Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6 months

Erenumab; Migranya; Anticossos monoclonalsErenumab; Migraña; Anticuerpos monoclonicosErenumab; Migraine; Monoclonal antibodiesBackground In daily practice, anti-CGRP monoclonal antibodies (MAbs) may be useful in chronic migraine (CM) with medication overuse (MO), but data is limited. We evaluated their effectiveness in a real-life clinical cohort. Methods This is a prospective study conducted in CM patients with and without medication overuse treated with monthly MAbs during 6 months (erenumab/galcanezumab). We collected headache characteristics, including acute medication intake, through an electronic diary. We compared patients (1) with and without MO at baseline, (2) with and without ongoing MO after treatment, defining MO resolution as < 10 or 15 days/month of acute medication intake, according to analgesic type, during the 6-month treatment. Results Of 139 CM patients completing 6-month treatment with anti-CGRP MAbs, 71.2% (99/139) had MO at baseline. After 6 months, patients with and without MO at baseline had significant and similar proportions of ≥50% reduction in migraine days/month (MO: 63.6% vs. non-MO: 57.5%, p = 0.500). 60.6% (60/99) no longer satisfied MO definition. Reduction in headache frequency compared to baseline occurred in both MO-ongoing and MO-resolution group, although those who stopped overusing had a greater improvement (headache days/month: − 13.4 ± 7.6 vs. -7.8 ± 7.2, p < 0.0001). No differences in MO resolution were observed according to the MAbs used. Baseline lower pain severity was associated with MO resolution (OR [95%]:0.236[0.054–0.975]; p = 0.049). Conclusions In real-life anti-CGRP MAbs are as effective in CM patients with MO as in patients without it and facilitate MO cessation. Reduction in headache frequency and acute medication days/month occurs regardless of whether patients stop overusing or not.No funding was received for this study

A study of differential microRNA expression profile in migraine: the microMIG exploratory study

Epigenetics; Migraine; MicroRNAEpigenética; Migraña; MicroARNEpigenètica; Migranya; MicroARNBackground Several studies have described potential microRNA (miRNA) biomarkers associated with migraine, but studies are scarcely reproducible primarily due to the heterogeneous variability of participants. Increasing evidence shows that disease-related intrinsic factors together with lifestyle (environmental factors), influence epigenetic mechanisms and in turn, diseases. Hence, the main objective of this exploratory study was to find differentially expressed miRNAs (DE miRNA) in peripheral blood mononuclear cells (PBMC) of patients with migraine compared to healthy controls in a well-controlled homogeneous cohort of non-menopausal women. Methods Patients diagnosed with migraine according to the International Classification of Headache Disorders (ICHD-3) and healthy controls without familial history of headache disorders were recruited. All participants completed a very thorough questionnaire and structured-interview in order to control for environmental factors. RNA was extracted from PBMC and a microarray system (GeneChip miRNA 4.1 Array chip, Affymetrix) was used to determine the miRNA profiles between study groups. Principal components analysis and hierarchical clustering analysis were performed to study samples distribution and random forest (RF) algorithms were computed for the classification task. To evaluate the stability of the results and the prediction error rate, a bootstrap (.632 + rule) was run through all the procedure. Finally, a functional enrichment analysis of selected targets was computed through protein–protein interaction networks. Results After RF classification, three DE miRNA distinguished study groups in a very homogeneous female cohort, controlled by factors such as demographics (age and BMI), life-habits (physical activity, caffeine and alcohol consumptions), comorbidities and clinical features associated to the disease: miR-342-3p, miR-532-3p and miR-758-5p. Sixty-eight target genes were predicted which were linked mainly to enriched ion channels and signaling pathways, neurotransmitter and hormone homeostasis, infectious diseases and circadian entrainment. Conclusions A 3-miRNA (miR-342-3p, miR-532-3p and miR-758-5p) novel signature has been found differentially expressed between controls and patients with migraine. Enrichment analysis showed that these pathways are closely associated with known migraine pathophysiology, which could lead to the first reliable epigenetic biomarker set. Further studies should be performed to validate these findings in a larger and more heterogeneous sample.This study was solely funded by the Migraine Research Foundation

InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers

Antidepressiu; Migranya; Tractament preventiuAntidepresivo; Migraña; Tratamiento preventivoAntidepressant; Migraine; Preventive treatmentBackground There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. Methods This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. Results A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. Conclusions There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.This work did not receive any funds

Assessment of Professional Skills for Engineering at the Universidad Rosario Castellanos of CDMX

En ocasiones, desde el área de Ingeniería el conocimiento técnico se sobrepone a las competencias profesionales. Sin embargo, es importante desarrollar competencias profesionales desde la formación académica, tales como comunicación oral, resolución de problemas y trabajo en equipo con el fin de que los egresados cuenten con mayores oportunidades de inserción en el campo laboral. En el presente trabajo, se plantea valorar la mejora de estas competencias y mostrar los cambios observados en las competencias profesionales mediante el uso de la evidencia integradora que los estudiantes de ICAT desarrollan, derivado de la propuesta de solución de problemas prototípicos y su presentación en un evento académico a través de escenarios reales mediante incidentes críticos, que son parte del modelo educativo híbrido-dual que se implementa dentro de la Universidad Rosario Castellanos, propiciando un trabajo colaborativo que permita fomentar el desarrollo de habilidades, competencias y actitudes que los preparen mejor para su futura inserción en el mercado laboral.Sometimes, in the field of Engineering, technical knowledge takes precedence over professional skills. However, it is important to develop professional competencies from academic education, such as oral communication, problem- solving and teamwork, so that graduates have better oportunities for integration into the labor market. In this paper, we aim to assess the improvement of these competencies and demostrate the observed changes in professional skills through the use of integrative evidence that ICAT students develop, stemming from the proposed solution of prototypical problems within real-world scenarios and their presentation in an academic event through critical incidents. These incidents are part of the hybrid-dual educational model implemented at Universidad Rosario Castellanos, fostering collaborative work that enables the development of skills, competences, and attitudes that better prepare students for their future integration into the labor market

CXCR7 expression in diffuse large B-cell lymphoma identifies a subgroup of CXCR4+ patients with good prognosis

© 2018 Moreno et al.The CXCR4/CXCL12 axis has been extensively associated with different types of cancer correlating with higher aggressiveness and metastasis. In diffuse large B-cell lymphoma (DLBCL), the expression of the chemokine receptor CXCR4 is involved in the dissemination of malignant B cells and is a marker of poor prognosis. CXCR7 is a chemokine receptor that binds to the same ligand as CXCR4 and regulates de CXCR4-CXCL12 axis. These findings together with the report of CXCR7 prognostic value in several tumor types, led us to evaluate the expression of CXCR7 in diffuse large B-cell lymphoma biopsies. Here, we describe that CXCR7 receptor is an independent prognostic factor that associates with good clinical outcome. Moreover, the expression of CXCR7 associates with increased survival in CXCR4+ but not in CXCR4- DLBCL patients. Thus, the combined immunohistochemical evaluation of both CXCR7 and CXCR4 expression in DLBCL biopsies may improve their prognostic value as single markers. Finally, we show that CXCR7 overexpression in vitro is able to diminish DLBCL cell survival and increase their sensitivity to antitumor drugs. Hence, further studies on the CXCR7 receptor may establish its role in DLBCL and the molecular mechanisms that modulate CXCR4 activity.This work was supported by Instituto de Salud Carlos III (co-founding from FEDER) [ FIS PI11/00872, RD12/0036/0071, FIS PI14/00450 to J.S., FIS PI15/00378 to R.M., PIE15/00028 to R.M. and J.S., RD12/0036/0069, PS09/01382 to M.G.D, PI15/01393 to M.A, CD13/00074 to V.P.]; Centro de Investigación Biomédica en Red (CIBER) [CB06/01/1031 and Nanomets3 to R.M. and CB16/12/00233 to M.G.D.]; Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) [2014-SGR-1041, 2014PROD0005 to R.M and 2014-SGR-1281 to J.S]; Fundació La Marató TV3 [416/C/2013-2030 to R.M, 100830/31/32 to J.S and M.G.D.]; Josep Carreras Leukaemia Research Institute [P/AG 2014 to R.M.]; the Health Council of Castilla y León (BIO/SA56/13 and BIO/SA78/15 to M.A.); Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) [2017FI_B00680 to A.F.]

Object detection, distributed cloud computing and parallelization techniques for autonomous driving systems.

Autonomous vehicles are increasingly becoming a necessary trend towards building the smart cities of the future. Numerous proposals have been presented in recent years to tackle particular aspects of the working pipeline towards creating a functional end-to-end system, such as object detection, tracking, path planning, sentiment or intent detection, amongst others. Nevertheless, few efforts have been made to systematically compile all of these systems into a single proposal that also considers the real challenges these systems will have on the road, such as real-time computation, hardware capabilities, etc. This paper reviews the latest techniques towards creating our own end-to-end autonomous vehicle system, considering the state-of-the-art methods on object detection, and the possible incorporation of distributed systems and parallelization to deploy these methods. Our findings show that while techniques such as convolutional neural networks, recurrent neural networks, and long short-term memory can effectively handle the initial detection and path planning tasks, more efforts are required to implement cloud computing to reduce the computational time that these methods demand. Additionally, we have mapped different strategies to handle the parallelization task, both within and between the networks

OnabotulinumtoxinA: An Effective Tool in the Therapeutic Arsenal for Chronic Migraine With Medication Overuse

Objective: To evaluate the early response of onabotulinumtoxinA as a treatment tool in patients with chronic migraine (CM) and medication overuse (MO).Patients and Methods: This is a retrospective study in patients with CM and MO who received two cycles of onabotulinumtoxinA infiltrations following PREEMPT protocol. We evaluated the efficacy of onabotulinumtoxinA in MO resolution, defined as less than 10 days/month of acute medication intake (triptans, opioids, and combinations) or 15 days/month (non-steroidal anti-inflammatory drugs - and simple analgesics). In addition, we analyzed changes in headache frequency, pain intensity, and headache-related disability (MIDAS scale). A multivariate analysis was carried out to identify factors independently related to MO resolution.Results: We included 139 consecutive patients with CM and MO. After 2 cycles of onabotulinumtoxinA, 73.4% had ≥50% reduction in acute medication intake and 57.6% achieved MO resolution. 7.9% of patients did not use any acute medication after treatment. Even though both MO-ongoing group and MO-resolution group improve in headache frequency, the reduction was significantly higher for the group which discontinued the use of acute medication after onabotulinumtoxinA treatment (p &lt; 0.001). In this group, 73.0% reduced headache frequency ≥50%. Daily headache changed from 71.2 to 23.2% (p &lt; 0.001). Both groups showed an improvement in pain intensity and in MIDAS score (p &lt; 0.05). In the multivariate analysis we observed that MO resolution had an inverse association with medication intake at baseline (OR:0.294, p &lt; 0.05) and a direct association with frequency (OR:20.455, p &lt; 0.001) and MIDAS score (OR: 6.465, p &lt; 0.05) improvements.Conclusion: OnabotulinumtoxinA has an early beneficial effect on the discontinuation of acute medication in a substantial proportion of patients with CM and MO. Therefore, onabotulinumtoxinA might be considered a therapeutic tool in CM with MO

Variability of coil inductance measurements inside an interleaving structure

The present article is a continuation of our previous works on the anomalies in the decay rates and the capacitance measurements inside a modified Faraday cage. Here we present the anomalous variations in the measurements of inductance when a coil is placed inside an interleaving structure of metal and organic material. The fluctuation in the inductance values was found to be in the range − 0.007 to 0.018 mH. Additionally, it was observed that the temperature coefficient which was 0.0062 mH/°C initially jumped to two distinct levels, 0.0095 mH/°C and 0.0145 mH/°C, respectively. A multiple factor analysis of our results revealed a very strong correlation (R2 = 95.2%) between the inductance and the combination of the temperature and the relative humidity both measured inside the cage, next to the inductor.DGAPA-UNAM (Mexico) | Ref. IN103522Ministerio de Ciencia e Innovación | Ref. PID2021-128676OB-I0

Investigation of Low-lying States in 133Sn Populated in the β Decay of 133In Using Isomer-selective Laser Ionization

Excited states in the neutron-rich isotope Sn-133 were studied via the beta decay of In-133. Isomer selective ionization using the ISOLDE RILIS enabled the beta decays of In-133(gs) (I-pi = 9/2(+)) and In-133m (I-pi = 1/2(-)) to be studied independently for the first time. A description of the experimental setup at the ISOLDE Decay Station is presented together with preliminary results from the experiment