Neuropathic pain induced by sciatic nerve injury involves epigenetic changes and chromatolytic damage in the somatosensory nervous system. Effects of miR-30c-5p gain and loss of function.

ABSTRACT: Neuropathic pain (NP) is a debilitating chronic syndrome that is often refractory to currently available analgesics. The maintenance of NP encompasses long term pathological plasticity in the nervous system that may be explained by alterations in the epigenetic mechanisms and cellular processes that underlie this disease. In this thesis, we investigated the involvement of epigenetic mechanisms in neuropathic pain establishment and chronification and the effects of modulating miR-30c-5p in the somatosensory nervous system. The transcript levels of DNA methyltransferase-3A and 3B were significantly up-regulated in the spinal dorsal horn and dorsal root ganglia from neuropathic rats. This upregulation was potentiated when neuropathic rats were treated with a miR-30c-5p inhibitor. In parallel, both structures exhibited increased methylation at cytosine in CpG islands. By luciferase assay, we demonstrated a post-transcriptional regulation for DNMT3B and DNMT3A by miR-30c-5p. Furthermore, we demonstrated that NP induces an increase in the chromatolytic damage suffered by DRG neurons. This phenomenon was potentiated when neuropathic rats were treated with a miR-30c-5p mimic. We showed that miR-30c-5p treatment induces reorganization and loss of nucleolar transcription units, segregation of dense fibrillar and granular components and a depletion of cajal bodies. We propose that miR-30c-5p modulation in NP plays an essential role in the epigenetic mechanism and cellular processes that underlie this disease.Esta tesis ha sido financiada con ayudas a la investigación procedentes de: - Beca predoctoral de Neurociencia: Fundación Tatiana Pérez de Guzmán el Bueno. - Instituto de investigación sanitaria Marqués de Valdecilla - Ministerio de Economía y Competitividad a través de los Proyectos del Plan Estatal: SAF2013-47434-R y SAF2016-77732-

Desarrollo de los Recursos Humanos. Planes de acción para la recolocación

El trabajo trata sobre los planes de recolocación que las empresas, a raíz de la reforma laboral, tienen que ofrecer a sus trabajadores en caso de despido siempre que el nº de personas que salen de la empresa sea superior a 50. Desde la estrategia de la empresa, pasando por la funcional de los recursos humanos, el trabajo define todas las políticas de RR.HH, hasta llegar a la formación, donde, después de explicar todo el desarrollo de esta función política en la empresa, añade la formación para la recolocación caracterizada porque se imparte cuando el empleado deja de pertenecer a la empresaGrado en Relaciones Laborales y Recursos Humano

Systematic review of cancer research treatments

:ntroduction. Given the prevalence and socioeconomic impact of cancer, research in all its aspects is of vital importance, and it requires a prior evaluation of the available scientific information. Methods. A systematic review of information on investigational cancer treatments in Europe over the last ten years was carried out. Results. The investigations included can be classified and analyzed according to the type of study, type of cancer, type of treatment, aspects evaluated, geographic location and language of publication. The methodological quality of the included CTs was assessed according to the Jadad scale. Conclusions. Seven types of scientific investigations were analyzed. The majority were CT with a score ≥3 (out of 5) on the Jadad scale. Most referred to breast and prostate cancers, and pharmacological and immunological treatments. Safety and efficacy were preferably studied. They were carried out mainly in regions of Central, Western and Southern Europe, and they were published in EnglishIntroducción. Dada la prevalencia y el impacto socioeconómico del cáncer, es de vital importancia la investigación en todas sus vertientes, que requiere una evaluación previa de la información científica disponible. Métodos. Se realizó una revisión sistemática de la información referente a tratamientos en investigación sobre el cáncer en Europa en los últimos diez años. Resultados. Las investigaciones incluidas pueden clasificarse y analizarse según tipo de estudio, tipo de cáncer, tipo de tratamiento, aspectos evaluados, localización geográfica e idioma de publicación. Se evaluó la calidad metodológica de los EC incluidos de acuerdo con la escala de Jadad. Conclusiones. Se analizaron siete tipos de investigaciones científicas. La mayoría fueron EC con una puntuación ≥3 (sobre 5) en la escala de Jadad. Mayormente se referían a cánceres de mama y próstata, y tratamientos de tipo farmacológico e inmunológico. Se estudió preferentemente seguridad y eficacia. Se llevaron a cabo sobre todo en regiones del centro, oeste y sur de Europa, y se publicaron en inglés

¿Cuándo viene tu padre?

El objeto de estudio es conocer los factores migratorios (económico, social y medioambiental) a través de una metodología basada en problemas, en concreto mediante una situación vivida por el alumnado: la emigración de sus padres hacia Inglaterra por motivos laborales y económicos. Consideramos que la citada metodología abre un amplio abanico de posibilidades en la didáctica de las Ciencias Sociales, de igual modo que la naturaleza de esta área favorece la interdisciplinariedad entre materias y una aproximación hacia el problema social presente en Vilamarxant, España y Europa

Impact of Maturation and Vitrification Time of Human GV Oocytes on the Metaphase Plate Configuration

The combination of in vitro maturation (IVM) techniques and oocyte vitrification (OV) could increase the number of useful oocytes in different types of patients. IVM and subsequent OV is the most widely used clinical strategy. Would the results improve if we reverse the order of the techniques? Here, we evaluated survival, in vitro maturation, time to extrude the first polar body (PB), and the metaphase plate configuration of human prophase I (GV) oocytes before or after their vitrification. Specific, 195 GV oocytes from 104 patients subjected to controlled ovarian stimulation cycles were included. We stablished three experimental groups: GV oocytes vitrified and IVM (Group GV-Vit), GV oocytes IVM and vitrified at MII stage (Group MII-Vit), and GV oocytes IVM (Group not-Vit). All of them were in vitro matured for a maximum of 48 h and fixed to study the metaphase plate by confocal microscopy. According to our results, the vitrification of immature oocytes and their subsequent maturation presented similar survival, maturation, and metaphase plate conformation rates, but a significantly higher percentage of normal spindle than the standard strategy. Additionally, the extension of IVM time to 48 h did not seem to negatively affect the oocyte metaphase plate configuration.This research was funded by Department of Biotechnology of the University of Alicante (VIGROB-186)

Identification of Epigenetic Interactions between MicroRNA-30c-5p and DNA Methyltransferases in Neuropathic Pain

Neuropathic pain is a prevalent and severe chronic syndrome, often refractory to treatment, whose development and maintenance may involve epigenetic mechanisms. We previously demonstrated a causal relationship between miR-30c-5p upregulation in nociception-related neural structures and neuropathic pain in rats subjected to sciatic nerve injury. Furthermore, a short course of an miR-30c-5p inhibitor administered into the cisterna magna exerts long-lasting antiallodynic effects via a TGF-?1-mediated mechanism. Herein, we show that miR-30c-5p inhibition leads to global DNA hyper-methylation of neurons in the lumbar dorsal root ganglia and spinal dorsal horn in rats subjected to sciatic nerve injury. Specifically, the inhibition of miR-30-5p significantly increased the expression of the novo DNA methyltransferases DNMT3a and DNMT3b in those structures. Furthermore, we identified the mechanism and found that miR-30c-5p targets the mRNAs of DNMT3a and DNMT3b. Quantitative methylation analysis revealed that the promoter region of the antiallodynic cytokine TGF-?1 was hypomethylated in the spinal dorsal horn of nerve-injured rats treated with the miR-30c-5p inhibitor, while the promoter of Nfyc, the host gene of miR-30c-5p, was hypermethylated. These results are consistent with long-term protection against neuropathic pain development after nerve injury. Altogether, our results highlight the key role of miR-30c-5p in the epigenetic mechanisms' underlying neuropathic pain and provide the basis for miR-30c-5p as a therapeutic target.Funding: This work was supported by: Grant SAF2016-77732-R funded by MCIN/AEI/10.13039/ 501100011033 and by “ERDF A way of making Europe”; Grant PID2019-104398RB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and Instituto de Investigación Sanitaria Valdecilla (IDIVAL) (NVAL17/23). R.F. was the recipient of a pre-doctoral fellowship of the Foundation Tatiana Pérez de Guzmán el Bueno. Acknowledgments: We acknowledge the excellent technical assistance of Nieves García Iglesias

Development and Validation of a Clinical-Genetic Risk Score to Predict Hepatic Encephalopathy in Patients With Liver Cirrhosis

[Introduction] We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score.[Methods] Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS.[Results] Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15–1.48], P < 0.001), albumin (sHR 0.90 [0.86–0.93], P < 0.001), genetic score (sHR 1.90 [1.57–2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57–4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low-risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high-risk group.[Discussion] The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score, which combined genetic background together with albumin, bilirubin, and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis.Peer reviewe

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects

[Background and Aim] Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD).[Methods] Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years).[Results] Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these.[Conclusions] The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.This project has been partially funded by the ‘Consejería de Salud de la Junta de Andalucía’ (PI-0075-2014) and the ‘Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI17/00535 and GLD19/00100).Peer reviewe

SIGNA-UNI: Jornadas sobre tecnología de la información para una universidad accesible

Es una aplicación en formato DVD interactivo y App para Android. Ambas versiones son accesibles y gratuitas y han sido creadas por la UV en colaboración con Fundación Vodafone España. Su objetivo es facilitar la comunicación del personal de la comunidad universitaria. Este material está compuesto por una serie de términos y frases en Lengua de Signos que se suelen utilizar con más frecuencia en diferentes ámbitos universitarios. Los videos han sido validados por el personal especialista de la Fesord CV y por los técnicos de la UPD. Aplicación Android, disponible en Google Play

Gut bacterial DNA translocation is an independent risk factor of flare at short term in patients with crohn's disease

OBJECTIVES We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-α levels and a higher percentage of patients on intensified anti-TNF therapy. CONCLUSIONS BactDNA is an independent risk factor of relapse at 6 months in CD patients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation