Spatial pattern of biotic and abiotic variables involved in root rot mortality in Quercus ilex L. subsp. ballota (Desf.) Samp. in south-western Iberian Peninsula

Desde la última mitad del siglo XX, los bosques de Quercus y dehesas del sur de la Península Ibérica vienen experimentando un progresivo deterioro forestal de sus masas arbóreas, denominado, de forma genérica, como decaimiento o seca de los Quercus. Este declive está motivado por multitud de factores bióticos y abióticos que actúan de forma independiente o como combinación de ellos, y entre los que destacan las perturbaciones motivadas por el cambio climático global, la falta de regeneración natural de los bosques, la escasez de silvicultura y de gestión agroganadera, así como la intensificación, cada vez mayor, del tránsito de material vegetal a nivel mundial, sin el suficiente control fitosanitario en los viveros que impida la invasión y la dispersión de plagas y enfermedades forestales. En este síndrome complejo, se ha identificado la acción primaria del oomiceto patógeno invasor no nativo de podredumbre radical, Phytophthora cinnamomi Rands., el cual provoca la muerte de raíces finas, generando síntomas de estrés hídrico que se presentan en forma de puntisecado regresivo de ramas y defoliación de la copa del árbol y, en ocasiones, la muerte del individuo. Con esta Tesis Doctoral se pretende aumentar el conocimiento sobre la relación entre las características estructurales del arbolado y los factores abióticos (estructura física y química del suelo, topografía del paisaje y climatología) con la distribución espaciotemporal de oomicetos patógenos de podredumbre radical (Phytophthora spp. y Pythium spp.) en especies del género Quercus spp. A partir de estas relaciones, se ha estudiado cómo influyen sobre el estado de salud del arbolado (defoliación de las copas y mortalidad) la triple interacción patógeno-huésped-ambiente a diferentes escalas territoriales (árbol, rodal y región), y en diferentes tipos de formaciones vegetales, como son las repoblaciones forestales sobre tierras agrarias y las dehesas de Quercus, en Andalucía. Para llevar a cabo esta investigación, el trabajo se estructuró en 7 capítulos que se describen a continuación. El Capítulo 1, enmarca los antecedentes teóricos que sustentan la justificación de esta Tesis Doctoral y plantea los objetivos generales y específicos de la misma. El Capítulo 2, aborda la importancia que tiene, en un momento puntual, la heterogeneidad de las propiedades fisicoquímicas del suelo, la humedad del suelo y la influencia de la cobertura del dosel de una repoblación forestal de Quercus ilex, a nivel de árbol individual, sobre la distribución espacial en suelo, a pequeña escala, de las unidades formadoras de colonias (ufc) de Phytophthora cinnamomi. Para ello se utilizaron Modelos Lineales Mixtos Generalizados e índices de agregación y agrupación de variables mediante la herramienta SADIE. Los resultados indicaron que las variables limo, materia orgánica, P, K y humedad del suelo, principalmente, influyeron sobre la distribución de ufc. La variabilidad de las condiciones de los micrositios, pueden predecir qué áreas alrededor de los árboles influyen en la mayor o menor disponibilidad de estos oomicetos en el suelo. El Capítulo 3, muestra los patrones de distribución espacial, a escala de parcela, de las ufc del oomiceto Phytophthora cinnamomi en la rizosfera de plantaciones de Q. ilex y Q. suber, influenciados por la disposición de las propiedades fisicoquímicas, la humedad del suelo y las propiedades topográficas de la repoblación. Las implicaciones derivadas de las interacciones entre dichos factores bióticos y abióticos se observaron a través de los parámetros de defoliación y mortalidad del arbolado tras un periodo de 8 años, usando modelos de ecuaciones estructurales e índices de agregación y agrupación de variables mediante la herramienta SADIE. Los resultados muestran la mayor susceptibilidad de la encina frente al alcornoque en presencia del patógeno, con porcentajes de defoliación y mortalidad más elevados para la primera especie. A su vez los daños se correlacionaron con la textura y los nutrientes del suelo. En la defoliación de Q. ilex, influyó principalmente las propiedades químicas del suelo, mientras que para Q. suber, también influyó la topografía y la humedad del suelo. La mayor presencia de oomicetos se localizó en zonas de mayor humedad edáfica, menores pendientes, orientación norte y baja radiación solar. El Capítulo 4, analiza el efecto de los factores bióticos, abióticos (edáficos, topográficos y ambientales) sobre el decaimiento forestal de los Quercus y sobre la propagación de oomicetos patógenos invasores no nativos de podredumbre radical (género Phytophthora spp.) a escala regional de Andalucía. Se estudia la dinámica espaciotemporal de la defoliación y la mortalidad del arbolado registrada en la Red Regional de parcelas de Seguimiento de Daños de Andalucía (Red SEDA, ICP Nivel I, 2000-2016) en relación con la presencia de oomicetos y los valores medios y anuales ambientales. Se usaron varios enfoques estadísticos (curvas de supervivencia de Kaplan-Meier, gráficos de estimación de densidad Kernel y Modelos Lineales Mixtos Generalizados) para analizar 3635 árboles (152 parcelas). La defoliación y la mortalidad anuales se correlacionaron con la temperatura media anual, el Índice de Precipitación Evapotranspiración Estandarizada (SPEI18verano y SPEI1primavera), el contenido de materia orgánica del suelo y la precipitación anual, adquiriendo mayor relevancia la acción del patógeno en estas condiciones ambientales. Las redes regionales de sanidad forestal se muestran como herramienta crucial en las estrategias de gestión forestal adaptativa frente al cambio climático. El Capítulo 5, evalúa y cartografía sobre una forestación de Q. ilex y Q. suber, los daños asociados al efecto de patógenos no nativos de podredumbre radical (Phytophthora spp.), a escala de árbol individual, utilizando técnicas LiDAR de alta densidad e imágenes multiespectrales de alta resolución. Para ello se utilizó el nivel de defoliación de 429 árboles que, mediante procesado de segmentación de copas, permitió obtener las métricas LiDAR e índices de vegetación basados en sus bandas espectrales. Ello dio lugar a la estimación de la defoliación mediante un modelo no paramétrico que permitió generar el mapa de daños de la plantación. El Capítulo 6, aúna los conocimientos y resultados obtenidos en esta Tesis en forma de discusión general, aportando un enfoque global de los hitos más relevantes alcanzados a lo largo del estudio. Asimismo, se incluyen las limitaciones presentadas durante los trabajos y se expone el enfoque de las nuevas líneas de investigación que se derivan de esta Tesis. El Capítulo 7, presenta las conclusiones generales de la Tesis, sintetizadas a continuación. Los patrones de distribución espacial de las ufc del patógeno de podredumbre radical, P. cinnamomi, en dehesas de Quercus y repoblaciones de Q. ilex y Q. suber, implicados en la dinámica temporal de los procesos de defoliación y de mortalidad de estas especies arbóreas, están influenciados por la variabilidad de factores bióticos y abióticos del medio, como son las propiedades fisicoquímicas del suelo, la cobertura del dosel arbóreo, la presencia y estado fitosanitario de los huéspedes y su sistema radical, los cambios climatológicos, así como la heterogeneidad topográfica del paisaje. El análisis espacial a diferentes escalas de árbol, rodal y región puede servir como herramienta de predicción de áreas más susceptibles de albergar a estos oomicetos y, por tanto, como medio para aplicar estrategias de gestión forestal adaptativa frente al decaimiento de estos ecosistemas.Since the last half of the 20th century, Quercus forests and dehesas in the south of the Iberian Peninsula have been experiencing a progressive forest deterioration of their tree stands, generically known as Quercus decline or seca Quercus. This decline is caused by a multitude of biotic and abiotic factors acting independently or in combination, including disturbances caused by global climate change, the lack of natural regeneration of forests, the scarcity of forestry and agro-livestock management, as well as the increasing intensification of the transit of plant material worldwide, without sufficient phytosanitary control in nurseries to prevent the invasion and spread of forest pests and diseases. In this complex syndrome, the primary action of the nonnative invasive root rot pathogenic oomycete, Phytophthora cinnamomi Rands., has been identified, which causes the death of fine roots, generating symptoms of water stress in the form of regressive top-drying of branches and defoliation of the tree crown and, sometimes, death of the tree. This PhD thesis aims to increase knowledge of the relationship between the structural characteristics of trees and abiotic factors (physical and chemical soil structure, landscape topography and climatology) with the spatiotemporal distribution of pathogenic root rot oomycetes (Phytophthora spp. and Pythium spp.) in species of the genus Quercus spp. Based on these relationships, we studied the influence of the triple interaction pathogen-host-environment on tree health (crown defoliation and mortality) at different territorial scales (tree, stand and region), and in different types of plant formations afforestation on agricultural land and Quercus dehesas in Andalusia. To carry out this research, the work was structured in 7 chapters which are described below. Chapter 1, frames the theoretical background that supports this doctoral Thesis’s justification and sets out its general and specific objectives. Chapter 2, addresses the importance of the heterogeneity of soil physicochemical properties, soil moisture and the influence of the canopy cover of a Quercus ilex afforestation, at individual tree level, on the small-scale spatial distribution of colony forming units (cfu) of Phytophthora cinnamomi in the soil. Generalised Linear Mixed Models and variable aggregation and clustering indices were used using the SADIE tool. The results indicated that silt, organic matter, P, K and soil moisture variables mainly influenced the distribution of cfu. The variability of microsite conditions can predict which areas around the trees influence the greater or lesser availability of these oomycetes in the soil. Chapter 3, shows the spatial distribution patterns, at plot scale, of cfu of the oomycete Phytophthora cinnamomi in the rhizosphere of Q. ilex and Q. suber plantations, influenced by the arrangement of physico-chemical properties, soil moisture and topographical properties of the stand. The implications derived from the interactions between these biotic and abiotic factors were observed through defoliation and tree mortality parameters after eight years, using structural equation models and aggregation and grouping indices of variables using the SADIE tool. The results show the greater susceptibility of holm oak versus cork oak in the presence of the pathogen, with higher percentages of defoliation and mortality for the former species. Damage was correlated with soil texture and nutrients. Defoliation of Q. ilex was mainly influenced by soil chemical properties, while for Q. suber, topography and soil moisture were also influential. The highest presence of oomycetes was located in areas with higher soil moisture, lower slopes, northern orientation and low solar radiation. Chapter 4, analyses the effect of biotic, abiotic (edaphic, topographic and environmental) factors on Quercus forest decline and the spread of nonnative invasive pathogenic root rot oomycetes (genus Phytophthora spp.) at a regional scale in Andalusia. The spatiotemporal dynamics of tree defoliation and mortality recorded in the Regional Network of Damage Monitoring Plots of Andalusia (SEDA Network, ICP Level I, 2000-2016) are studied in relation to the presence of oomycetes and mean and annual environmental values. Several statistical approaches (Kaplan-Meier survival curves, Kernel density estimation plots and Generalised Linear Mixed Models) were used to analyse 3635 trees (152 plots). Annual defoliation and mortality were correlated with mean annual temperature, Standardised Precipitation Evapotranspiration Index (SPEI18summer and SPEI1spring), soil organic matter content and annual precipitation, with pathogen action becoming more relevant under these environmental conditions. Regional forest health networks are shown to be a crucial tool in adaptive forest management strategies in the face of climate change. Chapter 5, assesses and maps damage associated with the effect of nonnative root rot pathogens (Phytophthora spp.) on a Q. ilex and Q. suber afforestation at the individual tree scale, using high-density LiDAR techniques and high-resolution multispectral imagery. The defoliation level of 429 trees was used to obtain LiDAR metrics and vegetation indices based on their spectral bands by means of crown segmentation processing. This resulted in the estimation of defoliation using a non-parametric model that allowed the generation of the damage map of the plantation. Chapter 6, brings together the knowledge and results obtained in this Thesis in a general discussion, providing a global approach to the most relevant milestones reached throughout the study. It also includes the limitations presented during the work and sets out the focus of the new lines of research arising from this Thesis. Chapter 7, presents the general conclusions of the Thesis, which are synthesised below. The spatial distribution patterns of the cfu of the root rot pathogen, P. cinnamomi, in Quercus dehesas and afforestations of Q. ilex and Q. suber, involved in the temporal dynamics of defoliation and mortality processes of these tree species, are influenced by the variability of biotic and abiotic environmental factors, such as soil physicochemical properties, tree canopy cover, the presence and phytosanitary status of the hosts and their root system, climatological changes, as well as the topographic heterogeneity of the landscape. Spatial analysis at different tree, stand and regional scales can serve as tool for predicting areas more susceptible to host these oomycetes and, therefore, to apply adaptive forest management strategies against the decline of these ecosystems

CD69 expression on regulatory T cells protects from immune damage after myocardial infarction.

Increasing evidences advocate for an important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed a significant CD69 overexpression on Treg cells after MI. Our results in mice showed that CD69 expression on Treg cells increased survival after left-anterior-descending coronary artery (LAD)-ligation. Cd69-/- mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Treg cells, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Treg cells to Cd69-/- mice after LAD-ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from two independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of re-hospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Treg cells as a potential prognostic factor and a therapeutic option to prevent HF after MI.This study was supported by competitive grants from the Ministerio de Ciencia e Innovación (MCIN), through the Carlos III Institute of Health (ISCIII)-Fondo de Investigación Sanitaria (PI22/01759) to P.M.; RTI2018-094727-B-100 to J. M-G; Comunidad de Madrid grants S2017/BMD-3671-INFLAMUNE-CM to P.M. and FSM.; Fundació La Marató TV3 (20152330 31) to J.M-G and F.S-M.; Ministerio de Ciencia e Innovación (MCIN) RTI2018-099357-B-I00, and CIBERFES (CB16/10/00282), Human Frontier Science Program (grant RGP0016/2018), and Leducq Transatlantic Networks (17CVD04) to JAE. AC is supported by Marie Skłodowska- Curie grant (agreement No. 713673). R.B-D. is supported by Formación de Profesorado Universitario (FPU16/02780) program from the Spanish Ministry of Education, Culture and Sports. The CNIC is supported by the ISCIII, the MCIN and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Artificial intelligence within the interplay between natural and artificial computation:Advances in data science, trends and applications

Artificial intelligence and all its supporting tools, e.g. machine and deep learning in computational intelligence-based systems, are rebuilding our society (economy, education, life-style, etc.) and promising a new era for the social welfare state. In this paper we summarize recent advances in data science and artificial intelligence within the interplay between natural and artificial computation. A review of recent works published in the latter field and the state the art are summarized in a comprehensive and self-contained way to provide a baseline framework for the international community in artificial intelligence. Moreover, this paper aims to provide a complete analysis and some relevant discussions of the current trends and insights within several theoretical and application fields covered in the essay, from theoretical models in artificial intelligence and machine learning to the most prospective applications in robotics, neuroscience, brain computer interfaces, medicine and society, in general.BMS - Pfizer(U01 AG024904). Spanish Ministry of Science, projects: TIN2017-85827-P, RTI2018-098913-B-I00, PSI2015-65848-R, PGC2018-098813-B-C31, PGC2018-098813-B-C32, RTI2018-101114-B-I, TIN2017-90135-R, RTI2018-098743-B-I00 and RTI2018-094645-B-I00; the FPU program (FPU15/06512, FPU17/04154) and Juan de la Cierva (FJCI-2017–33022). Autonomous Government of Andalusia (Spain) projects: UMA18-FEDERJA-084. Consellería de Cultura, Educación e Ordenación Universitaria of Galicia: ED431C2017/12, accreditation 2016–2019, ED431G/08, ED431C2018/29, Comunidad de Madrid, Y2018/EMT-5062 and grant ED431F2018/02. PPMI – a public – private partnership – is funded by The Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbott, Biogen Idec, F. Hoffman-La Roche Ltd., GE Healthcare, Genentech and Pfizer Inc

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.Depto. de MedicinaFac. de MedicinaTRUEFundación Madrileña de Hematología y HemoterapiaFundación Leucemia y LinfomaAsociación Madrileña de Hematología y Hemoterapiapu

Epigenetic clocks in relapse after a first episode of schizophrenia

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: differences between males and females

BackgroundDeficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset.Materials and methodsThe initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up.ResultsFEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = −0.307, p = 0.012) were significantly associated with functioning.ConclusionOur data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended

CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative

13 páginas,1 figura, 3 tablas, 1 apéndice. Se extraen los autores pertenecientes a The CIBERER network que trabajan en Centros del CSIC del Appendix ACIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research.This study has been funded by Instituto de Salud Carlos III (ISCIII) and Spanish Ministry of Science and InnovationPeer reviewe

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Angiographic demonstration of neoangiogenesis after intra-arterial infusion of autologous bone marrow mononuclear cells in diabetic patients with critical limb Ischemia

Licencia Creative Commons Reconocimiento-No comercial.Critical limb ischemia in diabetic patients is associated with high rates of morbidity and mortality. Subopti-mal responses to the available medical and surgical treatments are common in these patients, who also demonstrate limited vascular homeostasis. Neovasculogenesis induced by stem cell therapy could be a useful approach for these patients. Neovasculogenesis and clinical improvement were compared at baseline and at 3 and 12 months after autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in diabetic patients with peripheral artery disease. We conducted a prospective study to evaluate the safety and efficacy of intra-arterial administration of autologous BMMNCs (100-400 × 10 6 cells) in 20 diabetic patients with severe below-the-knee arterial ischemia. Although the time course of clinical effects differed among patients, after 12 months of follow-up all patients presented a notable improvement in the Rutherford-Becker classification, the University of Texas diabetic wound scales, and the Ankle-Brachial Index in the target limb. The clinical outcome was consistent with neovasculogenesis, which was assessed at 3 months by digital subtraction angiography and quantified by MetaMorph software. Unfortunately, local cell therapy in the target limb had no beneficial effect on the high mortality rate in these patients. In diabetic patients with critical limb ischemia, intra-arterial perfusion of BMMNCs is a safe procedure that generates a significant increase in the vascular network in ischemic areas and promotes remarkable clinical improvement.The authors are supported by the Fundación Progreso y Salud, Consejería de Salud, Junta de Andalucía (Grant PI-0022/2008), the Ministry of Science and Innovation (Red TERCEL Grant RD06/0010/0025; Instituto de Salud Carlos III Grant PI10/00964), and the Ministry of Health and Consumer Affairs (Advanced Therapies Program Grant TRA-120). CIBERDEM is an initiative of the Instituto de Salud Carlos III.Peer Reviewe