Alberta Stroke Program Early CT Score applied to CT angiography source images is a strong predictor of futile recanalization in acute ischemic stroke

The final publication is available at Springer via http://dx.doi.org/10.1007/s00234-016-1652-7Introduction Reliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization. Methods Data are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, timelapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24 h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90 days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability). Results Included were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45 %), primary mechanical thrombectomy (MT; 16 %), or combined IVT+MT (39 %). Recanalization rate was 71 %, median delay of 287 min (225; 357). Recanalization was futile in 28 % of cases. In an adjusted model, baseline CTA-SI-ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95 % CI 0.3–0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95 % CI 0.5–1.2). A score ≤5 in CTA-SIASPECTS was the best cut-off to predict futile recanalization (sensitivity 35 %; specificity 97 %; positive predictive value 86 %; negative predictive value 77 %). Conclusions CTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapie

International consensus on (ICON) anaphylaxis

ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public

Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations

Oncostatin M-Enriched Small Extracellular Vesicles Derived from Mesenchymal Stem Cells Prevent Isoproterenol-Induced Fibrosis and Enhance Angiogenesis

Myocardial fibrosis is a pathological hallmark of cardiac dysfunction. Oncostatin M (OSM) is a pleiotropic cytokine that can promote fibrosis in different organs after sustained exposure. However, OSM released by macrophages during cardiac fibrosis suppresses cardiac fibroblast activation by modulating transforming growth factor beta 1 (TGF-1) expression and extracellular matrix Citation: Tejedor, S.; Buigues, M.; González-King, H.; Silva, A.M.; García, N.A.; Dekker, N.; Sepúlveda, P. Oncostatin M-Enriched Small Extracellular Vesicles Derived from Mesenchymal Stem Cells Prevent Isoproterenol-Induced Fibrosis and Enhance Angiogenesis. Int. J. Mol. Sci. 2023, 24, 6467. https://doi.org/ 10.3390/ijms24076467 Academic Editors: Eltyeb Abdelwahid andKatherine Athayde Teixeira de Carvalho Received: 18 March 2023 Revised: 21 March 2023 Accepted: 26 March 2023 Published: 30 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). deposition. Small extracellular vesicles (SEVs) from mesenchymal stromal cells (MSCs) are being investigated to treat myocardial infarction, using different strategies to bolster their therapeutic ability. Here, we generated TERT-immortalized human MSC cell lines (MSC-T) engineered to overexpress two forms of cleavage-resistant OSM fused to CD81TM (OSM-SEVs), which allows the display of the cytokine at the surface of secreted SEVs. The therapeutic potential of OSM-SEVs was assessed in vitro using human cardiac ventricular fibroblasts (HCF-Vs) activated by TGF-1. Compared with control SEVs, OSM-loaded SEVsreducedproliferation in HCF-V andblunted telo-collagen expression. When injected intraperitoneally into mice treated with isoproterenol, OSM-loaded SEVs reduced f ibrosis, prevented cardiac hypertrophy, and increased angiogenesis. Overall, we demonstrate that the enrichment of functional OSM on the surface of MSC-T-SEVs increases their potency in terms of anti-fibrotic and pro-angiogenic properties, which opens new perspectives for this novel biological product in cell-free-based therapies

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Staphylococci among Wild European Rabbits from the Azores: A Potential Zoonotic Issue?

Artículo Open Access[EN]. The prevalence and diversity of Staphylococcus species from wild European rabbits (Oryctolagus cuniculus) in the Azores were investigated, and the antibiotic resistance phenotype and genotype of the isolates were determined. Nasal samples from 77 wild European rabbits from São Jorge and São Miguel islands in Azores were examined. Antibiotic susceptibility of the isolates was determined using the Kirby-Bauer disk diffusion method, and the presence of antimicrobial resistance genes and virulence factors was determined by PCR. The genetic lineages of S. aureus isolates were characterized by spa typing and multilocus sequence typing. A total of 49 staphylococci were obtained from 35 of the 77 wild rabbits. Both coagulase-positive (8.2%) and coagulase-negative (91.8%) staphylococci were detected: 4 S. aureus, 17 S. fleurettii, 13 S. sciuri, 7 S. xylosus, 4 S. epidermidis, and 1 each of S. simulans, S. saprophyticus, S. succinus, and S. equorum. The four S. aureus isolates showed methicillin susceptibility and were characterized as spa type t272/CC121, Panton-Valentine leukocidin negative, and hlB positive. Most of the coagulase-negative staphylococci showed resistance to fusidic acid and beta-lactams, and multidrug resistance was identified especially among S. epidermidis isolates. The mecA gene was detected in 20 isolates of the species S. fleurettii and S. epidermidis, associated with the blaZ gene in one S. epidermidis isolate. Five antimicrobial resistance genes were detected in one S. epidermidis isolate (mecA, dfrA, dfrG, aac60-aph20 0, and ant4). Our results highlight that wild rabbits are reservoirs or “temporary hosts” of Staphylococcus species with zoonotic potential, some of them carrying relevant antimicrobial resistancesSIThis work was funded by the R&D Project CAREBIO2— Comparative assessment of antimicrobial resistance in environmental biofilms through proteomics—towards innovative theranostic biomarkers, with reference NORTE-01-0145-FEDER-030101 and PTDC/SAU-INF/ 30101/2017, financed by the European Regional Development Fund (ERDF) through the Northern Regional Operational Program (NORTE 2020) and the Foundation for Science and Technology (FCT). This research was supported by funding from the Research Group SEGURALI. Margarida Sousa and Vanessa Silva have their Ph.D. fellowships granted by FCT (Fundação para a Ciência e a Tecnologia, Portugal) with the references SFRH/BD/87302/2012 and SFRH/BD/137947/2018, respectively. Nuno Silva was supported by “Programa Ciência 2008” cofinanced by POPH/QREN Type 4.2: Employment Promotion Scientific subsidized by the European Social Fund and National Funds of the Ministry of Science and Technology for Higher Education (MCTES)

Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial

Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] 8–20) were randomized (1:1) to receive intravenous adipose tissue–derived mesenchymal stem cells (AD-MSCs) or placebo within the first 2 weeks of stroke onset. The primary outcome was safety, evaluating adverse events (AEs), neurologic and systemic complications, and tumor development. The secondary outcome evaluated treatment efficacy by measuring modified Rankin Scale (mRS), NIHSS, infarct size, and blood biomarkers. We report the final trial results after 24 months of follow-up. Recruitment began in December 2014 and stopped in December 2017 after 19 of 20 planned patients were included. Six patients did not receive study treatment: two due to technical issues and four for acquiring exclusion criteria after randomization. The final study sample was composed of 13 patients (4 receiving AD-MSCs and 9 placebo). One patient in the placebo group died within the first week after study treatment delivery due to sepsis. Two non-treatment-related serious AEs occurred in the AD-MSC group and nine in the placebo group. The total number of AEs and systemic or neurologic complications was similar between the study groups. No injection-related AEs were registered, nor tumor development. At 24 months of follow-up, patients in the AD-MSC group showed a nonsignificantly lower median NIHSS score (interquartile range, 3 [3–5.5] vs 7 [0–8]). Neither treatment group had differences in mRS scores throughout follow-up visits up to month 24. Therefore, intravenous treatment with AD-MSCs within the first 2 weeks from ischemic stroke was safe at 24 months of follow-u

Deepint.net: A rapid deployment platform for smart territories

This paper presents an efficient cyberphysical platform for the smart management of smart territories. It is efficient because it facilitates the implementation of data acquisition and data management methods, as well as data representation and dashboard configuration. The platform allows for the use of any type of data source, ranging from the measurements of a multi-functional IoT sensing devices to relational and non-relational databases. It is also smart because it incorporates a complete artificial intelligence suit for data analysis; it includes techniques for data classification, clustering, forecasting, optimization, visualization, etc. It is also compatible with the edge computing concept, allowing for the distribution of intelligence and the use of intelligent sensors. The concept of smart cities is evolving and adapting to new applications; the trend to create intelligent neighbourhoods, districts or territories is becoming increasingly popular, as opposed to the previous approach of managing an entire megacity. In this paper, the platform is presented, and its architecture and functionalities are described. Moreover, its operation has been validated in a case study where the bike renting service of Paris—Vélib’ Métropole has been managed. This platform could enable smart territories to develop adapted knowledge management systems, adapt them to new requirements and to use multiple types of data, and execute efficient computational and artificial intelligence algorithms. The platform optimizes the decisions taken by human experts through explainable artificial intelligence models that obtain data from IoT sensors, databases, the Internet, etc. The global intelligence of the platform could potentially coordinate its decision-making processes with intelligent nodes installed in the edge, which would use the most advanced data processing techniques.This work has been partially supported by the European Regional Development Fund (ERDF) through the Interreg Spain-Portugal V-A Program (POCTEP) under grant 0677_DISRUPTIVE_2_E, the project My-TRAC: My TRAvel Companion (H2020-S2RJU-2017), the project LAPASSION, CITIES (CYTED 518RT0558) and the company DCSC. Pablo Chamoso’s research work has been funded through the Santander Iberoamerican Research Grants, call 2020/2021, under the direction of Paulo Novais

Más allá de la hiperglucemia: la variabilidad glucémica como factor pronóstico en el infarto cerebral agudo

Glycaemic variability (GV) refers to variations in blood glucose levels, and may affect stroke outcomes. This study aims to assess the effect of GV on acute ischaemic stroke progression. We performed an exploratory analysis of the multicentre, prospective, observational GLIAS-II study. Capillary glucose levels were measured every 4 hours during the first 48 hours after stroke, and GV was defined as the standard deviation of the mean glucose values. The primary outcomes were mortality and death or dependency at 3 months. Secondary outcomes were in-hospital complications, stroke recurrence, and the impact of the route of insulin administration on GV. Results: A total of 213 patients were included. Higher GV values were observed in patients who died (n = 16; 7.8%; 30.9 mg/dL vs 23.3 mg/dL; p = 0.05). In a logistic regression analysis adjusted for age and comorbidity, both GV (OR = 1.03; 95% CI, 1.003-1.06; p = 0.03) and stroke severity (OR = 1.12; 95% CI, 1.04-1.2; p = 0.004) were independently associated with mortality at 3 months. No association was found between GV and the other outcomes. Patients receiving subcutaneous insulin showed higher GV than those treated with intravenous insulin (38.95 mg/dL vs 21.34 mg/dL; p < 0.001). Conclusions: High GV values during the first 48 hours after ischaemic stroke were independently associated with mortality. Subcutaneous insulin may be associated with higher VG levels than intravenous administration.La variabilidad glucémica (VG) hace referencia a las oscilaciones en los niveles de glucosa en sangre y podría influir en el pronóstico del ictus. Analizar el efecto de la VG en la evolución del infarto cerebral agudo (IC). Análisis exploratorio del estudio GLIAS-II (multicéntrico, prospectivo y observacional). Se midieron los niveles de glucemia capilar cada cuatro horas durante las primeras 48 horas y la VG se definió como la desviación estándar de los valores medios. Variables principales: mortalidad y muerte o dependencia a los tres meses. Variables secundarias: porcentaje de complicaciones intrahospitalarias y de recurrencia de ictus, e influencia de la vía de administración de insulina sobre la VG. Se incluyeron 213 pacientes. Los pacientes que fallecieron (N = 16;7,8%) presentaron mayores valores de VG (30,9 mg/dL vs. 23,3 mg/dL; p = 0,05). En el análisis de regresión logística ajustado por edad y comorbilidad, tanto la VG (OR = 1,03; IC del 95%: 1,003-1,06: p = 0,03) como la gravedad del IC (OR = 1,12; IC del 95%: 1,04-1,2; p = 0,004) se asociaron de forma independiente con la mortalidad a los tres meses. No se encontró asociación entre la VG y las demás variables de estudio. Los pacientes que recibieron tratamiento con insulina subcutánea mostraron una mayor VG que los tratados con insulina intravenosa (38,9 mg/dL vs. 21,3 mg/dL; p < 0,001). Conclusiones: Valores elevados de VG durante las primeras 48 horas tras el IC se asociaron de forma independiente con la mortalidad. La administración subcutánea de insulina podría condicionar una mayor VG que la vía intravenosaFinanciado por el Instituto de Salud Carlos III (ISCIII) y el FEDER (PI 09/01781). Promovido por el Proyecto Ictus del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Espanola ˜ de Neurología, y las Redes de Investigación temática RETICS INVICTUS e INVICTUS Plus (RD12/0014/0006, RD16/0019/0005

Epigenetic downregulation of TET3 reduces genome-wide 5hmC levels and promotes glioblastoma tumorigenesis

This work has been financially supported by the Plan Nacional de I+D+I 2013-2016/FEDER (PI15/00892 to M.F.F. and A.F.F.), the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (Miguel Servet contract CP11/00131 to A.F.F.); the Asturias Regional Government (GRUPIN14-052 to M.F.F.); FICYT (A.C. and M.G.); the Ministry of Economy and Competitiveness of Spain (J.R.T., Juan de la Cierva fellowship FJCI-2015-26965, V.L., Juan de la Cierva fellowship IJCI-2015-23316); Fundación Científica de la AECC (to R.G.U.); FINBA-ISPA (R.F.P.); IUOPA (G.F.B. and C.M.) and Fundación Ramón Areces (M.F.F.). A.F.F. is also financially supported by the Ministry of Economy and Competitiveness of Spain, the European Regional Development Fund (FEDER) and the Programa Retos de la Sociedad (RTC-2015-3393-1). The IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain