Noticias

Miren Altuna Azkargorta, a predoctoral researcher at Navarrabiomed’s Neuroepigenetics Unit, will defend her doctoral dissertation for the Universidad Pública de Navarra on Thursday, January 14. The defense will take place via videoconference and with limited attendance at 12 noon in the Navarrabiomed assembly hall (only people with prior authorization are permitted to attend the event in person). While preparing her dissertation, “Identification of epigenetic biomarkers in Alzheimer’s disease,” Miren Altuna was supervised by Maite Mendioroz Iriarte, a Navarrabiomed researcher and neurologist at the Hospital Complex of Navarre, and CHN internist Gregorio Tiberio López, her dissertation advisor.

Alzheimer’s disease (AD) is a neurodegenerative disease and the most common cause of dementia. In the last few decades, its prevalence has increased as a result of the aging population. AD is a multifactorial disease in that both genetic and environmental risk factors contribute to the disorder, although its pathogenesis is not yet fully understood. The study of epigenetics therefore plays a key role. Epigenetic mechanisms, which are partially inherited but can also be altered by environmental factors, modify gene expression without changing the DNA sequence.

The work of Miren Altuna aims to identify a footprint of DNA methylation (the most widely studied epigenetic mechanism) typical of AD by using the human hippocampus, an area of the brain that is particularly affected by the pathogenic mechanisms of AD. To achieve this, different strategies were used: (1) The study of DNA methylation changes by means of the genome-wide strategy, and (2) The study of changes in the methylation pattern for a given gene, in this case the PLD3 gene (it has previously been reported that a polymorphism of this gene increases the risk of developing AD).

The findings included identification of a differentially methylated pattern affecting the genes involved in neurogenesis in the hippocampus and differential methylation of the alternative promoter region of the candidate gene PLD3. It has been hypothesized that changes in DNA methylation could contribute to alterations in the regulation of neurogenesis previously described in the hippocampus of subjects with AD and that the risk conferred by the PLD3 gene in the development of AD may be related to changes in its epigenetic regulation.

The results presented support the existence of a specific epigenetic footprint of AD that could potentially be useful as a source of diagnostic and/or prognostic biomarkers and could therefore lead to progress in the knowledge of the pathogenesis of AD and the potential identification of future therapeutic targets. These findings have been published in three articles in indexed journals: Clinical Epigenetics (https://doi.org/10.1186/s13148-019-0672-7 and https://doi.org/10.1186/s13148-018-0547-3) and Neurología.

Miren Altuna also made her doctoral work public at the 2017 and 2019 international congresses of the European Academy of Neurology and at the 69th annual meeting of the Spanish Society of Neurology in 2017.

Pedro Dorado, a predoctoral researcher at Navarrabiomed’s Microbial Pathogenesis Unit - IdiSNA, will defend his doctoral dissertation for the Universidad Pública de Navarra via videoconference at 11:00 a.m. on Friday, January 8, in the Navarrabiomed assembly hall (only people with prior authorization are permitted to attend the event in person).

The dissertation, “Genetic tools derived from Staphylococcus aureus for the development of biotechnological applications in gram-positive bacteria,” was prepared at Navarrabiomed under the supervision of Iñigo Lasa Uzcudun, director of the center and principal investigator in the Microbial Pathogenesis Unit, and Cristina Solano Goñi, a researcher in the same unit.

Staphylococcus aureus intermittently colonizes the skin of 20% of adults. Under certain circumstances, bacteria cross the epithelial barrier and reach the internal organs, where they become a highly versatile pathogen with the capacity to cause a range of problems, including mild infections (boils and abscesses) and very serious diseases such as endocarditis, osteomyelitis, pneumonia and toxic shock syndrome. As part of this dissertation, Staphylococcus aureus virulence factors were used to develop biotechnological tools applicable to gram-positive bacteria.

In the first chapter, elements used by Staphylococcus aureus to adhere to tissues and medical implants were used to enhance the biotechnological capabilities of the environmental bacterium Rhodococcus erythropolis. The second chapter of the dissertation focuses on the study of the evolution of mobile genetic elements known as plasmids to understand how antibiotic resistance genes are maintained and spread when the antibiotic is not present. Finally, the third chapter concerns phage therapy and focuses on the development of defective phages carrying a CRISPR-Cas9 system aimed at the destruction of antibiotic-resistant Staphylococcus aureus strains.

The research results have been published in the journal Microbial Biotechnology and have been presented at several scientific forums: the 12th Molecular Microbiology Meeting, the 7th Congress of European Microbiologists (FEMS) and EUROBIOFILMS 2019.

To prepare his dissertation, Pedro Dorado received a grant from the National Research Personnel Training Program (FPI) in the 2015 call for applications, as well as funding from the Universidad Pública de Navarra for scientific and technical research projects.
 

Sonia Sáenz Lahoya, a predoctoral researcher at Navarrabiomed’s Microbial Pathogenesis Unit - IdiSNA, will defend her doctoral dissertation for the Universidad Pública de Navarra (UPNA) via videoconference at 10:30 a.m. on Thursday, December 17, in the center’s assembly hall. Only people with prior authorization are permitted to attend in person.

The dissertation, “Noncontiguous operons: a new strategy to coordinate gene expression in bacteria,” was prepared at Navarrabiomed under the supervision of Iñigo Lasa Uzcudun, director of the center and principal investigator in the Microbial Pathogenesis Unit.

In bacteria, genes that code for proteins involved in the same biological process are often grouped into operons, which are coordinately regulated transcription units in bacteria. The genes of an operon are transcribed into a single polycistronic mRNA molecule, which codes for more than one protein under the control of the same promoter. This organization provides an efficient mechanism for coordinating the expression of functionally related genes and is the basis for gene regulation in bacteria.

This dissertation demonstrates the existence of a higher level of organization in the structure of the operon, known as a noncontiguous operon. It consists of an operon that contains a gene or genes that are transcribed in the opposite direction to the rest of the operon. This new transcription architecture is exemplified by the menE-menC-MW1733-ytkD-MW1731 genes, which are involved in the synthesis of menaquinone (an antihemorrhagic vitamin) in Staphylococcus aureus.

The results indicate that the menE-menC-ytkD-MW1731 genes are transcribed as a transcription unit, while the MW1733 gene, located between menC and ytkD, is transcribed in the opposite direction. This genetic organization generates overlapping transcripts whose expression is regulated through ribonuclease III-mediated processing and a transcriptional interference mechanism.

In light of these results, the classical view of the structure of operons must be revised to take account of this new operon arrangement in which cotranscription and overlapping transcription combine to coordinate functionally related gene expression.

The conclusions of the project have been published in the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America). 

To carry out this research, Sonia Sáenz received a Research Personnel Training grant from the Ministry of Science.
 

Miren Vallejo Ruiz, a predoctoral researcher in the Navarrabiomed Hematological Oncology Unit – Navarre Health Research Institute (IdiSNA), will defend her doctoral dissertation from the Universidad Pública de Navarra on Tuesday, 17 November at 11 a.m. The event will be held in the Navarrabiomed Assembly Hall. Due to current COVID-19 restrictions, attendance is limited, but a videoconference of the defense will be available.

The dissertation, “Evaluation of functional immune response developed against cytomegalovirus, Epstein-Barr virus and adenovirus and their regulatory elements in allogeneic hematopoietic stem cell transplantation recipients,” was developed at Navarrabiomed under the direction of Natalia Ramírez Huerto, Head of the Hematological Oncology Unit.

Research focused on describing the main biological and genetic variables that affect the development of a protective immune response to infections caused by cytomegalovirus (CMV), Epstein-Barr virus (VEB) or adenovirus (AdV) in patients who have received an allogeneic hematopoietic stem cell transplantation (allo-HSCT), i.e., those requiring the administration of healthy stem cells to increase bone marrow function.

One of the results of this study shows that the analysis of the functionality of the subpopulation of virus-specific T cells in patients who have received an allo-HSCT can be used to predict CMV infection in the post-transplantation period. T cells help destroy tumor cells and control immune responses.

With regard to the parameters that regulate the workings of this immune response, the study also used samples from healthy donors to show that gliotoxin (GT), the fungal toxin in Aspergillus fumigatus (AF), inhibits the function of subpopulations of T cells and natural killer (NK) cells, whose mission is to destroy infected cells and cancer cells, and to regulate immune responses.

In vitro observations also confirmed that the presence of GT in combination with the drugs ciclosporin A and methotrexate triggers a mechanism that impedes immune response. These drugs are used as a prophylactic against graft-versus-host disease (GvHD) in these patients. This experimental result was corroborated in patients after HSCT, when the presence of bis-methyl-gliotoxin (bmGT), the GT metabolite, in combination with the administration of cyclophosphamide, negatively modulated specific immune response against CMV/VEB/AdV.

Finally, the study confirmed that that the evaluation of certain polymorphisms in cytokine and chemokine genes and their receptors in patients and their respective donors can be used to predict the individual risk of developing CMV infection after HSCT. Analysis of these polymorphisms was used to generate an equation and a practical score for early identification of patients with a high risk of CMV infection after allo-HSCT.

These results were presented at three events: the International Conference of the European Society for Clinical Cell Analysis held in Valencia in September 2018, the 24th Congress of the European Hematology Association held in Amsterdam in June 2019, and the 61st National Conference of the Spanish Society of Hematology and Hemotherapy (SEHH/SETH) held in Valencia in October 2019. The research study was also on display in October 2020 at the 62nd edition of the SEHH/SETH conference. 

In order to prepare her dissertation, Miren Vallejo was a beneficiary of the Government of Navarre’s 2017-2019 Industrial Doctoral Students financial aid program, issued in 2016, for research and knowledge-sharing companies and organizations to hire doctoral students. While preparing her dissertation, Miren Vallejo also participated in an internship from June to December 2018 in the group “Genetic and clinical analysis of hematological neoplasms and stem cell transplantation” at Gregorio Marañón General University Hospital.
 

Marina Iridoy Zulet, a neurologist trained at the Hospital Complex of Navarre (CHN) and a predoctoral researcher in the Navarrabiomed associated research group Neuromuscular Disease and Motor Neuron Disease, will read her doctoral dissertation in the School of Health Sciences lecture hall at the Universidad Pública de Navarra (UPNA) at 12 noon on Thursday, 12 November. Marina Iridoy currently forms part of the neurology team at Zumarraga Hospital.

Her dissertation, “ProtALS Study: Proteomic analysis of postmortem tissue of subjects with amyotrophic lateral sclerosis. The search for biomarkers and therapeutic targets,” was developed at Navarrabiomed under the direction of Ivonne Jericó Pascual, a specialist doctor in the CHN Neurology Service and a Navarrabiomed associate researcher, and Joaquín Fernández Irigoyen, the coordinator of the Proteomics Platform and a researcher in the Navarrabiomed Clinical Neuroproteomics Unit – Navarre Health Research Institute (IdiSNA). Due to current COVID-19 restrictions, attendance is limited, but a videoconference of the defense will be available.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Diagnosed patients have a life expectancy of three to five years. Its prevalence in Navarre is 6.2 cases per 100,000 inhabitants per year. Unfortunately, no biomarkers of the disease have been identified to allow for early diagnosis. After the first symptoms appear, diagnosis can sometimes take up to 12 months. Treatments to effectively cure the disorder are also currently unavailable.

In her dissertation, Marina Iridoy performed exhaustive proteomic analysis of postmortem neurological tissue of people with ALS. The goal was to obtain a panel of possible biomarkers of the disorder that could then be analyzed in the blood serum of patients with a clinical diagnosis of ALS in order to validate them as possible biomarkers of the disease.

The study results were published for a meeting of the European project Network to Cure ALS (ENCALS) and in the journal International Journal of Molecular Sciences.

This project began in 2015 thanks to the Ice Bucket Challenge fundraising campaign led by the Association of Patients with Amyotrophic Lateral Sclerosis and Family Members in Navarre (ANELA) with the aim of increasing our knowledge of the disorder.

Navarrabiomed se suma un año más a las actividades de las Semanas de la Ciencia, la Tecnología y la Innovación de Navarra 2020, evento de divulgación científica que tendrá lugar entre el 9 y al 21 de noviembre de 2020.  Se celebrarán numerosas actividades para acercar la ciencia a la ciudadanía: conferencias, talleres, mesas redondas, puertas abiertas, espectáculos, entre otros. Debido a la situación actual de pandemia por la Covid-19, muchos de los eventos serán online y, los que son presenciales, se realizarán bajo las normas de seguridad establecidas para prevenir la infección del virus, como el aforo limitado y el uso de mascarilla.

En esta edición Navarrabiomed ha programado dos webinar para divulgar la actividad del centro de investigación biomédica:
 

• Miércoles, 18 de noviembre, 16:30 h. Investigación biomédica. Conoce en este webinar cuáles son los pasos necesarios para dedicarte a la investigación, una salida profesional apasionante y de máxima actualidad. Intervendrán Iñigo Lasa Uzcudun, Director de Navarrabiomed, María Apellániz Ruiz, Investigadora de la Unidad de Medicina Genómica de Navarrabiomed e Imanol Arozarena Martinicorena, Investigador Principal de la Unidad de Señalización en Cáncer de Navarrabiomed.
  
  Sesión online vía zoom exclusiva para alumnado de Bachillerato de Ciencias, FP o grados universitarios. Requiere inscripción previa desde la web de Navarrabiomed (hasta las 15:00 h. del miércoles, 18 de noviembre). Se enviará enlace directo e ID/contraseña al email facilitado.
   
• Jueves, 19 de noviembre, 18:30 h. Del ensayo clínico al medicamento que nos recetan. Conoce en esta sesión el proceso integral del desarrollo de un fármaco. Interviendrán Ruth García Rey,  Responsable Área Clínica de la Plataforma de Ensayos Clínicos de Navarrabiomed, Eva Zalba Garayoa, Responsable Área de Gestión de la Plataforma de Ensayos Clínicos de Navarrabiomed y Patricia Fanlo Mateo, Facultativa Especialista de Area del Servicio de Medicina Interna del Complejo Hospitalario de Navarra.
  
  Sesión online vía zoom para cualquier persona interesada. Requiere inscripción previa desde la web de Navarrabiomed (hasta las 15:00 h. del jueves, 19 de noviembre). Se enviará enlace directo e ID/contraseña al email facilitado.

• The work was carried out within the framework of ICTUSnet, a European project for interregional collaboration promoting innovation and improved healthcare for stroke patients.

María Herrera Isasi, a neurologist in the Stroke Unit at the Hospital Complex of Navarre (CHN) and the coordinator of the ICTUSnet project in Navarre (which is done at Navarrabiomed), and Silvia Astráin Mendoza, the project leader at the Brain Injury Association of Navarre (ADACEN), gave a press conference today at Navarrabiomed on the conclusions of a multidisciplinary study on sharing clinical decision-making in the healthcare process of stroke patients. This initiative was implemented within the framework of ICTUSnet, a European project for interregional collaboration for innovation and improved healthcare for stroke patients. The speakers were accompanied by Marta Ancín Pagoto, CHN Director of Healthcare Services.

The press conference was held today in commemoration of World Brain Injury Awareness Day and World Stroke Day, which is Thursday, October 29. Stroke is the primary cause of brain injury.

Consensus between professionals and patients

Sharing clinical decisions implies the use of a relationship model between healthcare professionals and patients throughout the diagnostic process and therapy. It also involves the need to keep patients informed during the different healthcare stages and empower them by giving them an active role to play. This kind of decision-making is in line with patient-centered medicine in its aim to provide more humane care. It also involves two-way communication rather than one-sided release of information, and it has been demonstrated that patients adhere better to the chosen procedure.

María Herrera explained what this model involves in healthcare practice. “As professionals, we’re aware that it’s our obligation to inform patients about the procedures available to prevent, diagnose and treat specific health problems, including the different options, their goals and possible consequences. And we do all this by using informed consent forms and providing information during interviews. But now we are going one step further. The idea is to ensure that decision-making includes the other side, namely, the life goals, values, priorities and needs specific to the patient, who, in this case, is a stroke patient or someone at risk of suffering from a stroke, as well as the patient’s family members or representatives, to reach a firm decision together that considers both sides with the active participation of the patient,” she said. She also highlighted the fact that this new model represents a change in the form of communication, which means that professionals will need training, as well as new tools to provide support for ICTs and audiovisual information, along with a commitment from the public authorities to promote this model with patient-centered work areas, as well as models of interdisciplinary action and teamwork.

From this global perspective, the study analyzed the current status of the model of sharing clinical decision-making in the stroke care process in the Navarre Health Service – Osasunbidea. The study involved organizing, in collaboration with ADACEN, four focus group meetings in February and March (prior to the pandemic) made up of representatives of all stakeholders involved: patients, family members, professionals in neurology, neurorehabilitation, primary care and social work, as well as management professionals from the Navarre Ministry of Health, among others.

Silvia Astráin was pleased with how the sessions went. She said, “We were able to provide a place for people to reflect on the topic, share experiences, point out uncovered needs and existing barriers, and identify the areas of healthcare that can be improved.” The ADACEN association, which helps people with acquired brain injury and their families, has been fighting to ensure patients receive the best care since it was founded in 1994. ADACEN officials are therefore pleased that time is being spent to listen to the opinions and needs of patients and their family members so that changes can be made to the process.

Marta Ancín stressed the importance of collaborative work between professionals to promote comprehensive patient care. She also brought up the commitment made by the Navarre Ministry of Health when it implemented its Humanization Strategy of the public health system in 2017. “Despite the delicate experience we are living through, these actions and projects should be maintained to make progress on and improve patients’ satisfaction with the treatment they receive,” Ancín said.

The press conference ended with some words from Iosune Etxebeste Arretxea, a stroke patient, and Pilar Seminario Alonso, a family member. Both participated in the focus groups and wanted to provide a face for all those people who live with the effects of a stroke or who are caregivers or companions.

Educational video and documents

Anyone interested in finding out more about this study on sharing clinical decision-making can consult the technical documentation on the conclusions, the video Working Together on Stroke Care Strategies, and the guidebook for patients and family members.
All these actions fall within the framework of the ICTUSnet Project, which forms part of the Interreg Sudoe Program, an initiative financed by the European Regional Development Fund (ERDF). The mission of ICTUSnet is to create a collaboration network of different Southern European regions made up of patients and professionals working in different stroke-related areas. At the same time, the project aims to create research infrastructure that draws on innovative data analysis technologies to improve comprehensive stroke care systems and reduce the impact of the disease on the population.

Information webinar on the occasion of World Stroke Day

The CHN Stroke Unit team invites all those interested to participate in the webinar “Stroke and COVID-19” on Thursday, October 29 at 4 p.m. Professionals from the CHN, primary care, ADACEN and the Ubarmin Clinic will participate by providing information on how COVID-19 has affected the process of stroke and acquired brain injury in Navarre. Information will also be presented on how healthcare and association resources have been adapted to continue providing care to patients at all stages (including primary care, preventive measures, hospital care, neurorehabilitation and social health resources).
 

Beatriz Rapún Araiz, a predoctoral researcher in Navarrabiomed’s Microbial Pathogenesis Unit - IdiSNA, will read her dissertation for the Universidad Pública de Navarra (UPNA) on Tuesday, October 27, 2020. The defense will take place at 11 a.m. in the Navarrabiomed assembly hall. Due to current COVID-19 regulations, attendance is limited, but a videoconference of the reading will be available.

The dissertation, “Characterization of the two-component sensorial network of Staphylococcus aureus”, was prepared at Navarrabiomed under the direction of Iñigo Lasa Uzcudun, the Director of the center and head of the Microbial Pathogenesis Unit.

Bacteria’s ability to adapt to new environmental conditions is controlled by two-component systems (TCSs). Although highly detailed knowledge about how each TCS works and the function it performs has been acquired in recent years, our knowledge is still limited regarding global aspects of the network, such as the overlap between the signaling pathways of each TCS and its specific purpose.
In her dissertation, Rapún uses a unique genetic tool developed in the laboratory to reconstruct the complete TCS regulon (collection of genes or operons controlled by the same regulatory protein) in a living cell. She also studied how the presence or absence of the TCS affects bacteria biology and speciation (the process of formation of new species) of the genus Staphylococcus. Finally, the dissertation discusses and assesses new therapeutic strategies against the TCSs of Staphylococcus aureus.

This dissertation led to the publication of three scientific articles in the journals mSystems, published by the American Society for Microbiology, Current Opinion in Microbiology and Scientific Reports.

The results were also made public at four conferences, two of which were organized by the Molecular Microbiology group of the Spanish Society of Microbiology and held in Seville (2016) and Zaragoza (2018). In 2017, the research study was also presented in Valencia as part of the international conference organized by the Federation of European Microbiological Societies (FEMS), and in 2019, it was presented in a course of the European Molecular Biology Organization (EMBO) in Spetses (Greece).

To carry out the research study, Rapún received a training grant as a UPNA research staff member to complete her doctoral dissertation.
 

• The projects are funded with €108,104 from the Regional Government of Navarre’s Ministry of Universities, Innovation and Digital Transformation within the framework of the inDemand Navarre initiative

On September 28, 2020, Agurtzane Martínez Ortigosa, the Director General of Innovation of the Government of Navarre, approved the results of the first call for “inDemand Navarre: Demand-Driven Innovation in Health” grants, in which ICT companies were selected to offer their digital services to address the challenges posed by teams at the Navarre Health Service – Osasunbidea (SNS-O).

The four companies selected (iAR, Consultoría Informática Adhoc, TedCas and Desarrollos ANASINF) have relevant experience in the development of industrial and business solutions, which they will now apply to the health industry. They were awarded a total grant amount of €108,104 to start up four innovative tools designed to cover priority healthcare needs.

Innovative Joint Development Process

The solutions will be implemented in an eight-month joint development process in which the health professionals who detected the specific need will work in cooperation with high-tech firms. This innovative approach within the framework of the inDemand Navarre model is promoted by the Navarre Ministry of Universities, Innovation and Digital Transformation and the Navarre Ministry of Economic and Business Development through the European Center for Business Innovation of Navarre (CEIN) and the Navarre Development Company (Sodena). The Navarrabiomed Innovation Support Unit and the Navarre Ministry of Health also help coordinate the inDemand model among all the institutional agents of Navarre.

Potential users of each application will become involved in the process in coming months. The ultimate goal is to obtain functional prototypes that can be validated in real contexts and then included in the SNS-O to benefit patients.

Kick-Off Meetings

In the first half of October, the companies had the first kick-off meetings with the participating teams of healthcare professionals in order to define the technical specifications of the solutions in greater detail, which necessarily involved the transfer of specialized knowledge from the professionals to the companies.

Industrial Augmented Reality (iAR) will develop the ConectaSOS solution with Fermina Beramendi, a doctor in the Outpatient Emergency Service, who participates in representation of professionals from advanced life support ambulances (ALS ambulances), SOS Navarra and Emergency Services at the Hospital Complex of Navarre (CHN). This initiative, led by Jon Navarlaz, Managing Director of iAR, was awarded €25,364 to create a new communication system that will improve response times and agent coordination in patient management and transport in emergency situations.

Consultoría Informática Adhoc will start up MiCentro in collaboration with the SNS-O’s Support Service for Clinical Management and Healthcare Continuity in Primary Care Management. The project is coordinated by Sergio Chivite, the Service’s technical expert, and was awarded the amount of €22,740. David Santamaría from Consultoría Informática Adhoc will coordinate the proposal of creating a new SMS communication channel to improve management of doctor’s appointments, and the proposal of having healthcare centers send relevant information to their patients and users.

The company addressing the QuiroHelp challenge is TedCas Medical Systems, which was awarded €30,000 to implement the project. Jesús Miguel Pérez, the Director of TedCas, is leading the project and working with professionals from the CHN’s Service of General Surgery Ward B for the development of a chatbot service to improve the response times of scrub nurses in CHN operating rooms. Nurse Diana Marcilla is coordinating the healthcare team involved.

Finally, Desarrollos ANASINF was awarded €30,000 to develop the app UMD360, whose aim is to send gynecological cancer patients all the integrated and coordinated information and services designed by the Gynecological Cancer Multidisciplinary Unit. Ainhoa Castellano, the Director of Desarrollos ANASINF, is leading this innovative solution by working in coordination with Juan Carlos Muruzábal, Head of the CHN Obstetrics and Gynecology Service.

The inDemand Initiative

The European inDemand project is an initiative that receives funding from the Horizon 2020 program. Three pilot regions are participating: Murcia Region (Spain), Oulu Region (Finland) and Paris Region (France). The aim of the project is to check if the support model for demand-driven innovation in digital health is sustainable and applicable to other European regions called mirror regions and jointly known as the inDemand community. Navarre is participating as a mirror region and benefiting from the project’s methodology and success stories, but does not receive EU funding.