Evaluation of p53, Caspase-3, Bcl-2, and Ki-67 markers in oral squamous cell carcinoma and premalignant epithelium in a sample from Alava Province (Spain)

Objectives: The objective of this study was to determine whether alterations in the expression of p53, caspase-3 Bcl-2, and ki-67 appear early in premalignant oral epithelium and show clonal behavior. Study Design: Samples from 41 tumors with their adjacent non-tumor epithelia were immunohistochemically analyzed using monoclonal antibodies that recognize p53, caspase-3, Bcl-2, and Ki-67 Results: A statistically significant association was found between the expression in tumor and adjacent epithelium of p53, caspase-3, and Bcl-2 but not of k-67. A significant association was observed between the expression of ki-67 and p53 in both localizations. In non-tumor (premalignant) epithelium samples, there was a significant inverse relationship between the expressions of p53 and caspase-3 and a significant direct relationship between the expressions of p53 and Bcl-2. Conclusions: Alterations in these proteins appear to operate in combination with premalignant epithelia to create hyperproliferative cell states that favor the acquisition of summative oncogenic errors that confer invasive capacity

When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Neurobehavioral Progress

[EN] Accurate estimation of the neurobehavioral progress of patients with unresponsive wakefulness syndrome (UWS) is essential to anticipate their most likely clinical course and guide clinical decision making. Although different studies have described this progress and possible predictors of neurobehavioral improvement in these patients, they have methodological limitations that could restrict the validity and generalization of the results. This study investigates the neurobehavioral progress of 100 patients with UWS consecutively admitted to a neurorehabilitation center using systematic weekly assessments based on standardized measures, and the prognostic factors of changes in their neurobehavioral condition. Our results showed that, during the analyzed period, 34% of the patients were able to progress from UWS to minimally conscious state (MCS), 12% of the total sample (near one third from those who progressed to MCS) were able to emerge from MCS, and 10% of the patients died. Transition to MCS was mostly denoted by visual signs, which appeared either alone or in combination with motor signs, and was predicted by etiology and the score on the Coma Recovery Scale-Revised at admission with an accuracy of 75%. Emergence from MCS was denoted in the same proportion by functional communication and object use. Predictive models of emergence from MCS and mortality were not valid and the identified predictors could not be accounted forThis research was funded by the program RISE-Marie-Slodowska-Curie of the European Commission (Grant agreement 778234), by Conselleria de Educacion, Investigacion, Cultura y Deporte of Generalitat Valenciana (SEJI/2019/017), and by Vicerrectorado de Investigacion, Innovacion y transferencia of Universitat Politecnica de Valencia (PAID-06-18)Noé Sebastián, E.; Ferri, J.; Olaya, J.; Navarro, MD.; O'valle, M.; Colomer Font, C.; Moliner, B.... (2021). When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Neurobehavioral Progress. Brain Sciences. 11(1):1-16. https://doi.org/10.3390/brainsci11010126S11611

Combined Transcranial Direct Current Stimulation and Virtual Reality-Based Paradigm for Upper Limb Rehabilitation in Individuals with Restricted Movements. A Feasibility Study with a Chronic Stroke Survivor with Severe Hemiparesis

