Solar-Simulated Ultraviolet Radiation Induces Abnormal Maturation and Defective Chemotaxis of Dendritic Cells

Exposure to ultraviolet (UV) light induces immunosuppression. Different evidences indicate that this phenomenon is mainly a consequence of the effect of UV light on skin dendritic cells (DC). To investigate the cellular and molecular basis of this type of immunosuppression, we assessed in vitro the effect of solar-simulated UV radiation on the phenotypic and functional characteristics of human monocyte-derived DC and Langerhans-like DC. UV radiation induced a decreased expression of molecules involved in antigen capture as DC-SIGN and the mannose receptor. This effect was accompanied by a diminished endocytic capacity, an enhanced expression of molecules involved in antigen presentation such as major histocompatibility complex-II and CD86, and a significant increase in their capability to stimulate T cells. Furthermore, irradiated DC failed to acquire a full mature phenotype upon treatment with lipopolysaccharide. On the other hand, solar-simulated radiation induced the secretion of tumor necrosis factor-αand interleukin (IL)-10 by DC, but no IL-12. Interestingly, solar-simulated UV radiation also caused an altered migratory phenotype, with an increased expression of CXCR4, and a lack of induction of CCR7, thus correlating with a high chemotactic response to stromal cell-derived factor 1(SDF-1) (CXCL12), but not to secondary lymphoid tissue chemokine (SLC) (CCL21). These data indicate that solar-simulated UV radiation induces a defective maturation and an anomalous migratory phenotype of DC

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

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

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

Impact of the COVID-19 pandemic on the organisation of stroke care. Madrid Stroke Care Plan

La sobrecarga asistencial y los cambios organizativos frente a la pandemia de COVID-19 podrían estar repercutiendo en la atención al ictus agudo en la Comunidad de Madrid. Métodos: Encuesta estructurada en bloques: características del hospital, cambios en infraestructura y recursos, circuitos de código ictus, pruebas diagnósticas, rehabilitación y atención ambulatoria. Análisis descriptivo según el nivel de complejidad en la atención del ictus (disponibilidad o no de unidad de ictus y de trombectomía mecánica). Resultados: De los 26 hospitales del SERMAS que atienden urgencias en adultos, 22 cumplimentaron la encuesta entre el 16 y 27 de abril. El 95% han cedido neurólogos para atender a pacientes afectados por la COVID-19. Se han reducido camas de neurología en el 89,4%, modificado los circuitos en urgencias para ictus en el 81%, con circuitos específicos para sospecha de infección por SARS-CoV2 en el 50%, y en el 42% de los hospitales los pacientes con ictus agudo positivos para SARS-CoV2 no ingresan en camas de neurología. Ha mejorado el acceso altratamiento, con trombectomía mecánica las 24 h en el propio hospital en 10 hospitales, y sehan reducido los traslados interhospitalarios secundarios. Se ha evitado el ingreso de pacientescon ataque isquémico transitorio o ictus leve (45%) y se han incorporado consultas telefónicaspara seguimiento en el 100%.Conclusiones: Los cambios organizativos de los hospitales de la Comunidad de Madrid frente ala pandemia por SARS-Co2 han modificado la dedicación de recursos humanos e infraestructurasde las unidades de neurología y los circuitos de atención del ictus, realización de pruebasdiagnósticas, ingreso de los pacientes y seguimientoThe overload of the healthcare system and the organisational changes made inresponse to the COVID-19 pandemic may be having an impact on acute stroke care in the Regionof Madrid.Methods: We conducted a survey with sections addressing hospital characteristics, changes ininfrastructure and resources, code stroke clinical pathways, diagnostic testing, rehabilitation,and outpatient care. We performed a descriptive analysis of results according to the level ofcomplexity of stroke care (availability of stroke units and mechanical thrombectomy).Results: The survey was completed by 22 of the 26 hospitals in the Madrid Regional HealthSystem that attend adult emergencies, between 16 and 27 April 2020. Ninety-five percent ofhospitals had reallocated neurologists to care for patients with COVID-19. The numbers of neuro-logy ward beds were reduced in 89.4% of hospitals; emergency department stroke care pathwayswere modified in 81%, with specific pathways for suspected SARS-CoV2 infection established in50% of hospitals; and SARS-CoV2-positive patients with acute stroke were not admitted to neu-rology wards in 42%. Twenty-four hour on-site availability of mechanical thrombectomy wasimproved in 10 hospitals, which resulted in a reduction in the number of secondary hospitaltransfers. The admission of patients with transient ischaemic attack or minor stroke was avoi-ded in 45% of hospitals, and follow-up through telephone consultations was implemented in100%.Conclusions: The organisational changes made in response to the SARS-Co2 pandemic in hos-pitals in the Region of Madrid have modified the allocation of neurology department staff andinfrastructure, stroke units and stroke care pathways, diagnostic testing, hospital admissions,and outpatient follow-u

Acute stroke care during the COVID-19 pandemic. Ictus Madrid Program recommendations

La pandemia por COVID-19 ha obligado a una reorganización de los sistemas sanitarios y ha comportado una saturación excepcional de sus recursos. En este contexto es vital asegurar la atención al ictus agudo y optimizar los procesos asistenciales del código ictus para reducir el riesgo de contagios y racionalizar el uso de recursos hospitalarios. Para ello, desde el Grupo Multidisciplinar Ictus Madrid proponemos una serie de recomendaciones. Métodos Revisión bibliográfica no sistemática de las publicaciones disponibles con los términos «stroke» y «COVID-19» o «coronavirus» o «SARS-CoV-2», así como otras conocidas por los autores. En base a esta se redacta un documento de recomendaciones que es sometido a consenso por el Grupo Multidisciplinar Ictus Madrid y su Comité de Neurología. Resultados Las recomendaciones se estructuran en cinco líneas fundamentales: 1) coordinar la actuación para garantizar el acceso a la asistencia hospitalaria de los pacientes con ictus; 2) reconocer a los pacientes con ictus potencialmente infectados por COVID-19, 3) organización adecuada para garantizar la protección de los profesionales sanitarios frente al riesgo de contagio por COVID-19, 4) en la realización de neuroimagen y otros procedimientos que conlleven contactos de riesgo de infección COVID-19 hay que procurar reducirlos y asegurar la protección, y 5) alta y seguimiento seguros procurando optimizar la ocupación hospitalaria. Resumimos el procedimiento de forma esquemática con el acrónimo CORONA (COordinar, Reconocer, Organizar, Neuroimagen, Alta). Conclusiones Estas recomendaciones pueden servir de apoyo para la organización del sistema sanitario en la atención al ictus agudo y la optimización de sus recursos, garantizando la protección de sus profesionalesThe COVID-19 pandemic has forced a reorganization of healthcare systems and an exceptional saturation of their resources. In this context, it is vital to ensure acute stroke care and optimize the care processes of the stroke code to reduce the risk of contagion and rationalize the use of hospital resources. To do this, the Ictus Madrid Multidisciplinary Group proposes a series of recommendations. Methods Non-systematic bibliographic review of the available publications with the terms «stroke» and «COVID-19» or «coronavirus» or «SARS-CoV-2», as well as other already known for the authors. We provide a document of recommendations as a result of the consensus of the Ictus Madrid Multidisciplinary Group and its Neurology Committee. Results Our recommendations are structured on five lines: (1) coordinate to guarantee the access to hospital care for stroke patients, (2) recognize potentially COVID-19 infected stroke patients, (3) organize to ensure the protection of healthcare professionals from COVID-19 infections, (4) neuroimaging and other procedures potentially associated to risks for COVID-19 infection should be reduced and secured to avoid contagion, and (5) at home as soon as possible and supported follow-up to optimize hospital occupancy. The procedure is shown summarized under the acronym CORONA (COordinate, Recognize, Organize, Neuroimaging, At home). Conclusions These recommendations can support the organization of healthcare services for acute stroke care and the optimization of their resources, guaranteeing the protection of healthcare professional

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes