Predictive Value of Serum Antibodies and Point Mutations of AQP4, AQP1 and MOG in A Cohort of Spanish Patients with Neuromyelitis Optica Spectrum Disorders

The detection of IgG aquaporin-4 antibodies in the serum of patients with Neuromyelitis optica (NMO) has dramatically improved the diagnosis of this disease and its distinction from multiple sclerosis. Recently, a group of patients have been described who have an NMO spectrum disorder (NMOsd) and who are seronegative for AQP4 antibodies but positive for IgG aquaporin-1 (AQP1) or myelin oligodendrocyte glycoprotein (MOG) antibodies. The purpose of this study was to determine whether AQP1 and MOG could be considered new biomarkers of this disease; and if point mutations in the gDNA of AQP4, AQP1 and MOG genes could be associated with the etiology of NMOsd. We evaluated the diagnostic capability of ELISA and cell-based assays (CBA), and analyzed their reliability, specificity, and sensitivity in detecting antibodies against these three proteins. The results showed that both assays can recognize these antigen proteins under appropriate conditions, but only anti-AQP4 antibodies, and not AQP1 or MOG, appears to be a clear biomarker for NMOsd. CBA is the best method for detecting these antibodies; and serum levels of AQP4 antibodies do not correlate with the progression of this disease. So far, the sequencing analysis has not revealed a genetic basis for the etiology of NMOsd, but a more extensive analysis is required before definitive conclusions can be drawn.Ministerio de Economía y CompetitividadFEDER (Grants PI16/01249 y PI16/00493

The chemical basis of thiol addition to nitro-conjugated linoleic acid, a protective cell-signaling lipid

Nitroalkene fatty acids are formed in vivo and exert protective and anti-inflammatory effects via reversible Michael addition to thiol-containing proteins in key signaling pathways. Nitro-conjugated linoleic acid (NO2-CLA) is preferentially formed, constitutes the most abundant nitrated fatty acid in humans, and contains two carbons that could potentially react with thiols, modulating signaling actions and levels. In this work, we examined the reactions of NO2-CLA with low molecular weight thiols (glutathione, cysteine, homocysteine, cysteinylglycine, and β-mercaptoethanol) and human serum albumin. Reactions followed reversible biphasic kinetics, consistent with the presence of two electrophilic centers in NO2-CLA located on the β- and δ-carbons with respect to the nitro group. The differential reactivity was confirmed by computational modeling of the electronic structure. The rates (kon and koff) and equilibrium constants for both reactions were determined for different thiols. LC-UV-Visible and LC-MS analyses showed that the fast reaction corresponds to β-adduct formation (the kinetic product), while the slow reaction corresponds to the formation of the δ-adduct (the thermodynamic product). The pH dependence of the rate constants, the correlation between intrinsic reactivity and thiol pKa, and the absence of deuterium solvent kinetic isotope effects suggested stepwise mechanisms with thiolate attack on NO2-CLA as rate-controlling step. Computational modeling supported the mechanism and revealed additional features of the transition states, anionic intermediates, and final neutral products. Importantly, the detection of cysteine-δ-adducts in human urine provided evidence for the biological relevance of this reaction. Finally, human serum albumin was found to bind NO2-CLA both non-covalently and to form covalent adducts at Cys-34, suggesting potential modes for systemic distribution. These results provide new insights into the chemical basis of NO2-CLA signaling actions

Mediterranean Diet and its Effects on Silent Brain Infarcts in a Cohort of Patients With Atrial Fibrillation

[Background and Aims] The benefits of Mediterranean Diet (MeDiet) in prevention of cardiovascular diseases (CVD) in general and ischemic stroke (IS) have been extensively studied and reported. We hypothesize that the consumption of nutrients typical of MeDiet would also reduce the rate of silent brain infarcts (SBI) among AF patients.[Methods and Results] Patients with a history of AF who scored 0 to 1 in the CHADS2 score, ⩾50 years and with absence of neurological symptoms were selected from Seville urban area using the Andalusian electronic healthcare database. A 3T brain MRI was performed to all participants. Demographic and clinical data and food-frequency questionnaire (FFQ) were collected. Of the 443 scanned patients, 66 presented SBI. Of them 52 accepted to be scheduled for a clinical visit and were included in the diet sub study and 41 controls were matched per age and sex. There were no statistically significant differences in baseline characteristics. After logistic regression analysis, we found that a higher consumption of fiber from fruit was independently associated with a lower risk of SBI, while a higher consumption of high glycemic load (GL) foods was associated with a higher risk of SBI in a population with AF[Conclusion] Our findings support that MeDiet could be suggested as a prevention strategy for SBI in patients with AF.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Spanish Ministry of Economy, Industry and Competitiveness (grant RTC-2016 5300-1), the Junta de Andalucía (grant PIN-0144-2016) and Neuroprotección Avanzada Reposicionando Drogas y Nutraceúticos para el Ictus en Andalucía: Proyecto NARDNIA (PE-0527-2019), the European Project ITRIBIS (registration number REGPOT-2013-1), and Cooperative Cerebrovascular Disease Research Network (INVICTUS+, RD16/0019/0015) supported the study. The Fundación Cajasol also contributed to the study.Peer reviewe

Guía Aqua-Riba

La guía que se presenta es el resultado principal del proyecto "Aqua-Riba: Sistemas de Gestión Sostenible del Ciclo Urbano del Agua en la Rehabilitación Integral de Barriadas en Andalucía". El documento pretende ser una herramienta conceptual, metodológica y operativa para la construcción de "ciudades sensibles al agua". La guía proporcona instrumentos para materializar el enfoque socio-ecológico de gestión del ciclo urbano del agua en los proyectos de rehabilitación arquitectónica y urbana. Los destinatarios de esta guía son los responsables y agentes activos de los procesos de intervención urbana, así como los agentes sociales (asociaciones y comunidades de vecinos y otros colectivos sociales). La guía incluye 6 apartados. Uno incial de presentación, al que sigue le segundo dedicado a exponer la situación de la gestión del ciclo urbano del agua en Andalucía y los principios en lo que se asienta el modelo alternativo de gestión propuesto. En tercer lugar se presenta una propuesta metodológica participativa para la gestión eco-integradora del ciclo del agua en los proyectos de intervención urbana. En el capitulo 5 se exponen las diversa estrategias de intervención, referidas al abastecimiento, las relaciones agua-energía, las aguas pluviales y las aguas residuales. La guía se acompaña de un extenso apartado de 6 anexos: fuentes de información; marco institucional y recursos para el diseño de proyectos; y un repertorio de 85 fichas tecnológicas en las que se sintetiza un importante volumen de información, homogéneamente estructurada y sistematizada. Cierra estos anexos la presentación detallada de la propuesta metodológica aplicada al caso de estudio del Barrio de Las Huertas (Sevilla)

Intravenous Thrombolysis Guided by Perfusion CT with Alteplase in >4.5 Hours from Stroke Onset

[Introduction]: The benefit of intravenous thrombolysis (IVT) in wake-up stroke (WUS), stroke of unknown time of onset (SUKO), or when time exceeds 4.5 h from last-seen-normal (LSN) guided by CT perfusion (CTP) or MRI has been recently suggested. However, there is limited information of IVT in those patients in real-world studies. Objective: Our aim was to evaluate safety and efficacy of IVT selected by CTP in patients with WUS, SUKO, or stroke of time onset beyond 4.5 h. [Material and Methods]: We studied a prospective cohort of patients who underwent IVT from January 2010 to December 2017. Two groups were defined: standard of care group (SC) included patients with time onset 4.5 h from LSN with penumbra area in CTP. We evaluated baseline characteristics, functional outcomes according to modified Rankin Scale (mRS) at discharge and at 90 days, and intracranial hemorrhages rates. [Results]: 657 patients were studied: 604 (92%) were treated in the SC group and 53 (8%) in the CTP group. The mean NIHSS score was 9.8 in the CTP group versus 13 in the SC group (p = 0.001). Seventeen patients in the CTP group (32.1%) received bridging therapy with mechanical thrombectomy (MT). Last time seen well-to-needle time was 538 versus 155 min (p < 0.001). The incidence of symptomatic intracranial hemorrhage was equal in both groups (3.8 vs. 3.8%, p = 1). Good functional outcome (mRS < 2) was achieved in both groups (72 vs. 60.4%, p = 0.107). [Conclusions]: IVT in patients with WUS, SUKO, or stroke beyond >4.5 h from LSN, with salvageable brain tissue on CTP, seems to be safe and has similar functional outcomes at 90 days to the standard therapeutic window, even when combined with MT

Clinical Outcomes of Mechanical Thrombectomy in Stroke Tandem Lesions According to Intracranial Occlusion Location

This project was partially funded by the ISCIII project PI14/00971. The ITRIBiS project (Improving Translational Research Potential at the Institute of Biomedicine of Seville) has the registration number REGPOT-2013-1. Cooperative Cerebrovascular Disease Research Network (INVICTUS+) (RD16/0019/0015).Ye

Prevalence and risk factors of silent brain infarcts in patients with AF detected by 3T-MRI

[Background] Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause of SBI.[Objectives] The aim of this study is to determine the prevalence of and risk factors for SBI in patients with AF and low-to-moderate embolic risk according to CHADS2 and CHA2DS2VASc score.[Methods] Patients with a history of AF based on medical records who scored 0–1 in the CHADS2 score were selected from the Seville urban area using the Andalusian electronic healthcare database (DIRAYA). Demographic and clinical data were collected and a 3T brain MRI was performed on patients older than 50 years and with absence of neurological symptoms.[Results] 66 of the initial 443 patients (14.9%) and 41 of the 349 patients with low risk according to CHA2DS2VASc score (11.7%) presented at least 1 SBI. After adjusted multivariable analysis, an older age (OR 3.84, 95% CI 1.07–13.76) and left atrial (LA) enlargement (OR 3.13, 95% CI 1.15–8.55) were associated with SBI in the whole cohort, while only LA enlargement was associated with SBI in the low-risk cohort (OR 3.19, 95% CI 1.33–7.63).[Conclusions] LA enlargement on echocardiogram was associated with SBI in patients with AF and low or moderate embolic risk according to CHADS2 and in the low-risk population according to CHA2DS2VASc. Although further studies are needed, a neuroimaging screening might be justified in these patients to guide medical therapies to improve stroke prevention.The Spanish Ministry of Economy, Industry and Competitiveness (Grant RTC-2016-5300-1), the Junta de Andalucía (Grant PIN-0144-2016) and the European Project ITRIBIS supported the study. The Fundación Cajasol also contributed to the study. Neurovascular Research Group is part of the Spanish Neurovascular Disease Research Network (INVICTUS + , RD16/0019/0015)

Mediterranean Diet and Physical Activity Protect from Silent Brain Infarcts in a Cohort of Patients with Atrial Fibrillation.

Several studies have demonstrated that Mediterranean diet (MeD) has beneficial effects in the prevention of cardiovascular disease (CVD)1,2 globally but also in stroke prevention.3,4 However, there are few data of the influence of MeD in silent brain infarcts (SBI). Physical activity is also a well-known protective factor for CVD and stroke.5 Atrial fibrillation (AF) increases the risk of overt stroke and also SBI. We hypothesize that a healthy lifestyle would reduce the rate of SBI among AF patients. The aim of this study is to determine the association of a healthy profile (the combination of a good MeD adherence plus high level of physical activity) and the prevalence of SBI in a population with AF

Circulating microRNA after autologous bone marrow mononuclear cell (BM-MNC) injection in patients with ischemic stroke

Previous studies have shown the potential of microRNAs (miRNA) in the pathological process of stroke and functional recovery. Bone marrow mononuclear cell (BM-MNC) transplantation improves recovery in experimental models of ischemic stroke that might be related with miRNA modifications. However, its effect on circulating miRNA has not been described in patients with stroke. We aimed to evaluate the circulating levels of miRNAs after autologous BM-MNC transplantation in patients with stroke. We investigate the pattern of miRNA-133b and miRNA-34a expression in patients with ischemic stroke included in a multicenter randomized controlled phase IIb trial (http://www.clinicaltrials.gov; unique identifier: NCT02178657). Patients were randomized to 2 different doses of autologous intra-arterial BM-MNC injection (2×106/kg or 5×106/kg) or control group within the first 7 days after stroke onset. We evaluate plasma concentration of miRNA-113b and miRNA-34a at inclusion and 4, 7, and 90 days after treatment. Thirteen cases (8 with 2×106/kg BM-MNC dose and 5 with 5×106/kg dose) and 11 controls (BM-MNC non-treated) were consecutively included. Mean age was 64.1±12.3 with a mean National Institutes of Health Stroke Scale score at inclusion of 14.5. Basal levels of miRNA were similar in both groups. miR-34a-5p and miR-133b showed different expression patterns. There was a significant dose-dependent increase of miRNA-34a levels 4 days after BM-MNC injection (fold change 3.7, p<0.001), whereas miRNA-133b showed a significant increase in the low-dose BM-MNC group at 90 days. Intra-arterial BM-MNC transplantation in patients with ischemic stroke seems to modulate early circulating miRNA-34a levels, which have been related to precursor cell migration in stroke and smaller infarct volumes.This work has been supported by the grants PI15/01197, PI18/01414 and RD16/0019/0015 (INVICTUS+) from the Spanish Ministry of Economy and Competitiveness, cofunded by ISCIII and FEDER funds; Mutua Madrileña grant. FMa is supported by a Rio Hortega contract (CM16/00015). Andalusian Initiative for Advanced Therapies (IATA) is the sponsor of the trial