroom, Sihtasutus pohja-eesti regionaalhaigla, Wojewodzki Szpital Specjalistyczny Wolsztynie, Fundación Pública Miguel Servet, Servicio Andaluz de Salud and Consorci Hospitalari de Vic) and 2 affiliated entities (Fundación Pública Andaluza Progreso y Salud and Universiteit Maastricht). 
• The supporting organisation’s group is composed of 6 entities (Science & Innovation link office, Ticbiomed, Science Union for Innovation, Corvers Procurement Services, Instytut Ekologii Terenow Uprzemyslowionych and Health Care Without Harm Europe) and 1 affiliated entity (Corvers Greece Monoprosopi), with a wide range of expertise in legal, management, and Open Market Consultation, among others.

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By fostering collaboration across countries and sectors, the THERESA PCP project sets a solid foundation for innovative solutions that will strengthen both environmental protection and the resilience of European healthcare systems.