Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Estudio de la respuesta inmunológica humoral tras la vasectomía y sus consecuencias sobre la salud del individuo / María Dolores Egea Romero ; directores Juan José Parrilla Paricio, Pedro González Martínez.

Tesis-Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 459.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M.-1350

Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation

Galantamine is a drug currently used to treat Alzheimer’s disease (AD); in this group of patients it has been observed that concomitant ischemic brain injury can accelerate their cognitive deficit. We have previously shown that galantamine can afford neuroprotection on in vitro and in vivo models related to brain ischemia. In this context, this study was planned to investigate the intracellular signaling pathways implicated in the protective effect of galantamine on an in vitro brain ischemia-reperfusion model, namely rat hippocampal slices subjected to oxygen and glucose deprivation (OGD) followed by reoxygenation. Galantamine protected hippocampal slices subjected to OGD in a concentration-dependent manner; at 15 mM, cell death was reduced to almost control levels. The neuroprotective effects of galantamine were reverted by mecamylamine and AG490, but not by atropine, indicating that nicotinic receptors and Jak2 participated in this action. Galantamine also prevented p65 translocation into the nucleus induced by OGD; this effect was also linked to nicotinic receptors and Jak2. Furthermore, galantamine reduced iNOS induction and production of NO caused by OGD via Jak2. ROS production by NADPH oxidase (NOX) activation was also inhibited by galantamine. In conclusion, galantamine afforded neuroprotection under OGD-reoxygenation conditions by activating a signaling pathway that involves nicotinic receptors, Jak2 and the consequent inhibition of NOX and NFkB/iNOS.Instituto de Salud Carlos IIIFundación Teófilo HernandoMinisterio de Ciencia e InnovaciónAgencia Lain EntralgoFundación C.I.E.N.Depto. de Bioquímica y Biología MolecularFac. de FarmaciaTRUEpu

Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by α7 and β2* nicotinic stimulation

A good model of neuronal death that reproduces the characteristic tau (τ) hyperphosphorylation of Alzheimeŕs disease is the use of okadaic acid (OA). The aim of this study was to determine the contribution of α7 and β2* nicotinic acetylcholine receptor (nAChR) subtypes to neuroprotection against OA in the SHSY5Y cell line by using the selective α7 and β2* nAChR agonists PNU 282987 and 5-Iodo-A85380, respectively. The results of this study show that both α7 and β2* nAChR can afford neuroprotection against OA-induced neurotoxicity. Protection mediated by α7 nAChRs was independent of Ca and involved the intracellular signaling pathway Janus Kinase-2/Phosphatidylinositol-3-kinase/Akt. When Ca entry was promoted through the α7 nAChR by using the α7-selective positive allosteric modulator PNU 120596, protection was lost. By contrast, protection mediated by β2* nAChRs was Ca dependent and implicated the signaling pathways PI3K/Akt and extracellular regulated kinase 1/2. Both α7 and β2* nAChR activation converged on downregulation of GSK-3β and reduction of τ phosphorylation in cells undergoing cell death induced by OA. Therefore, targeting nAChR could offer a strategy for reducing neurodegeneration secondary to hyperphosphorylation of protein τ.Fundación Teófilo Hernand

Neurotoxicity Induced by Okadaic Acid in the Human Neuroblastoma SH-SY5Y Line Can Be Differentially Prevented by α7 and β2* Nicotinic Stimulation

A good model of neuronal death that reproduces the characteristic tau (τ) hyperphosphorylation of Alzheimeŕs disease is the use of okadaic acid (OA). The aim of this study was to determine the contribution of α7 and β2* nicotinic acetylcholine receptor (nAChR) subtypes to neuroprotection against OA in the SH-SY5Y cell line by using the selective α7 and β2* nAChR agonists PNU 282987 and 5-Iodo-A85380, respectively. The results of this study show that both α7 and β2* nAChR can afford neuroprotection against OA-induced neurotoxicity. Protection mediated by α7 nAChRs was independent of Ca2+ and involved the intracellular signaling pathway Janus Kinase-2/Phosphatidylinositol-3-kinase/Akt. When Ca2+ entry was promoted through the α7 nAChR by using the α7-selective positive allosteric modulator PNU 120596, protection was lost. By contrast, protection mediated by β2* nAChRs was Ca2+ dependent and implicated the signaling pathways PI3K/Akt and extracellular regulated kinase 1/2. Both α7 and β2* nAChR activation converged on downregulation of GSK-3β and reduction of τ phosphorylation in cells undergoing cell death induced by OA. Therefore, targeting nAChR could offer a strategy for reducing neurodegeneration secondary to hyperphosphorylation of protein τ.Spanish Ministry of Science and Innovation (SAF2009-12150); Spanish Ministry of Health-Instituto de Salud Carlos III (RETICS-RD06/0026); Comunidad Autónoma de Madrid (SAL2006/0275 to M.G.L., MH63631, GM48677 to J.M.M.).Peer reviewe

ITH12410/SC058: A New Neuroprotective Compound with Potential in the Treatment of Alzheimer's Disease

The neuroprotective profile of the dibenzothiadiazepine ITH12410/SC058 (2-chloro-5,6-dihydro-5,6-diacetyldibenzo[b,f ]-[1,4,5]thiadiazepine) against several neurotoxicity models related to neurodegenerative diseases is herein described. ITH12410/SC058 protected SH-SY5Y cells against the loss of cell viability elicited by amyloid beta peptide and okadaic acid, a selective inhibitor of phosphoprotein phosphatase 2A that induces neurofibrillary tangle formation. Furthermore, ITH12410/SC058 is neuroprotective against several in vitro models of oxidative stress, that is, H2O2 exposure or incubation with rotenone plus oligomycin A in SH-SY5Y cells, and oxygen and glucose deprivation followed by reoxygenation in rat hippocampal slices. By contrast, ITH12410/SC058 was unable to significantly protect SH-SY5Y neuroblastoma cells against the toxicity elicited by Ca2+ overload. Our results confirm the hypothesis that the dibenzothiadiazepine ITH12410/SC058 features its neuroprotective actions in a multitarget fashion, and is a promising drug for the treatment of neurodegenerative diseases.Peer Reviewe

Intervención educativa en el alumnado con necesidades educativas especiales en la educación secundaria

Resumen basado en el de la publicaciónOrientadores educativos de centros de educación secundaria, que participaron en el Seminario de Coordinación Institucional de los Servicios de Orientación Educativa en Educación Secundaria de la Región de Murcia organizado por la Consejería de Educación, Formación y Empleo, pretenden facilitar, ordenar y mejorar el desarrollo de las medidas y actuaciones al amparo del Decreto 359/2009, de 30 de octubre, por el que se establece y regula la respuesta educativa a la diversidad del alumnado en la Comunidad Autónoma de la Región de Murcia. Se tiene que hacer efectiva una respuesta educativa de calidad al alumnado con necesidades educativas especiales y para ello se facilita una definición y se dan orientaciones para cada una de las actuaciones generales y medidas ordinarias, así como se desarrollan con detalle las medidas específicas. Se aporta información imprescindible para el seguimiento y evaluación de este alumnado incluyendo algunos anexos que pueden facilitar estas tareas, y finalmente se aportan unos cuadros de cada una de las discapacidades y dificultades más frecuentes en los centros de educación secundaria, que facilitan de manera clara y eficaz una intervención educativa de calidad para cada uno de estos perfiles de alumnado. Denota un ejercicio profesional comprometido y que responde a un deseo de mejorar la atención educativa y la calidad de vida del alumnado con necesidades educativas especiales escolarizado en los centros de educación secundaria de la Comunidad Autónoma de Murcia.Murcia: Consejería de Educación. Secretaría General, Servicio de Publicaciones y Estadística; Avenida de La Fama, 15. 30006 Murcia; Teléfono 968 279842; Fax: 968 27 98 35; [email protected]; http://www.educarm.es/publicacionesES

Both Creatine and Its Product Phosphocreatine Reduce Oxidative Stress and Afford Neuroprotection in an <i>In Vitro</i> Parkinson’s Model

Creatine is the substrate for creatine kinase in the synthesis of phosphocreatine (PCr). This energetic system is endowed of antioxidant and neuroprotective properties and plays a pivotal role in brain energy homeostasis. The purpose of this study was to investigate the neuroprotective effect of creatine and PCr against 6-hydroxydopamine (6-OHDA)-induced mitochondrial dysfunction and cell death in rat striatal slices, used as an in vitro Parkinson’s model. The possible involvement of the signaling pathway mediated by phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase-3β (GSK3β) was also evaluated. Exposure of striatal slices to 6-OHDA caused a significant disruption of the cellular homeostasis measured as 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction, lactate dehydrogenase release, and tyrosine hydroxylase levels. 6-OHDA exposure increased the levels of reactive oxygen species and thiobarbituric acid reactive substances production and decreased mitochondrial membrane potential in rat striatal slices. Furthermore, 6-OHDA decreased the phosphorylation of Akt (Serine473) and GSK3β (Serine9). Coincubation with 6-OHDA and creatine or PCr reduced the effects of 6-OHDA toxicity. The protective effect afforded by creatine or PCr against 6-OHDA-induced toxicity was reversed by the PI3K inhibitor LY294002. In conclusion, creatine and PCr minimize oxidative stress in striatum to afford neuroprotection of dopaminergic neurons. Depto. de Bioquímica y Biología MolecularFac. de FarmaciaTRUEpu

ITH12410/SC058: A New Neuroprotective Compound with Potential in the Treatment of Alzheimer’s Disease

The neuroprotective profile of the dibenzothiadiazepine ITH12410/SC058 (2-chloro-5,6-dihydro-5,6-diacetyldibenzo[b,f][1,4,5]thiadiazepine) against several neurotoxicity models related to neurodegenerative diseases is herein described. ITH12410/SC058 protected SH-SY5Y cells against the loss of cell viability elicited by amyloid beta peptide and okadaic acid, a selective inhibitor of phosphoprotein phosphatase 2A that induces neurofibrillary tangle formation. Furthermore, ITH12410/SC058 is neuroprotective against several in vitro models of oxidative stress, that is, H2O2 exposure or incubation with rotenone plus oligomycin A in SH-SY5Y cells, and oxygen and glucose deprivation followed by reoxygenation in rat hippocampal slices. By contrast, ITH12410/SC058 was unable to significantly protect SH-SY5Y neuroblastoma cells against the toxicity elicited by Ca2+ overload. Our results confirm the hypothesis that the dibenzothiadiazepine ITH12410/SC058 features its neuroprotective actions in a multitarget fashion, and is a promising drug for the treatment of neurodegenerative diseasesInstituto de Salud Carlos IIIMinisterio de Ciencia, Innovación y Universidades (España)Ministerio de Economía, Comercio y Empresa (España)Depto. de Bioquímica y Biología MolecularFac. de FarmaciaFALSEpu