Artículos (Instituto de Biomedicina de Sevilla (IBIS))

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  • Acceso AbiertoArtículo
    Delayed changes in the transcriptomic profile of cerebral arteries in a rat model of subarachnoid hemorrhage
    (Elsevier, 2025-02) Revilla González, Gonzalo; González Montelongo, María Del Carmen; Vasconcelos, Elton; Ureña López, Juan; Shi, Jian; Castellano Orozco, Antonio Gonzalo; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica
    Aneurismal subarachnoid hemorrhage (aSAH) is a neurovascular disease characterized by blood released into the subarachnoid space due to rupture of the cerebral arteries. After the onset of bleeding, secondary associated vasospasm (VSP) remains a dramatic side effect that causes severe comorbidities. We analyzed alterations in the expression profiles of arteries from a rat model of SAH using microarray and bioinformatics approaches. A single injection autologous blood rat model, previously characterized in our laboratory, was used. We performed a total RNA extraction and a microarray analysis of cerebral arteries from animals 7 days after surgery to study the delayed transcriptional changes induced by SAH. To assess the functional relationship between differently expressed genes, we run a combination of gene enrichment tools: GSEA, ClueGO, and ClusterProfiler. Our results showed that in SAH animals, the gene sets related to inflammation and immune system activation were up-regulated; genes related to the pathways involved in the regulation of muscle contraction had their expression disturbed; and the gene categories associated with DNA damage and repair were overrepresented. In conclusion, our results suggest that, after the SAH insult, multiple mechanisms, rather than a single cause, are activated at the same time in the cerebral vessels to trigger vascular alterations.
  • Acceso AbiertoArtículo
    Nueva variante KCNQ1 c.604 + 1G >C asociada con síndrome de Jervell-Lange Nielsen en homocigosis y heterocigosis compuesta
    (Ediciones Doyma S A, 2022-06) Arana Rueda, Eduardo; Rosa Pezzotti, Maria; Pedrote, Alonso; Marcos Fuentes, Laura; Frutos-López, Manuel; Castellano Orozco, Antonio Gonzalo; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía; Universidad de Sevilla. CTS591: Fisiopatología molecular del sistema cardiovascular.
    El síndrome de QT largo (SQTL) congénito es una enfermedad hereditaria caracterizada por una alteración de la repolarización cardiaca (prolongación intervalo QT) y susceptibilidad a la muerte súbita debida a torsade de pointes. La forma más grave de presentación, el síndrome de Jervell y Lange-Nielsen (SJLN), se asocia con sordera neurosensorial y se debe a variantes en homocigosis o heterocigosis compuesta de 2 posibles genes (KCNQ1 y KCNE1) y tiene una prevalencia muy baja, 1-4 millones de niños (menos del 1% de los pacientes con SQTL), y los casos descritos en nuestro medio son anecdóticos1. Se presentan los casos de 2 familias con SJLN debido a una misma variante no descrita previamente (KCNQ1 c.604 + 1G >C) presentada en homocigosis en un caso y en heterocigosis compuesta en el otro, con un análisis molecular de los cambios provocados por esta variante.
  • Acceso AbiertoArtículo
    Changes in arterial myocyte excitability induced by subarachnoid hemorrhage in a rat model
    (Elsevier Science Inc, 2024-06) Revilla Gonzalez, Gonzalo; Ureña López, Juan; González-Montelongo, María del Carmen; Castellano Orozco, Antonio Gonzalo; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Instituto de Biomedicina de Sevilla (IBIS); Gobierno de España; Junta de Andalucía; Universidad de Sevilla. CTS591: Fisiopatología molecular del sistema cardiovascular.
    Aneurismal subarachnoid hemorrhage (aSAH) is a neurovascular disease produced by the rupture of the cerebral arteries and the extravasation of blood to the subarachnoid space and is accompanied by severe comorbidities. Secondarily associated vasospasm is one of the main side effects after hydrocephalus and possible rebleeding. Here, we analyze the alterations in function in the arteries of a rat model of SAH. For this, autologous blood was injected into the cisterna magna. We performed electrophysiological, micro fluorimetric, and molecular biology experiments at different times after SAH to determine the functional and molecular changes induced by the hemorrhage. Our results confirmed that in SAH animals, arterial myocytes were depolarized on days 5 and 7, had higher [Ca2+]i on baseline, peaks and plateaus, and were more excitable at low levels of depolarization on day 7, than in the control and sham animals. Microarray analysis showed that, on day 7, the sets of genes related to voltage-dependent Ca2+ channels and K+dynamics in SAH animals decreased, while the voltage-independent Ca2+dynamics genes were over-represented. In conclusion, after SAH, several mechanisms involved in arterial reactivity were altered in our animal model, suggesting that there is no unique cause of vasospasm and alterations in several signaling pathways are involved in its development.
  • Acceso AbiertoArtículo
    HDL anti-inflammatory function is impaired and associated with high SAA1 and low APOA4 levels in aneurysmal subarachnoid hemorrhage
    (Sage, 2023) Azúa-López, Zaida Ruiz de; Pezzotti, M Rosa; González-Díaz, Ángela; Meilhac, Olivier; Ureña, Juan; Amaya-Villar, Rosario; Castellano Orozco, Antonio Gonzalo; Varela Pérez, Lourdes María; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS591: Fisiopatología molecular del sistema cardiovascular.
    Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease with high morbidity and mortality rates. Within 24 hours after aSAH, monocytes are recruited and enter the subarachnoid space, where they mature into macrophages, increasing the inflammatory response and contributing, along with other factors, to delayed neurological dysfunction and poor outcomes. High-density lipoproteins (HDL) are lipid-protein complexes that exert anti-inflammatory effects but under pathological conditions undergo structural alterations that have been associated with loss of functionality. Plasma HDL were isolated from patients with aSAH and analyzed for their anti-inflammatory activity and protein composition. HDLisolated from patients lost the ability to prevent VCAM-1 expression in endothelial cells (HUVEC) and subsequent adhesion of THP-1 monocytes to the endothelium. Proteomic analysis showed that HDL particles from patients had an altered composition compared to those of healthy subjects. We confirmed by western blot that low levels of apolipo protein A4 (APOA4) and high of serum amyloid A1 (SAA1) in HDL were associated with the lack of anti-inflammatory function observed in aSAH. Our results indicate that the study of HDL in the pathophysiology of aSAH is needed, and functional HDL supplementation could be considered a novel therapeutic approach to the treatment of the inflamma tory response after aSAH.
  • Acceso AbiertoArtículo
    Dual cholinergic signals regulate daily migration of hematopoietic stem cells and leukocytes
    (Elsevier, 2019-01) García-García, Andrés; Korn, Claudia; García-Fernández, María; Domingues, Olivia; Villadiego Luque, Francisco Javier; Martín-Pérez, Daniel; Pérez Simón, José Antonio; Toledo Aral, Juan José; Méndez-Ferrer, Simón; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Instituto de Biomedicina de Sevilla (IBIS); Gobierno de España
    Hematopoietic stem and progenitor cells (HSPCs) and leukocytes circulate between the bone marrow (BM) and peripheral blood following circadian oscillations. Autonomic sympathetic noradrenergic signals have been shown to regulate HSPC and leukocyte trafficking, but the role of the cholinergic branch has remained unexplored. We have investigated the role of the cholinergic nervous system in the regulation of day/night traffic of HSPCs and leukocytes in mice. We show here that the autonomic cholinergic nervous system (including parasympathetic and sympathetic) dually regulates daily migration of SPC sand leukocytes.At night, central parasympathetic cholinergic signals dampen sympathetic noradrenergic tone and decrease BM egress of HSPCs and leukocytes. However, during the daytime, derepressed sympathetic noradrenergic activity causes predominant B Megressof HSPC sand leukocytes viab3–adre ergic receptor.This egress is locally supported by light-triggered sympathetic cholinergic activity, which inhibits BM vascular cellad hesionand homing. Insummary,central(parasympathetic)and local (sympathetic) cholinergic signals regulate day/night oscillations of circulating HSPCs and leukocytes. This study shows how both branches of the autonomic nervous system cooperate to orchestrate daily traffic of HSPCs and leukocytes.
  • Acceso AbiertoArtículo
    Extracellular matrix protein anosmin‑1 overexpression alters dopaminergic phenotype in the CNS and the PNS with no pathogenic consequences in a MPTP model of Parkinson’s disease
    (Springer, 2023-03-30) Villadiego Luque, Francisco Javier; García Swinburn, Roberto; García González, Diego; Lebrón-Galán, Rafael; Murcia-Belmonte, Verónica; García Roldán, Ernesto; Suárez-Luna, Nela; Nombela, Cristina; Marchena, Miguel Ángel; Castro, Fernando de; Toledo Aral, Juan José; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Instituto de Biomedicina de Sevilla (IBIS); Gobierno de España; Instituto de Salud Carlos III; Junta de Andalucía; Universidad de Sevilla. CTS517: Fisiología molecular.
    The development and survival of dopaminergic neurons are influenced by the fibroblast growth factor (FGF) pathway. Anosmin-1 (A1) is an extracellular matrix protein that acts as a major regulator of this signaling pathway, controlling FGF diffusion, and receptor interaction and shuttling. In particular, previous work showed that A1 overexpression results in more dopaminergic neurons in the olfactory bulb. Prompted by those intriguing results, in this study, we investigated the effects of A1 overexpression on different populations of catecholaminergic neurons in the central (CNS) and the peripheral nerv ous systems (PNS). We found that A1 overexpression increases the number of dopaminergic substantia nigra pars compacta (SNpc) neurons and alters the striosome/matrix organization of the striatum. Interestingly, these numerical and morphological changes in the nigrostriatal pathway of A1-mice did not confer an altered susceptibility to experimental MPTP-parkinsonism with respect to wild-type controls. Moreover, the study of the effects of A1 overexpression was extended to different dopa minergic tissues associated with the PNS, detecting a significant reduction in the number of dopaminergic chemosensitive carotid body glomus cells in A1-mice. Overall, our work shows that A1 regulates the development and survival of dopamin ergic neurons in different nuclei of the mammalian nervous system.
  • Acceso AbiertoArtículo
    Rheological and mechanical properties of hydrophilic dispersions using a new hydrophobically modified polymer and Igepal (R) CO520
    (Elsevier, 2011-08-15) Lucero Muñoz, María Jesús; Claro Cala, Carmen María; Casas Delgado, Marta; Jiménez Castellanos, María Rosa; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS-1015: Desarrollo galénico de medicamentos y productos cosméticos; Universidad de Sevilla. CTS-547: Caracterización y optimización estadística de medicamentos; Universidad de Sevilla. CTS-1074: Inmunonutrición e inmunometabolismo
    Hydroxypropyl cellulose-methyl methacrylate and non-ionic surfactant Igepal (R) CO520 (20-25% (w/w)) have been characterized in aqueous-based dispersions for topical application systems. The systems have similar viscosity curves independent of the surfactant's concentration, showing shear-thinning fluids. Also, the elastic and viscous moduli are constant and independent of critical stress values applied; however, the storage modulus was always higher than the loss modulus. Both parameters showed a slightly dependence on the applied frequency, indicating a gel-like behavior. The complex dynamic viscosity increases until 23% (w/w) of surfactant, keeps then constant. The hardness, compressibility and adhesiveness parameters increase when increase the Igepal (R) CO520 concentration. The adhesiveness properties are 18-47% higher than the compressibility ones, with low values for hardness (similar to 0.4 N). While fracture and Hencky's strain values increase when increase the surfactant concentration, fracture work decreased, and no relation is found to deformability modulus. Also, the dispersed system with 20% (w/w) of Igepal CO520 has less stiffness than with 25% (w/w). (C) 2011 Elsevier Ltd. All rights reserved.
  • Acceso AbiertoArtículo
    Intensive care nurses' experiences during the COVID‐19 pandemic: A qualitative study
    (Wiley, 2021-09) Fernández Castillo, Rafael Jesús; González Caro, María Dolores; Fernández García, Elena; Porcel Gálvez, Ana María; Garnacho Montero, José; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS1141: Investigación Clínica Aplicada a los Cuidados y Nuevos Paradigmas Asistenciales; Universidad de Sevilla. CTS1050: Cuidados Complejos, Cronicidad y Resultados en Salud
    Background: Because of the COVID-19 pandemic, health care systems worldwide are working under challenging conditions. Patients, who are seriously ill, require intensive care admission. In fighting COVID-19, nurses are frontline health care workers and, as such, have a great responsibility providing needed specialized patient care in intensive care units (ICU). However, working conditions and emotional factors have an impact on the quality of the care provided. Aim: The purpose of the present study was to explore and describe the experiences and perceptions of nurses working in an ICU during the COVID-19 global pandemic. Study design: Qualitative research was undertaken, using an empirical approach and inductive content analysis techniques. Methods: The selected population consisted of ICU nurses from a tertiary teaching hospital in Spain. Data were obtained via semi-structured videocall interviews from Apr 12th to Apr 30th, 2020. Subsequently, transcribed verbatims were analysed using the template analysis model of Brooks. Findings: A total of 17 nurses comprised the final sample after data saturation. Four main themes emerged from the analysis and 13 subthemes: “providing nursing care,” “psychosocial aspects and emotional lability,” “resources management and safety” and “professional relationships and fellowship.” Conclusion: Providing health care by intensive care nursing professionals, during the COVID-19 pandemic, has shown both strong and weak points in the health care system. Nursing care has been influenced by fear and isolation, making it hard to maintain the humanization of the health care. Relevance to clinical practice: Implications for practice include optimizing resource management (human and material), providing psychological support, and adequate training for ICU nurses, as well as high-quality protocols for future emergency situations.
  • Acceso AbiertoArtículo
    Limitación del movimiento de flexión dorsal del tobillo en sujetos pronadores con dolor lumbar crónico
    (Elsevier Doyma, 2019) Pabón Carrasco, Manuel; Gago Reyes, Fernando; Fernández Seguín, Lourdes María; Munuera Martínez, Pedro Vicente; Palomo Toucedo, Inmaculada Concepción; Castro Méndez, Aurora; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Departamento de Podología; Universidad de Sevilla. Departamento de Fisioterapia
    Antecedentes: Estudios han relacionado la posible influencia entre los desequilibrios de la bio mecánica del pie y el dolor lumbar crónico (CLBP). Según indican algunos autores la limitación del movimiento de la flexión dorsal (FD) de la articulación tibioperonea-astragalina del pie (TPA) puede presentarse como un factor de riesgo en el dolor lumbar crónico. Objetivo: Evaluar el dolor lumbar crónico en sujetos con pies pronadores con limitación de la flexión dorsal del tobillo en al menos un pie, frente a sujetos pronadores con movilidad normal del tobillo. Material y método: estudio descriptivo transversal con muestreo por conveniencia realizado en una muestra compuesta por 126 sujetos con dolor lumbar crónico y pies pronados. Se comparó un grupo de sujetos con CLBP que presentaron limitación de la flexión dorsal de al menos un tobillo, frente a otro grupo de pronadores con CLBP y rango de movimiento normal de tobillo. Como herramientas de valoración de la variable dependiente se utilizó la escala visual analógica (EVA) y el Índice de discapacidad por dolor lumbar de Oswestry (ODI). Resultados: Se encontró correlación positiva entre la limitación de FD de la TPA en sujetos pronadores con CLBP frente al grupo de pronadores con CLBP y FD normal (EVA 4 ± 0,22; ODI: 11,85% ± 1,21). La limitación del movimiento de FD de TPA parece mostrarse como un factor de riesgo en el CLBP (EVA 5,3 ± 0,22; ODI: 17,90% ± 1,42; valor de p ODI = 0,004; EVA 0,009). Conclusiones: Se evidencia un mayor CLBP en el grupo de pronadores con limitación de FD de al menos una TPA frente al grupo de sujetos pronadores con rango normal de movimiento.
  • Acceso AbiertoArtículo
    Postprandial triglyceride-rich lipoproteins promote M1/M2 microglia polarization in a fatty-acid-dependent manner
    (Elsevier Science Inc, 2020-01) Toscano Sánchez, María del Rocío; Millán Linares, María del Carmen; Lemus Conejo, Ana; Claro Cala, Carmen María; Sánchez Margalet, Víctor; Montserrat de la Paz, Sergio; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS)
    Inhibiting M1 microglia phenotype while stimulating the M2 microglia has been suggested as a potential therapeutic approach for the treatment of neuroinflammatory diseases. Our hypothesis is that the type of dietary fatty acids (FAs) into human postprandial triglyceride-rich lipoproteins (TRLs) could modulate the plasticity of microglia. We isolated TRLs at the postprandial hypertriglyceridemic peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated FAs (SFAs), monounsaturated FAs (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated FAs. We observed that postprandial TRL-MUFAs enhance M2 microglia polarization, whereas postprandial TRL-SFAs made polarized microglia prone to an M1 phenotype. In addition, in contrast to dietary SFAs, dietary MUFAs primed for a reduced proinflammatory profile in the brain of mice fed with the different FA-enriched diets. Our study underlines a role of postprandial TRLs as a metabolic entity in regulating the plasticity of microglia and brings an understanding of the mechanisms by which dietary FAs are environmental factors fostering the innate immune responsiveness. These exciting findings open opportunities for developing nutraceutical strategies with olive oil as the principal source of MUFAs, notably oleic acid, to prevent development and progression of neuroinflammation-related diseases.
  • Acceso AbiertoArtículo
    Monounsaturated fatty acids in a high-fat diet and niacin protect from white fat dysfunction in the metabolic syndrome
    (WILEY, 2019) Montserrat de la Paz, Sergio; Naranjo, Maria C.; Millán Linares, María del Carmen; López Martín, Sergio; Abia, Rocio; Biessen, Erik A.L.; Muriana, Francisco J.G.; Bermúdez Pulgarín, Beatriz; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Biología Celular; Instituto de Biomedicina de Sevilla (IBIS); Gobierno de España; Consejo Superior de Investigaciones Científicas (CSIC); Universidad de Sevilla. CTS1074: InmunoNutrición e InmunoMetabolismo.; Universidad de Sevilla. BIO271: Expresión génica en eucariontes.; Universidad de Sevilla. BIO132: Citoquímica ultraestructural.
    Scope: Obesity is a principal causative factor of metabolic syndrome. Niacin potently regulates lipid metabolism. Replacement of saturated fatty acids by MUFAs or inclusion of omega-3 long-chain PUFAs in the diet improves plasma lipid levels. However, the potential benefits of niacin in combination with MUFAs or omega-3 long-chain PUFAs against white adipose tissue (WAT) dysfunction in the high fat diet (HFD)-induced metabolic syndrome are unknown. Methods and results: Male Lepob/ob LDLR-/- mice are fed a chow diet or HFDs based on milk cream (21% kcal), olive oil (21% kcal), or olive oil (20% kcal) plus 1% kcal from eicosapentaenoic and docosahexaenoic acids, including immediate-release niacin (1% w/v) in drinking water, for 8 weeks. Mice are then phenotyped. Dietary MUFAs are identified as positive regulators of adipose NAD+ signaling pathways by triggering NAD+ biosynthesis via the salvage pathway. This coexists with overexpression of genes involved in recognition of NAD+ and fatty acids, a surrounding lipid environment dominated by exogenous oleic acid and an alternatively activated macrophage profile, which culminate in a healthy expansion of WAT and improvement of several hallmarks that typify the metabolic syndrome. Conclusion: Niacin in combination with dietary MUFAs can favor WAT homeostasis in the development of HFD-induced obesity and metabolic syndrome.
  • Acceso AbiertoArtículo
    Effectiveness of comprehensive sexuality education to reduce risk sexual behaviours among adolescents: a systematic review
    (Mdpi Ag, 2025-01-14) Rodríguez García, Ana; Botello Hermosa, Alicia; Borrallo Riego, Álvaro; Guerra Martín, María Dolores; Universidad de Sevilla. Departamento de Enfermería; Instituto de Biomedicina de Sevilla (IBIS)
    Background: Adolescence is a critical life period marked by significant vulnerability to risky sexual behaviours. Comprehensive sex education offers better sexual and reproductive health to adolescents. Aim: We aimed to analyse the effectiveness of sex education interventions on reducing risk behaviours among adolescents. Methods: A systematic peer review was conducted. The databases consulted were PubMed, Scopus, Web of Science, and CINAHL. The inclusion criteria were as follows: randomized clinical trials published between 2013 and 2023 and methodological quality ≥ 5 points as per the Van Tulder scale. Results: A total of 255 studies were identified, with 25 finally selected. Of them, sixteen dealt with non-condom use, one was about early sexarche, and eight combined several risk behaviours. There was predominance of in-person teaching at schools with lectures and varied activities. The sample was predominantly comprised by girls aged between 14 and 16 years old. Certain variability regarding content, technique, number of sessions, duration, locus, and teaching modality and staff was observed in the com-prehensive sex education interventions. Almost all the interventions were effective in reducing risky sexual behaviours; however, two studies failed to achieve a reduction in risky sexual behaviours.
  • Acceso AbiertoArtículo
    Production, characterisation, and biological properties of Tenebrio molitor-derived oligopeptides
    (Elsevier, 2024-08-30) González de la Rosa, Teresa; Montserrat de la Paz, Sergio; Rivero-Pino, Fernando; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Ciencia e Innovación, Gobierno de España; Universidad de Sevilla. CTS-1074: Inmunonutrición e Inmunometabolismo
    Three protein hydrolysates from Tenebrio molitor were obtained by enzymatic hydrolysis employing two food-grade proteases (i.e. Alcalase and Flavourzyme), and a complete characterisation of their composition was done. The digestion-derived products were obtained using the INFOGEST protocol. In vitro antioxidant activity and anti-inflammatory activities were evaluated. Tenebrio molitor flour and the protein hydrolysates showed a high ability to scavenge the DPPH radical (EC50 values from 0.30 to 0.87 mg/mL). The hydrolysate obtained with a combination of the two food-grade proteases could decrease the gene expression of pro-inflammatory genes after being digested. Furthermore, the peptidome was fully determined for the first time for T. molitor hydrolysates and digests, and 40 peptides were selected based on their bioactivity to be evaluated by in silico tools, including prediction tools and molecular docking. These results provide new perspectives on the use of edible insects as sustainable and not nutritionally disadvantageous food for human consumption.
  • Acceso AbiertoArtículo
    Digital pain extent is associated with pain intensity but not with pain-related cognitions and disability in people with chronic musculoskeletal pain: a cross-sectional study
    (BMC (BioMed Central), 2022-07-30) Luque-Suárez, Alejandro; Falla, Deborah; Barbero, Marco; Pineda-Galán, Consolación; Marco, Derboni; Giuffrida, Vincenzo; Martínez Calderón, Javier; Universidad de Sevilla. Departamento de Fisioterapia; Instituto de Biomedicina de Sevilla (IBIS); University of Malaga; Universidad de Sevilla. CTS-1110: Understanding Movement & Self in health from Science
    Background: To evaluate whether digital pain extent is associated with an array of psychological factors such as optimism, pessimism, expectations of recovery, pain acceptance, and pain self-efficacy beliefs as well as to analyse the association between digital pain extent and pain intensity and pain-related disability in people with chronic musculoskeletal pain. Methods: A descriptive cross-sectional study conducted in a primary health care setting was carried out including 186 individuals with chronic musculoskeletal pain. Patient-reported outcomes were used to assess psychological factors, pain intensity, and pain-related disability. Digital pain extent was obtained from pain drawings shaded using a tablet and analysed using novel customized software. Multiple linear regression models were conducted to evaluate the association between digital pain extent and the aforementioned variables. Results: Digital pain extent was statistically significantly associated with pain intensity. However, digital pain extent was not associated with any psychological measure nor with pain-related disability. Discussion: The results did not support an association between digital pain extent and psychological measures.
  • Acceso AbiertoArtículo
    Nursing students’ experiences about clinical practice tutoring: a cross-sectional observational study
    (MDPI, 2024-12-13) Borrallo Riego, Álvaro; Magni, Eleonora; Pérez Jiménez, José Miguel; Guerra Martín, María Dolores; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. CTS-969: Innovación en cuidados y determinantes sociales en salud; Universidad de Sevilla. CTS-1149: Salud integral y sostenible: enfoque Bio-psico-social, Cultural y Espiritual para el Desarrollo Humano
    Objective: Nursing students’ experiences about clinical practice tutoring in a public university from southern Spain and at its two attached educational centres were analysed. Methods: A cross-sectional observational study was carried out. The population was comprised of nursing students attending their fourth year of university during the 2023/2024 academic period, with a final sample of 179 subjects. Sociodemographic data were collected and a validated questionnaire on opinions about the figure of clinical practice tutors was applied, with 34 closed questions offering five answer options. The questions were categorized into 17 dimensions. A question on the students’ satisfaction with tutoring of the practices was included, in addition to an open question to gather the students’ comments and/or suggestions in relation to clinical practice tutoring. The analysis was performed through a data matrix in SPSS. The Kruskal–Wallis test was used to compare the centres according to the questionnaire dimensions, considering p-values < 0.05 to establish statistically significant differences. The open question was analysed using Atlas.ti. Results: Most of the students were women, with an approximate mean age of 23 years old. Significant differences were detected among the centres in almost all dimensions from the questionnaire. High satisfaction levels were obtained in the three centres. A total of 83 verbatims were collected in the open question and grouped into eight categories. Conclusion: Nursing students place significant importance on the role of the clinical tutor. Clinical tutors who demonstrate enthusiasm for teaching, foster a positive environment based on active listening, respect, and the encouragement of autonomy, are essential to enhancing the students’ experience during clinical placements.
  • Acceso AbiertoArtículo
    Molecular and Phylogenetic Characterization of the Monkeypox Outbreak in the South of Spain
    (John Wiley & Sons, 2024) Casimiro Soriguer, C. S.; Pérez Florido, J.; Lara, M.; Camacho Martínez, P.; Merino Díaz, L.; Pupo Ledo, I.; de Salazar, A.; Fuentes, A.; Vinuela, L.; Chueca, N.; Lepe Jiménez, José Antonio; Garcia, F.; Universidad de Sevilla. Departamento de Microbiología; Ministerio de Ciencia e Innovación (MICIN). España; Instituto de Salud Carlos III
    Background and Aim: Until the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain. Methods: Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Results: Whole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment.
  • Acceso AbiertoArtículo
    Activity of Cefiderocol and Innovative β-lactam/β-lactamase Inhibitor Combinations Against Isogenic Strains of Escherichia Coli Expressing Single and Double β-lactamases under High and Low Permeability Conditions
    (Elsevier, 2024) Blanco Martín, Tania; Alonso García, Isaac; González Pinto, Lucía; Outeda García, Michelle; Guijarro Sánchez, Paula; López Hernández, Inmaculada; Pérez Vázquez, María; Aracil, Belén; López Cerero, Lorena; Fraile Ribot, Pablo; Arca Suárez, Jorge; Universidad de Sevilla. Departamento de Microbiología; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC); Red de Investigación en Enfermedades Infecciosas (REIPI); Xunta de Galicia
    Objectives: To analyse the impact of the most clinically relevant β-lactamases and their interplay with low outer membrane permeability on the activity of cefiderocol, ceftazidime/avibactam, aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/xeruborbactam and meropenem/nacubactam against recombinant Escherichia coli strains. Methods: We constructed 82 E. coli laboratory transformants expressing the main β-lactamases circulating in Enterobacterales (70 expressing single β-lactamase and 12 producing double carbapenemase) under high (E. coli TG1) and low (E. coli HB4) permeability conditions. Antimicrobial susceptibility testing was determined by reference broth microdilution. Results: Aztreonam/avibactam, cefepime/zidebactam, cefiderocol, meropenem/xeruborbactam and meropenem/nacubactam were active against all E. coli TG1 transformants. Imipenem/relebactam, meropenem/vaborbactam, cefepime/taniborbactam and cefepime/enmetazobactam were also highly active, but unstable against most of MBL-producing transformants. Combination of β-lactamases with porin deficiency (E. coli HB4) did not significantly affect the activity of aztreonam/avibactam, cefepime/zidebactam, cefiderocol or meropenem/nacubactam, but limited the effectiveness of the rest of carbapenem- and cefepime-based combinations. Double-carbapenemase production resulted in the loss of activity of most of the compounds tested, an effect particularly evident for those E. coli HB4 transformants in which MBLs were present. Conclusions: Our findings highlight the promising activity that cefiderocol and new β-lactam/β-lactamase inhibitors have against recombinant E. coli strains expressing widespread β-lactamases, including when these are combined with low permeability or other enzymes. Aztreonam/avibactam, cefiderocol, cefepime/zidebactam and meropenem/nacubactam will help to mitigate to some extent the urgency of new compounds able to resist MBL action, although NDM enzymes represent a growing challenge against which drug development efforts are still needed.
  • Acceso AbiertoArtículo
    Fibroblast Growth Factor 21 is a Hepatokine involved in MASLD Progression
    (John Wiley & Sons, 2024) Gallego Durán, Rocío; Ampuero Herrojo, Javier; Maya Miles, Douglas; Pastor Ramírez, Helena; Montero Vallejo, Rocío; Rivera Esteban, Jesús; Álvarez Amor, Leticia; Pareja, María Jesús; Rico, María Carmen; Millán, Raquel; Muñoz Hernández, Rocío; Romero Gómez, Manuel; Universidad de Sevilla. Departamento de Fisiología; Universidad de Sevilla. Departamento de Medicina; Junta de Andalucía; Instituto de Salud Carlos III; Ministerio de Economía y Competitividad (MINECO). España
    Aim: We aimed to assess the role of FGF21 in metabolic dysfunction-associated steatotic liver disease (MASLD) at a multi-scale level. Methods: We used human MASLD pathology samples for FGF21 gene expression analyses (qPCR and RNAseq), serum to measure circulating FGF21 levels and DNA for genotyping the FGF21 rs838133 variant in both estimation and validation cohorts. A hepatocyte-derived cell line was exposed to free fatty acids at different timepoints. Finally, C57BL/6J mice were fed a high-fat and choline-deficient diet (CDA-HFD) for 16 weeks to assess hepatic FGF21 protein expression and FGF21 levels by ELISA. Results: A significant upregulation in FGF21 mRNA expression was observed in the liver analysed by both qPCR (fold change 5.32 ± 5.25 vs. 0.59 ± 0.66; p = 0.017) and RNA-Seq (3.5 fold; FDR: 0.006; p < 0.0001) in MASLD patients vs. controls. Circulating levels of FGF21 were increased in patients with steatohepatitis vs. bland steatosis (386.6 ± 328.9 vs. 297.9 ± 231.5 pg/mL; p = 0.009). Besides, sex, age, A-allele from FGF21, GG genotype from PNPLA3, ALT, type 2 diabetes mellitus and BMI were independently associated with MASH and significant fibrosis in both estimation and validation cohorts. In vitro exposure of Huh7.5 cells to high concentrations of free fatty acids (FFAs) resulted in overexpression of FGF21 (p < 0.001). Finally, Circulating FGF21 levels and hepatic FGF21 expression were found to be significantly increased (p < 0.001) in animals under CDA-HFD. Conclusions: Hepatic and circulating FGF21 expression was increased in MASH patients, in Huh7.5 cells under FFAs and in CDA-HFD animals. The A-allele from the rs838133 variant was also associated with an increased risk of steatohepatitis and significant and advanced fibrosis in MASLD patients.
  • EmbargoArtículo
    Cortical hypometabolism in Parkinson’s disease is linked to cholinergic basal forebrain atrophy
    (Springer, 2024) Labrador-Espinosa, Miguel Á.; Silva-Rodríguez, Jesús; Okkels, Niels; Muñoz-Delgado, Laura; Horsager, Jacob; Castro-Labrador, Sandra; Franco-Rosado, Pablo; Castellano-Guerrero, Ana María; Iglesias Camacho, Elena; San-Eufrasio, Manuela; Macías-García, Daniel; Jesús, Silvia; Adarmes-Gómez, Astrid; Ojeda-Lepe, Elena; Carrillo, Fátima; Martín Rodríguez, Juan Francisco; Roldán Lora, Florinda; García Solís, David; Borghammer, Per; Mir Rivera, Pablo; Grothe, Michel J.; Universidad de Sevilla. Departamento de Psicología Experimental; Universidad de Sevilla. Departamento de Medicina; Ministerio de Ciencia e Innovación (MICIN). España; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Fundación Alicia Koplowitz
    Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson’s disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [18F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment. We further assessed the spatial correspondence of the cortical pattern of cBF-associated hypometabolism with the pattern of cholinergic denervation in PD as assessed by [18F]FEOBV-PET imaging of presynaptic cholinergic terminal density in a second cohort. Lower volume of the cortically-projecting posterior cBF, but not of the anterior cBF, was significantly associated with extensive neocortical hypometabolism [p(FDR) < 0.05], which mediated the association between cBF atrophy and cognitive impairment (mediated proportion: 43%, p < 0.001). In combined models, posterior cBF atrophy explained more variance in cortical hypometabolism (R2 = 0.26, p < 0.001) than local atrophy in the cortical areas themselves (R2 = 0.16, p = 0.01). Topographic correspondence analysis with the [18F]FEOBV-PET pattern revealed that cortical areas showing most pronounced cBF-associated hypometabolism correspond to those showing most severe cholinergic denervation in PD (Spearman’s ρ = 0.57, p < 0.001). In conclusion, posterior cBF atrophy in PD is selectively associated with hypometabolism in denervated cortical target areas, which mediates the effect of cBF atrophy on cognitive impairment. These data provide first-time in-vivo evidence that cholinergic degeneration represents a principle pathological correlate of cortical hypometabolism underlying cognitive impairment in PD.
  • Acceso AbiertoArtículo
    Analysis of dry needling combined with an exercise program in the treatment of knee osteoarthritis: A randomized clinical trial
    (MDPI, 2024-11-26) Agost-González, Aida; Escobio Prieto, Isabel; Barrios-Quinta, Cristo Jesús; Cardero-Durán, María de los Ángeles; Espejo-Antúnez, Luis; Albornoz Cabello, Manuel; Universidad de Sevilla. Departamento de Fisioterapia; Universidad de Sevilla. CTS-1137: NEUROPhysiUS - Neurological Physiotherapy, Innovative Neurorehabilitation and Neurodevelopmental Disorders; Universidad de Sevilla. CTS-947: Salud y actividad física para calidad de vida
    Background: Therapeutic exercise is recommended for people with knee osteoarthritis (OA), although it could be complemented with other treatments such as dry needling (DN). The purpose of this study was to evaluate and compare the resulting data on pain, functionality, strength and range of motion in subjects with knee osteoarthritis after being treated with a specific therapeutic physical exercise program alone or in combination with the DN technique in the popliteus muscle. Methods: A total of 33 participants were randomly assigned to two groups: the dry needling plus therapeutic physical exercise group (n = 15) and the therapeutic physical exercise alone group (n = 18). Both groups received the same exercise protocol, and the dry-needling group conducted three sessions of this technique over 3 weeks. Results: Variables such as pain, functionality, neuropathic pain, stiffness, strength, range of motion, pain catastrophizing and kinesiophobia were evaluated before and after the intervention, as well as at a follow-up 3 months after the intervention. Significant differences were observed between the two groups in pain intensity, stiffness, functionality, pain catastrophizing and kinesiophobia (p < 0.001). Conclusions: The combination of dry needling targeting the popliteus muscle and therapeutic physical exercise showed better results in terms of pain, functionality and strength compared to therapeutic physical exercise alone, especially after the intervention.