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Study of protein expresion [sic] in peri-infarct tissue after cerebral ischemia

In this work, we report our study of protein expression in rat peri-infarct tissue, 48 h after the induction of permanent focal cerebral ischemia. Two proteomic approaches, gel electrophoresis with mass spectrometry and combined fractional diagonal chromatography (COFRADIC), were performed using tissue samples from the periphery of the induced cerebral ischemic lesions, using tissue from the contra-lateral hemisphere as a control. Several protein spots (3408) were identified by gel electrophoresis, and 11 showed significant differences in expression between peri-infarct and contralateral tissues (at least 3-fold, p < 0.05). Using COFRADIC, 5412 proteins were identified, with 72 showing a difference in expression. Apart from blood-related proteins (such as serum albumin), both techniques showed that the 70 kDa family of heat shock proteins were highly expressed in the peri-infarct tissue. Further studies by 1D and 2D western blotting and immunohistochemistry revealed that only one member of this family (the inducible form, HSP72 or HSP70i) is specifically expressed by the peri-infarct tissue, while the majority of this family (the constitutive form, HSC70 or HSP70c) is expressed in the whole brain. Our data support that HSP72 is a suitable biomarker of peri-infarct tissue in the ischemic brain

Experience in the Use of Social Media in Medical and Health Education

Objectives: Social media are online tools that allow collaboration and community building. Succinctly, they can be described as applications where “users add value”. This paper aims to show how five educators have used social media tools in medical and health education to attempt to add value to the education they provide. Methods: We conducted a review of the literature about the use of social media tools in medical and health education. Each of the authors reported on their use of social media in their educational projects and collaborated on a discussion of the advantages and disadvantages of this approach to delivering educational projects. Results: We found little empirical evidence to support the use of social media tools in medical and health education. Social media are, however, a rapidly evolving range of tools, websites and online experiences and it is likely that the topic is too broad to draw definitive conclusions from any particular study. As practitioners in the use of social media, we have recognised how difficult it is to create evidence of effectiveness and have therefore presented only our anecdotal opinions based on our personal experiences of using social media in our educational projects. Conclusion: The authors feel confident in recommending that other educators use social media in their educational projects. Social media appear to have unique advantages over non-social educational tools. The learning experience appears to be enhanced by the ability of students to virtually build connections, make friends and find mentors. Creating a scientific analysis of why these connections enhance learning is difficult, but anecdotal and preliminary survey evidence appears to be positive and our experience reflects the hypothesis that learning is, at heart, a social activity

Evaluación del tiempo de espera óptimo para la colocación de implantes dentales tras elevaciones de seno maxilar (ESM) con un injerto compuesto por hueso autólogo y biomaterial

Objetivo: Evaluar el tiempo de espera óptimo para la colocación de implantes dentales tras elevaciones de seno maxilar (ES) con un injerto compuesto con la misma cantidad de hueso autólogo que de biomaterial, a través de biopsias humanas, comparando el hueso regenerado obtenido a los 4-5 meses con el obtenido a los 6-8 meses, teniendo el hueso nativo como referencia. Material y Métodos: Fueron analizadas un total de 26 biopsias de 11 pacientes tras ES. Se crearon dos grupos dependiendo del momento de la colocación del implante: grupo t1 a los 4-5 meses (n=13) y grupo t2 a los 6-8 meses (n=13). Fue analizado por microtomografía computarizada (MicroCT) para cada biopsia el mismo volumen para el hueso injertado que para el nativo. Resultados: Se encontraron diferencias estadísticamente significativas en la densidad mineral ósea (BMD), fracción de volumen óseo y separación trabecular (Tb.Sp) entre el hueso nativo e injertado en los grupos t1 y t2, mostrando valores más altos en el hueso injertado excepto para la variable Tb.Sp. que sucedió a la inversa. El descenso de la Tb.Sp en el hueso injertado de los dos grupos puede explicarse por el aumento sigificativo del grosor trabecular en el grupo t2 y por el aumento del número trabecular en el grupo t1, comparándolos con el hueso nativo respectivamente. No se encontró ninguna diferencia estadísticamente significativa entre los dos grupos de hueso injertado cuando se compararon los parámetros morfométricos y de BMD. Conclusiones: Un injerto compuesto por 50% hueso autólogo y 50% biomaterial muestra que no hay diferencias en la microestructura 3D ni en la BMD entre 4-5 o 6-8 meses de espera de cicatrización ósea. Por ello este tiempo de cicatrización se puede acortar a 4 meses con la seguridad de un área injertada con hueso maduroPurpose: To evaluate the ideal implant time insertion in human bone biopsies after maxillary sinus floor elevation (MSFE) with a composite graft consisting of an equal amount of biomaterial and autologous bone, by comparing the bone regeneration obtained 4-5 months after surgery with the obtained after 6-8 months, and having the adjacent native bone as reference. Materials and Methods: A total of 26 biopsies of 11 patients after MSFE were analyzed. Two groups were created depending on the time of implant insertion: t1 group at 4-5 months (n=13) and t2 group at 6-8 months (n=13). The same volume of grafted bone and native bone were analyzed for each biopsy by micro-computed tomography (microCT). Results: Statistically significant differences were found in bone mineral density, bone volume fraction and trabecular separation (Tb. Sp) between native and grafted bone in the t1 and t2 groups, showing grafted bone higher values except for the variable Tb.Sp, which were lower in the grafted bone compared to native bone. The decrease in Tb.Sp in the grafted bone for t1 and t2 groups can be explained by the significant increase in trabecular thickness in t2 group and the trabecular number in t1 group, compared to native bone respectively. Comparing the morphometric parameters and the BMD of the grafted bone between the t1 and t2 groups, no significant differences were found. Conclusions: A composite graft composed of 50% autologous bone and 50% biomaterial shows no differences in 3D microstructure and BMD between 4-5 months and 6-8 months of healing time. Thus, this time can be shortened to 4 months with the security of a grafted area of mature bone

Interleukin-10 facilitates the selection of patients for systemic thrombolysis

Background: Clinical-Diffusion mismatch (CDM; NIHSS score ≥8 & DWI lesion volume ≤25 mL) and Perfusion-Diffusion mismatch (PDM; difference >20% between initial DWI and MTT lesion volumes) have been proposed as surrogates for ischemic brains that are at risk of infarction. However, their utility to improve the selection of patients for thrombolytic treatment remains controversial. Our aim was to identify molecular biomarkers that can be used with neuroimaging to facilitate the selection of ischemic stroke patients for systemic thrombolysis. Methods: We prospectively studied 595 patients with ischemic stroke within 12 h of the stroke onset. A total of 184 patients received thrombolytic treatment according to the SITS-MOST criteria. DWI and MTT volumes were measured at admission. The main outcome variable was good functional outcome at 3 months (modified Rankin scale <3). Serum levels of glutamate (Glu), IL-10, TNF-α, IL-6, NSE, and active MMP-9 also were determined at admission. Results: Patients treated with t-PA who presented with PDM had higher IL-10 levels at admission (p < 0.0001). In contrast, patients with CDM had higher levels of IL-10 (p < 0.0001) as well as Glu and TNF-α (all p < 0.05) and lower levels of NSE and active MMP-9 (all p < 0.0001). IL-10 ≥ 30 pg/mL predicts good functional outcome at 3 months with a specificity of 88% and a sensitibity of 86%. IL-10 levels ≥30 pg/mL independently in both patients with PDM (OR, 18.9) and CDM (OR, 7.5), after an adjustment for covariates. Conclusions: Serum levels of IL-10 facilitate the selection of ischemic stroke patients with CDM and PDM for systemic thrombolysis

In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia

The use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier. Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in developed countries. We first performed a series of proteomic, immunoblotting and immunohistological studies to characterize the expression of molecular biomarkers for the so-called peri-infarct tissue, a key region of the brain for stroke treatment. We confirmed that the HSP72 protein is a suitable biomarker for the peri-infarct region, as it is selectively expressed by at-risk tissue for up to 7 days following cerebral ischemia. We also describe the development of anti-HSP72 vectorized stealth immunoliposomes containing imaging probes to make them traceable by conventional imaging techniques (fluorescence and MRI) that were used to encapsulate a therapeutic agent (citicoline) for the treatment of cerebral ischemia. We tested the molecular recognition capabilities of these nano-platforms in vitro together with their diagnostic and therapeutic properties in vivo, in an animal model of cerebral ischemia. Using MRI, we found that 80% of vectorized liposomes were located on the periphery of the ischemic lesion, and animals treated with citicoline encapsulated on these liposomes presented lesion volumes up to 30% smaller than animals treated with free (non-encapsulated) drugs. Our results show the potential of nanotechnology for the development of effective tools for the treatment of neurological diseases

Glutamate Excitoxicity Is the Key Molecular Mechanism Which Is Influenced by Body Temperature during the Acute Phase of Brain Stroke

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke

Human recombinant glutamate oxaloacetate transaminase 1 (GOT1) supplemented with oxaloacetate induces a protective effect after cerebral ischemia

Blood glutamate scavenging is a novel and attractive protecting strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. Glutamate oxaloacetate transaminase 1 (GOT1) activation by means of oxaloacetate administration has been used to reduce the glutamate concentration in the blood. However, the protective effect of the administration of the recombinant GOT1 (rGOT1) enzyme has not been yet addressed in cerebral ischemia. The aim of this study was to analyze the protective effect of an effective dose of oxaloacetate and the human rGOT1 alone and in combination with a non-effective dose of oxaloacetate in an animal model of ischemic stroke. Sixty rats were subjected to a transient middle cerebral artery occlusion (MCAO). Infarct volumes were assessed by magnetic resonance imaging (MRI) before treatment administration, and 24 h and 7 days after MCAO. Brain glutamate levels were determined by in vivo MR spectroscopy (MRS) during artery occlusion (80 min) and reperfusion (180 min). GOT activity and serum glutamate concentration were analyzed during the occlusion and reperfusion period. Somatosensory test was performed at baseline and 7 days after MCAO. The three treatments tested induced a reduction in serum and brain glutamate levels, resulting in a reduction in infarct volume and sensorimotor deficit. Protective effect of rGOT1 supplemented with oxaloacetate at 7 days persists even when treatment was delayed until at least 2 h after onset of ischemia. In conclusion, our findings indicate that the combination of human rGOT1 with low doses of oxaloacetate seems to be a successful approach for stroke treatment.Ministeiro de Economía y Competitividad de EspañaXunta de Galicia /Consellería Economía IndustriaXunta de Galicia/ Consellería EducaciónInstituto de Salud Carlos IIISpanish Research Network on Cerebrovascular Diseases RETICS-INVICTUSFundación Mútua MadrileñaEuropean Union program FEDEREspaña. Ministerio de Economía y Competitividad/SAF2011-30517Xunta de Galicia /Consellería Economía Industria/10PXIB918282PRXunta de Galicia / Consellería Educación/ CN2011/010Instituto de Salud Carlos III/PI11/00909Instituto de Salud Carlos III/CP12/03121Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS /RD12/0014Instituto de Salud Carlos III/PI10/00449Instituto de Salud Carlos III/PI12/0311

Cerebellar alterations in a model of Down syndrome: The role of the Dyrk1A gene

Down syndrome (DS) is characterized by a marked reduction in the size of the brain and cerebellum. These changes play an important role in the motor alterations and cognitive disabilities observed in this condition. The Ts65Dn (TS) mouse, the most commonly used model of DS, reflects many DS phenotypes, including alterations in cerebellar morphology. One of the genes that is overexpressed in both individuals with DS and TS mice is DYRK1A/Dyrk1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which has been implicated in the altered cerebellar structural and functional phenotypes observed in both populations. The aim of this study was to evaluate the effect of Dyrk1A on different alterations observed in the cerebellum of TS animals. TS mice were crossed with Dyrk1A +/- KO mice to obtain mice with a triplicate segment of Mmu16 that included Dyrk1A (TS +/+/+), mice with triplicate copies of the same genes that carried only two copies of Dyrk1A (TS +/+/-), euploid mice that expressed a normal dose of Dyrk1A (CO +/+) and CO animals with a single copy of Dyrk1A (CO +/-). Male mice were used for all experiments. The normalization of the Dyrk1A gene dosage did not rescue the reduced cerebellar volume. However, it increased the size of the granular and molecular layers, the densities of granular and Purkinje cells, and dendritic arborization. Furthermore, it improved the excitatory/inhibitory balance and walking pattern of TS +/+/- mice. These results support the hypothesis that Dyrk1A is involved in some of the structural and functional cerebellar phenotypes observed in the TS mouse model.This work was supported by grants from the Jerome Lejeune Foundation and Fundación Tatiana Pérez de Guzmán el Bueno and the Spanish Ministry of Economy and Competitiveness (PSI-2016-76194-R, AEI/FEDER, EU) and “Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0037)” from Spain