Artículos (Instituto de Biomedicina de Sevilla (IBIS))

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Editorial: Microglia in Neurodegenerative Diseases
(Frontiers Media SA, 2024) Li, Ting; Espinosa Oliva, Ana María; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Editorial: 15 years of Frontiers in Cellular Neuroscience: the dual role of microglia in (neuro)inflammation
(Frontiers Media, 2025) Herrera Carmona, Antonio José; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Age-dependent Progression from Clearance to Vulnerability in the Early Response of Periventricular Microglia to α-synuclein Toxic Species
(BioMed Central, 2025) Sirerol Piquer, Mª Salomé; Pérez Villalba, Ana; Duart Abadía, Pere; Belenguer, Germán; Gómez Pinedo, Ulises; Blasco Chamarro, Laura; Carrillo Barberà, Pau; Pérez Cañamás, Azucena; Navarro Garrido, Victoria; Dehay, Benjamin; Vitorica Ferrández, Francisco Javier; Fariñas, Isabel; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Ministerio de Ciencia e Innovación (MICIN). España
Cytoplasmic alpha-synuclein (αSyn) aggregates are a typical feature of Parkinson’s disease (PD). Extracellular insoluble αSyn can induce pathology in healthy neurons suggesting that PD neurodegeneration may spread through cell-to-cell transfer of αSyn proteopathic seeds. Early pro-homeostatic reaction of microglia to toxic forms of αSyn remains elusive, which is especially relevant considering the recently uncovered microglial molecular diversity. Here, we show that periventricular microglia of the subependymal neurogenic niche monitor the cerebrospinal fluid and can rapidly phagocytize and degrade different aggregated forms of αSyn delivered into the lateral ventricle. However, this clearing ability worsens with age, leading to an increase in microglia with aggregates in aged treated mice, an accumulation also observed in human PD samples. We also show that exposure of aged microglia to aggregated αSyn isolated from human PD samples results in the phosphorylation of the endogenous protein and the generation of αSyn seeds that can transmit the pathology to healthy neurons. Our data indicate that while microglial phagocytosis rapidly clears toxic αSyn, aged microglia can contribute to synucleinopathy spreading.
Correction: Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype
(PLOS, 2017-04) Huertas, Ismael; Jesús, Silvia; Lojo, José Antonio; García-Gómez, Francisco Javier; Cáceres-Redondo, María Teresa; Oropesa-Ruiz, Juan Manuel; Martín Rodríguez, Juan Francisco; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Psicología Experimental; Instituto de Biomedicina de Sevilla (IBIS); Instituto de Salud Carlos III; Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía. Consejería de Salud y Bienestar Social; Sociedad Andaluza de Neurología; Jacques and Gloria Gossweiler Foundation; Fundación Alicia Koplowitz; Fundación Mutua Madrileña; Programa "PFIS"; Programa Río Hortega; Programa Sara Borrell; Programa Miguel Servet
There are errors in the funding section.
Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype
(PLOS, 2017-03) Huertas, Ismael; Jesús, Silvia; Lojo, José Antonio; García-Gómez, Francisco Javier; Cáceres-Redondo, María Teresa; Oropesa-Ruiz, Juan Manuel; Martín Rodríguez, Juan Francisco; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Psicología Experimental; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía. Consejería de Salud y Bienestar Social; Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo; Fundación Alicia Koplowitz; Fundación Mutua Madrileña; Instituto de Salud Carlos III; Jacques and Gloria Gossweiler Foundation; Sociedad Andaluza de Neurología
Parkinson’s disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.
TMEM230 in Parkinson's disease in a southern Spanish population
(PLOS, 2018-05) Tejera-Parrado, Cristina; Jesús, Silvia; López-Ruíz, Adrián; Buiza Rueda, Dolores; Bonilla Toribio, Marta; Bernal Bernal, Inmaculada; Periñán Tocino, María Teresa; Vargas González, Laura; Gómez Garre, Pilar; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo; Junta de Andalucía. Consejería de Salud y Bienestar Social; Fundación Alicia Koplowitz; Fundación Mutua Madrileña; Jacques and Gloria Gossweiler Foundation; Sociedad Andaluza de Neurologia to Pablo Mir; Instituto de Salud Carlos III; Universidad de Sevilla
TMEM230 has been associated with autosomal dominant Parkinson’s disease (PD). Subsequent studies have remained negative, and none of previous described mutation has been reported anymore. We investigated the implication of this gene in the PD in a population of 703 PD patients and 695 unrelated healthy controls from southern Spain. Thirteen variants were found, twelve of them observed only in controls or in patients and controls, and one (c.190A>G) observed only in one patient. Subsequent analysis of this variant indicates that probably it is not pathogenic. In addition, we found a variation in the 3’-UTR (rs183551373) and related with the miRNA hsa-miR-4299 but it was observed only in healthy controls. Our results suggest that variants in TMEM230 gene are not associated with the development of PD.
Abnormal cerebellar connectivity and plasticity in isolated cervical dystonia
(PLOS, 2019-01) Porcacchia, Paolo; Álvarez de Toledo, Paloma; Rodríguez-Baena, Antonio; Martín Rodríguez, Juan Francisco; Palomar, Francisco J.; Vargas González, Laura; Jesús, Silvia; Koch, Giacomo; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. Departamento de Psicología Experimental; Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empresa; Junta de Andalucía. Consejería de Salud y Bienestar Social; Fundacion Alicia Koplowitz; Fundacion Mutua Madrilena; Instituto de Salud Carlos III; Jaques and Gloria Gossweiler Foundation; Ministerio de Economía y Competitividad (MINECO). España; Sociedad Andaluza de Neurología
There is increasing evidence that supports the role of the cerebellum in the pathophysiology of dystonia. We used transcranial magnetic stimulation to test the hypothesis that patients with cervical dystonia may have a disrupted cerebellar cortical connectivity at rest, and that cerebellar plasticity is altered too. We enrolled 12 patients with isolated cervical dystonia and 13 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right cerebellum and the left primary motor area. Changes in the amplitude of motor evoked potentials were analysed. Continuous and intermittent Theta Burst Stimulation over the cerebellum was also applied. The effects of these repetitive protocols on cortical excitability, on intra-cortical circuits and on cerebellar cortical inhibition were analysed. In healthy subjects, but not in dystonic patients, a conditioning stimulus over the cerebellum was able to inhibit the amplitude of the motor evoked potentials from primary motor cortex. In healthy subjects continuous and intermittent cerebellar Theta Burst Stimulation were able to decrease and increase respectively motor cortex excitability. Continuous Theta Burst Stimulation was able to abolish the cerebellar cortical inhibition observed in basal condition. These effects were not observed in patients with cervical dystonia. Cerebellar cortical connectivity and cerebellar plasticity is altered at rest in patients with cervical dystonia.
Imaging biomarkers of cortical neurodegeneration underlying cognitive impairment in Parkinson’s disease
(Springer Nature, 2025-01) Silva Rodríguez, Jesús; Labrador Espinosa, Miguel Ángel; Castro-Labrador, Sandra; Muñoz Delgado, Laura; Franco-Rosado, Pablo; Castellano Guerrero, Ana María; Carrillo García, Fátima María; Martín Rodríguez, Juan Francisco; Mir Rivera, Pablo; Grothe, Michel J.; Universidad de Sevilla. Departamento de Psicología Experimental; Universidad de Sevilla. Departamento de Medicina; Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo; Junta de Andalucía. Consejería de Salud y Familias; Universidad Carlos III de Madrid; Universidad de Sevilla; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Purpose: Imaging biomarkers bear great promise for improving the diagnosis and prognosis of cognitive impairment in Parkinson’s disease (PD). We compared the ability of three commonly used neuroimaging modalities to detect cortical changes in PD patients with mild cognitive impairment (PD-MCI) and dementia (PDD). Methods: 53 cognitively normal PD patients (PD-CN), 32 PD-MCI, and 35 PDD underwent concurrent structural MRI (sMRI), diffusion-weighted MRI (dMRI), and [18F]FDG PET. We extracted grey matter volumes (sMRI), mean diffusivity (MD, dMRI), and standardized uptake value ratios ([18F]FDG PET) for 52 cortical regions included in a neuroanatomical atlas. We assessed group differences using ANCOVA models and further applied a cross-validated machine learning approach to identify the modality-specific brain regions that are most indicative of dementia status and assessed their diagnostic accuracy for group separation using receiver operating characteristic analyses. Results: In sMRI, atrophy of temporal and posterior-parietal areas allowed separating PDD from PD-CN (AUC = 0.77 ± 0.07), but diagnostic accuracy was poor for separating PD-MCI from PD-CN (0.57 ± 0.10). dMRI showed most pronounced diffusivity changes in the medial temporal lobe, which provided excellent diagnostic performance for PDD (AUC = 0.87 ± 0.06), and a more modest but still significant performance for PD-MCI (AUC = 0.71 ± 0.09). Finally, [18F]FDG PET revealed pronounced hypometabolism in posterior-occipital regions, which provided the highest diagnostic accuracies for both PDD (AUC = 0.89 ± 0.05) and PD-MCI (AUC = 0.78 ± 0.05). In statistical comparisons, both [18F]FDG PET (p < 0.001) and dMRI (p < 0.031) outperformed sMRI for detecting PDD and PD-MCI. Conclusion: Among the tested modalities, [18F]FDG PET was most accurate for detecting cortical changes associated with cognitive impairment in PD, especially at early stages. Diffusion measurements may represent a promising MRI-based alternative.
Changes in Principal Caregiver Mood Affects the Mood of the Parkinson’s Disease Patient: The Vicious Cycle of Illness
(Sage Journals, 2023-03) Santos-García, Diego; de Deus Fonticoba, Teresa; Cores Bartolomé, Carlos; Feal Painceiras, María J.; Íñiguez-Alvarado, María Cristina; García Díaz, Iago; Jesús, Silvia; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Background: Although many studies have analyzed what factors contribute to caregiver burden in Parkinson’s disease (PD), there is currently no knowledge about how the status of the caregiver could impact the patient. Objective: The aim of this study was to analyze how the change in the caregiver’s status influences PD patients. Methods: PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers in Spain from the COPPADIS cohort were included in the study (V0). They were evaluated again at 2-year follow-up (V2). Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at V0 and V2. Multivariate models were used to analyze the impact of the change from V0 to V2 (Δ) on the caregiver’s status over the change in the patient’s status. Results: ΔBDI-II and ΔEUROHIS-QOL8 in the caregiver predicted ΔBDI-II (β = 0.32; p < 0.0001; R^2 = 0.71) and ΔEUROHIS-QOL8 (β = 0.39; p < 0.0001; R^2 = 0.68) in the patient, respectively. Variables related to the caregiver were not associated with changes in the patient´s health-related QoL (ΔPDQ-39 [39-item Parkinson’s disease Questionnaire]) or autonomy for activities of daily-living (ΔADLS [Schwab & England Activities of Daily Living Scale]). Conclusion: The change in the caregiver’s mood and global QoL was associated with the change in the patient’s mood and global QoL, respectively, independently of other variables of the disease influencing both patient´s aspects. Based on this finding, it could be of great importance to detect depression in the principal caregiver of a patient and act on it as earlier as possible.
Author Correction: Peripheral inflammatory immune response differs among sporadic and familial Parkinson’s disease (npj Parkinson's Disease, (2023), 9, 1, (12), 10.1038/s41531-023-00457-5)
(Springer Nature, 2023-02) Muñoz-Delgado, Laura; Macías-García, Daniel; Periñán Tocino, María Teresa; Jesús, Silvia; Adarmes-Gómez, Astrid D.; Bonilla Toribio, Marta; García Díaz, Sergio; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
In this article the affiliation details for Author Pablo Mir were incorrectly given as ‘Departamento de Medicina, Universidad de Sevilla, Seville, Spain’ but should have been ‘Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Seville, Spain’. The original article has been corrected.
Staging Parkinson's disease according to the MNCD (Motor/Non-motor/Cognition/Dependency) classification correlates with disease severity and quality of life
(Sage Journals, 2023-03) Santos-García, Diego; de Deus Fonticoba, Teresa; Cores Bartolomé, Carlos; Feal Painceiras, Maria J.; Íñiguez-Alvarado, Maria Cristina; García Díaz, Iago; Jesús, Silvia; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Results: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.
Prevalence and factors associated with drooling in Parkinson's disease: results from a longitudinal prospective cohort and comparison with a control group
(Wiley, 2023-01) Santos-García, Diego; de Deus Fonticoba, Teresa; Cores Bartolomé, Carlos; Feal Painceiras, María J.; Íñiguez-Alvarado, María Cristina; Jesús, Silvia; Buongiorno, Maria Teresa; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Economía y Competitividad (MINECO). España
Introduction: Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results: (e frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR . 1.032; p . 0.012), being male (OR . 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR. 1.020; p < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR. 1.012; p < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with >_2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR . 1.121; p . 0.007) as a predictor of drooling at V2. Conclusion: Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden. associated with a greater motor severity and NMS burden
Peripheral immune profile and neutrophil-to-lymphocyte ratio in progressive supranuclear palsy: Case–control study and meta-analysis
(Wiley, 2024-12) Muñoz-Delgado, Laura; Luque-Ambrosiani, A.; Zamora, B. B.; Macías-García, D.; Jesús, S.; Adarmes-Gómez, Astrid; Ojeda-Lepe, Elena; Carrillo García, Fátima María; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía. Consejeria de Economia, Innovacion, Ciencia y Empleo; Junta de Andalucía. Consejería de Salud y Bienestar Social; Junta de Andalucía. Consejería de Salud y Consumo; Junta de Andalucía. Consejería de Transformación Económica, Industria, Conocimiento y Universidades
Background and purpose: Peripheral inflammation is probably involved in the pathogenesis of progressive supranuclear palsy (PSP) and it may be a common feature with Parkinson's disease (PD). The peripheral immune profile in PSP remains unclear, as well as whether the inflammatory pathways differ from those in PD. The neutrophil-to-lymphocyte ratio (NLR) has been proven to be a well-established biomarker of systemic inflammation. This study aimed to evaluate the peripheral immune profile in PSP compared with PD. Methods: A cross-sectional study was conducted including patients with PSP and PD and healthy controls (HCs). Leukocyte subpopulations and the NLR were measured in peripheral blood. Multivariate linear regression and post hoc tests were applied. Electronic databases were searched in November 2023 to perform meta-analyses to clarify the peripheral immune profile in PSP. Results: Our cohort included 121 patients with PSP, 127 patients with PD and 266 HCs. The NLR was higher in PSP and PD compared with HCs. PSP had a higher neutrophil count compared with HCs. Whilst a lower lymphocyte count was found in PD compared with HCs, the lymphocyte count did not differ between PSP and HCs. The meta-analyses supported this immune profile. Conclusions: PSP and PD show an increased peripheral inflammation and a higher NLR compared with HCs. Different pathogenic inflammatory mechanisms are probably involved in PSP and PD, since in PSP this altered peripheral immune profile is mainly driven by neutrophils. Understanding the neutrophils' role in PSP may allow for the development of targeted therapies.
Dysphagia in Parkinson´s disease. A 5-year follow-up study
(Springer Nature, 2025-02) Santos-García, Diego; Deus Fonticoba, Teresa de; Jesús, Silvia; Cosgaya, Marina; García Caldentey, Juan; Caballol, Nuria; Legarda, Inés; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Economía y Competitividad (MINECO). España
Background and objective: Dysphagia at time of diagnosis suggests atypical parkinsonism instead Parkinson´s disease (PD). Our aim was to analyze the frequency of dysphagia in patients with early PD comparing with a control group and to identify related factors. Patients and methods Patients with early PD (≤ 2 years from symptoms onset) who were recruited from January/2016 to November/2017 (baseline visit; V0) and evaluated annually for 5 years from the Spanish cohort COPPADIS were included in this prospective study. Controls were assessed at baseline and at 2-, 4-, and 5-year follow-up. Dysphagia was defined as a score ≥ 1 in the item 20 of the Non-Motor Symptoms Scale (NMSS). Results: Dysphagia was more frequent at baseline in PD patients (19.6% [36/184]; 62.3 ± 8.3 years old; 56.8% males) than in controls (5.3% [11/206]; 60.9 ± 8.3 years old; 50% males) (p < 0.0001) and in all visits as well (p < 0.0001). A worse quality of sleep (Parkinson´s Disease Sleep Scale; OR = 0.974; p = 0.005), a greater impulse-control behavior (ICB) (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale; OR = 1.066; p = 0.014), and non-motor symptoms burden (Non-Motor Symptoms Scale; OR = 1.016; p = 0.021) were independent factors associated with dysphagia at baseline. In those subjects with dysphagia, no differences were observed between patients and controls in the mean NMSS-item 20 overtime, and it didn´t change throughout the follow-up. Conclusion: Dysphagia was frequent in early PD patients compared to controls. However, it was minor and did not progress over time. Sleep, ICB, and non-motor symptoms burden were related to dysphagia.
Dopamine agonist therapy in Parkinson's disease: Spanish expert consensus on its use in different clinical situations
(ScienceDirect, 2025-03) Santos García, D.; Pagonabarraga Mora, J.; Escamilla Sevilla, F.; García Ruiz, P. J.; Infante Ceberio, J.; Kulisevsky Bojarski, J.; Linazasoro Cristóbal, G.; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Background: Different types of therapies were proven effective for the medical management of motor and non-motor symptoms in Parkinson’s disease (PD). We aimed to gain consensus on the dopamine agonist (DA) therapy use in different clinical scenarios of Parkinson’s disease (PD) patients. Methods: This consensus study was based on the nominal group technique. Initially, a consensus group comprising 12 expert neurologists in the PD field identified the topics to be addressed and elaborated different evidence-based preliminary statements. Next, a panel of 48 Spanish neurologists expressed their opinion on an internet-based systematic voting program. Finally, initial ideas were reviewed and rewritten according to panel contribution and were ranked by the consensus group using a Likert-type scale. The analysis of data was carried out by using a combination of both qualitative and quantitative methods. The consensus was achieved if the statement reached ≥ 3.5 points in the voting process. Results: The consensus group produced 76 real-world recommendations. The topics addressed included 12 statements related to DA therapy in early PD, 20 statements concerning DA treatment strategy in patients with motor complications, 11 statements associated with DA drugs and their side effects, and 33 statements regarding DA therapy in specific clinical scenarios. The consensus group did not reach a consensus on 15 statements. Conclusion: The findings from this consensus method represent an exploratory step to help clinicians and patients in the appropriate use of DA in different stages and clinical situations of PD.
Understanding Parkinson disease in Spain: Genetic and clinical insights
(Wiley, 2025-01) Gómez Garre, Pilar; Martín Bornez, Miguel; Muñoz Delgado, Laura; Díaz-Belloso, Rafael; Periñán Tocino, María Teresa; Bonilla Toribio, Marta; García Díaz, Sergio; Carrillo García, Fátima María; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía. Consejería de Innovación, Ciencia y Empleo
Background and purpose: Parkinson disease (PD) is a complex and heterogeneous neurodegenerative disorder with a broad spectrum of clinical manifestations, determined by a complex interplay of environmental and genetic factors. This study aimed to investigate genetic variants associated with PD and assess their impact on the disease phenotype through genotype–phenotype correlations. Methods: We employed a targeted resequencing panel to analyze 27 genes linked to PD in a cohort of 1185 PD patients from southern Spain. Variants were categorized based on the American College of Medical Genetics and Genomics pathogenicity criteria. Demographic and clinical data were also collected. Results: Among the patients analyzed, 13.5% carried potential disease-causing pathogenic or likely pathogenic variants in 12 different genes, indicating significant genetic heterogeneity. The most frequently affected genes were LRRK2, PRKN, and GBA1 (accounting for 72.1% of positive cases). Sex-specific differences were observed, with a higher proportion of female patients carrying LRRK2 variants. Differences in age at onset and clinical features were also observed among the different mutated genes. Notably, variants in genes associated with atypical parkinsonism presented distinct clinical presentations, highlighting the importance of genetic factors in the differential diagnosis. Conclusions: Our study provides valuable information on the genetic landscape of PD and its clinical manifestations. The observed genotype–phenotype correlations, along with sex-specific differences, emphasize the complexity of PD pathogenesis, underlining the importance of personalized approaches to PD diagnosis and treatment. Further investigations into genetic interactions and population-specific effects are warranted to enhance our understanding of PD etiology and improve patient care.
Proteomic profiling of ewing sarcoma reveals a role for traf6 in proliferation and ribonucleoproteins/rna processing
(Omics Publishing Group, 2016) Madoz-Gúrpide, Juan; Herrero Martín, David; Gómez López, Gonzalo; Hontecillas Prieto, Lourdes; Biscuola, Michele; Chamizo, Cristina; García Domínguez, Daniel José; Marcilla, David; Amaral, Ana Teresa; Ordoñez, José Luis; Álava Casado, Enrique de; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Notwithstanding advances over the last decade in the comprehension of the molecular biology of Ewing sarcoma (ES), we still lack an understanding of critical issues, especially those regarding its genesis. In particular, little effort has been devoted to characterization of the proteic component of the mechanisms and pathways deployed by the activation of the fusion protein resulting from chromosomal translocation. We decided to investigate the proteic alterations of an ES cell line bearing a representative fusion protein. The combination of RNA interference of EWS FLI1 in the ES cell line TC-71, a proteomic analysis by 2-D electrophoresis and subsequent mass-spectrometry identification, and a global overrepresentation study detected changes in more than 500 spots. Forty-three proteins were identified as being significantly differentially abundant. As expected, we found and validated changes in proteins linked to nucleotide processing, transcription regulation, ribonucleoproteins, helicases, cell-cycle control and proliferation, and metabolic processes. Additionally, TNF receptor-associated factor 6 was revealed as a hub node. Our strategy showed the potential to reveal the protein interplay associated with the known functions of the fusion protein: binding to DNA and RNA in order to act as aberrant transcription factors or potent repressors, or by altering RNA processing.
Targeting IL-6 Trans-signalling by sgp130Fc Attenuates Severity in SARS-CoV-2 -Infected Mice and Reduces Endotheliopathy
(Elsevier, 2024) Rodríguez Hernández, María A.; Baena Bustos, Mercedes; Carneros, David; Zurita Palomo, Carola; Muñoz Pinillos, Pablo; Millán, Jaime; Padillo Ruiz, Francisco Javier; Smerdou, Cristian; von Kobbe, Cayetano; Rose John, Stefan; Bustos, Matilde; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Cirugía; Instituto de Salud Carlos III; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). España
Background: SARS-CoV-2 infection is considered as a relapsing inflammatory process with a dysregulation of IL-6 signalling. Classic IL-6 signalling is thought to represent a defence mechanism against pathogens. In contrast, IL-6 trans-signalling has pro-inflammatory effects. In severe COVID-19, therapeutic strategies have focused on global inhibition of IL-6, with controversial results. We hypothesized that specific blockade of IL-6 trans-signalling could inhibit inflammatory response preserving the host defence activity inherent to IL-6 classic signalling. Methods: To test the role of the specific IL-6 trans-signalling inhibition by sgp130Fc in short- and long-term consequences of COVID-19, we used the established K18-hACE2 transgenic mouse model. Histological as well as immunohistochemical analysis, and pro-inflammatory marker profiling were performed. To investigate IL-6 trans-signalling in human cells we used primary lung microvascular endothelial cells and fibroblasts in the presence/absence of sgp130Fc. Findings: We report that targeting IL-6 trans-signalling by sgp130Fc attenuated SARS-CoV-2-related clinical symptoms and mortality. In surviving mice, the treatment caused a significant decrease in lung damage. In vitro, IL-6 trans-signalling induced strong and persisting JAK1/STAT3 activation in endothelial cells and lung fibroblasts with proinflammatory effects, which were attenuated by sgp130Fc. Our data also suggest that in those cells with scant amounts of IL-6R, the induction of gp130 and IL-6 by IL-6:sIL-6R complex sustains IL-6 trans-signalling. Interpretation: IL-6 trans-signalling fosters progression of COVID-19, and suggests that specific blockade of this signalling mode could offer a promising alternative to mitigate both short- and long-term consequences without affecting the beneficial effects of IL-6 classic signalling. These results have implications for the development of new therapies of lung injury and endotheliopathy in COVID-19.
Impact of school-based health promotion interventions aimed at different behavioral domains: a systematic review
(ScienceDirect, 2014-10) Lima Serrano, Marta; Lima Rodríguez, Joaquín Salvador; Universidad de Sevilla. Departamento de Enfermería; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS969: Innovación en Cuidados y Determinantes Sociales en Salud
Objective: Given that lifestyleshave similar determinants and that school-based interventions are usually targeted at all the risks that affect adolescents, the objective of this systematic review was to summarize the characteristics and effects of school-based interventions acting on different behavioral domains of adolescent health promotion. Methods: The review process was conducted by two independent reviewers who searched PubMed, Scopus, PsycINFO, and ERIC databases for experimental or observational studies with at least two measures of results published from 2007 to 2011, given that the research information available doubles every 5 years. Methodological quality was assessed with a standardized tool. Results: Information was extracted from 35 studies aiming to prevent risk behaviors and promote healthy nutrition, physical activity, and mental and holistic health. Activities were based on theoretical models and were classified into interactive lessons, peer mediation, environmental changes, parents’ and community activities, and tailored messages by computer-assisted training or other resources, usually including multiple components. In some cases, we identified some moderate to large, short- and long-term effects on behavioral and intermediate variable. Conclusions: This exhaustive review found that well-implemented interventions can promote adolescent health. These findings are consistent with recent reviews. Implications for practice, public health, and research are discussed.
Enfermería Comunitaria y salud digital en tiempos de la COVID-19
(Asociación de Enfermería Comunitaria, 2021-05) Lima Serrano, Marta; Carrión Robles, Trinidad; Herráiz Mallebrera, Antonia; Arrabal Téllez, Ana Belén; Universidad de Sevilla. Departamento de Enfermería; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS969: Innovación en Cuidados y Determinantes Sociales en Salud
Objetivo: actualizar y ampliar conocimientos de salud digital en el ámbito de la Enfermería Comunitaria y la Atención Primaria de Salud durante la pandemia de la COVID-19. Método: revisión narrativa. Descripción de las competencias y herramientas de salud digital más utilizadas en la pandemia y de estudios relacionados con su uso en Atención Primaria de Salud por las enfermeras comunitarias; incluyendo el análisis de la experiencia llevada a cabo por las enfermeras del Centro de Salud de Nerja (Málaga). Resultados: organizaciones internacionales de la salud y otras fuentes aportan valiosa bibliografía sobre el potencial de las herramientas digitales, bajo el marco de la pandemia por COVID-19, recomendando su utilización a las enfermeras en la aplicación del cuidado. Los estudios consultados muestran la utilidad de la salud digital para la enfermera comunitaria en el mantenimiento de la atención domiciliaria a las personas en situación de aislamiento, así como el análisis de la experiencia llevada a cabo por las enfermeras. Conclusiones: la salud digital representa un escenario ideal en situaciones de aislamiento, como el producido por una pandemia, en este caso por el virus SARS CoV-2, y las enfermeras obsevan que es un buen recurso en situaciones de aislamiento, al tiempo que se muestra capacidad de adaptación a los cambios estructurales que la pandemia por COVID-19 exige. Ante el colapso vivido en Atención Primaria, las intervenciones de salud digital podrían facilitar los cuidados enfermeros por medios virtuales siempre que se acelere la innovación digital en el Sistema Nacional de Salud. El impacto de la COVID-19 exige, como enfermeras comunitarias implicación en la transformación hacia la salud digital.

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