[EN] Impairments of the upper limb function are a major cause of disability and rehabilitation. Most of the available therapeutic options are based on active exercises and on motor and attentional inclusion of the affected arm in task oriented movements. However, active movements may not be possible after severe impairment of the upper limbs. Different techniques, such as mirror therapy, motor imagery, and non-invasive brain stimulation have been shown to elicit cortical activity in absence of movements, which could be used to preserve the available neural circuits and promote motor learning. We present a virtual reality-based paradigm for upper limb rehabilitation that allows for interaction of individuals with restricted movements from active responses triggered when they attempt to perform a movement. The experimental system also provides multisensory stimulation in the visual, auditory, and tactile channels, and transcranial direct current stimulation coherent to the observed movements. A feasibility study with a chronic stroke survivor with severe hemiparesis who seemed to reach a rehabilitation plateau after two years of its inclusion in a physical therapy program showed clinically meaningful improvement of the upper limb function after the experimental intervention and maintenance of gains in both the body function and activity. The experimental intervention also was reported to be usable and motivating. Although very preliminary, these results could highlight the potential of this intervention to promote functional recovery in severe impairments of the upper limb.This study was funded in part by Ministerio de Economia y Competitividad of Spain (Project TIN2014-61975-EXP and Grant BES-2014-068218) and by Universitat Politecnica de Valencia (Grant PAID-10-14 and Grant PAID-10-16).Fuentes Calderón, MA.; Borrego, A.; Latorre Grau, J.; Colomer Font, C.; Alcañiz Raya, ML.; Sánchez-Ledesma, MJ.; Noé-Sebastián, E.... (2018). Combined Transcranial Direct Current Stimulation and Virtual Reality-Based Paradigm for Upper Limb Rehabilitation in Individuals with Restricted Movements. A Feasibility Study with a Chronic Stroke Survivor with Severe Hemiparesis. Journal of Medical Systems. 42(5):1-9. https://doi.org/10.1007/s10916-018-0949-yS19425Invernizzi, M., Negrini, S., Da, S. C., Lanzotti, L., Cisari, C., and Baricich, A., The value of adding mirror therapy for upper limb motor recovery of subacute stroke patients: A randomized controlled trial. Eur. J. Phys. Rehabil. Med. 49:311–317, 2013.Park, Y., Chang, M., Kim, K.-M., and An, D.-H., The effects of mirror therapy with tasks on upper extremity function and self-care in stroke patients. J. Phys. Ther. Sci. 27:1499–1501, 2015. https://doi.org/10.1589/jpts.27.1499 .Pollock, A., Farmer, S. E., Brady, M. C., Langhorne, P., Mead, G. E., Mehrholz, J., and van Wijck, F., Interventions for improving upper limb function after stroke. Cochrane Database Syst. Rev. 11, 2014. https://doi.org/10.1002/14651858.CD010820.pub2 .Barker, R. N., Gill, T. J., and Brauer, S. G., Factors contributing to upper limb recovery after stroke: A survey of stroke survivors in Queensland Australia. Disabil. Rehabil. 29:981–989, 2007. https://doi.org/10.1080/09638280500243570 .Bayona, N. A., Bitensky, J., Salter, K., and Teasell, R., The role of task-specific training in rehabilitation therapies. Top. Stroke Rehabil. 12:58–65, 2005. https://doi.org/10.1310/BQM5-6YGB-MVJ5-WVCR .Coupar, F., Pollock, A., Rowe, P., Weir, C., and Langhorne, P., Predictors of upper limb recovery after stroke: a systematic review and meta-analysis. Clin. Rehabil. 26:291–313, 2012. https://doi.org/10.1177/0269215511420305 .Hunter, S. M., Crome, P., Sim, J., and Pomeroy, V. M., Effects of Mobilization and Tactile Stimulation on Recovery of the Hemiplegic Upper Limb: A Series of Replicated Single-System Studies. Arch. Phys. Med. Rehabil. 89:2003–2010, 2008. https://doi.org/10.1016/j.apmr.2008.03.016 .Colomer, C., Noé, E., and Llorens, R., Mirror therapy in chronic stroke survivors with severely impaired upper limb function: A randomized controlled trial. Eur. J. Phys. Rehabil. Med. 52:271–278, 2016.Lum, P. S., Mulroy, S., Amdur, R. L., Requejo, P., Prilutsky, B. I., and Dromerick, A. W., Gains in upper extremity function after stroke via recovery or compensation: Potential differential effects on amount of real-world limb use. Top. Stroke Rehabil. 16:237–253, 2009. https://doi.org/10.1310/tsr1604-237 .Taub, E., Uswatte, G., Mark, V. W., and Morris, D. M. M., The learned nonuse phenomenon: implications for rehabilitation. Eura. Medicophys. 42:241–256, 2006.Deconinck, F. J. A., Smorenburg, A. R. P., Benham, A., Ledebt, A., Feltham, M. G., and Savelsbergh, G. J. P., Reflections on Mirror Therapy: A Systematic Review of the Effect of Mirror Visual Feedback on the Brain. Neurorehabil. Neural Repair. 29:349–361, 2014. https://doi.org/10.1177/1545968314546134 .Lindberg, P. G., Schmitz, C., Engardt, M., Forssberg, H., and Borg, J., Use-dependent up- and down-regulation of sensorimotor brain circuits in stroke patients. Neurorehabil. Neural Repair. 21:315–326, 2007. https://doi.org/10.1177/1545968306296965 .Thieme, H., Bayn, M., Wurg, M., Zange, C., Pohl, M., and Behrens, J., Mirror therapy for patients with severe arm paresis after stroke--a randomized controlled trial. Clin. Rehabil. 27:314–324, 2013. https://doi.org/10.1177/0269215512455651 .Dettmers, C., Benz, M., Liepert, J., and Rockstroh, B., Motor imagery in stroke patients, or plegic patients with spinal cord or peripheral diseases. Acta Neurol. Scand. 126:238–247, 2012. https://doi.org/10.1111/j.1600-0404.2012.01680.x .Kimberley, T. J., Khandekar, G., Skraba, L. L., Spencer, J. A., Van Gorp, E. A., and Walker, S. R., Neural substrates for motor imagery in severe hemiparesis. Neurorehabil. Neural Repair. 20:268–277, 2006. https://doi.org/10.1177/1545968306286958 .Pascual-Leone, A., The neuronal correlates of mirror therapy: an fMRI study on mirror induced visual illusions in patients with stroke. J. Neurol. Neurosurg. Psychiatry. 82:393–398, 2011. https://doi.org/10.1136/jnnp.2009.194134 .Gatti, R., Rocca, M. A., Fumagalli, S., Cattrysse, E., Kerckhofs, E., Falini, A., and Filippi, M., The effect of action observation/execution on mirror neuron system recruitment: an fMRI study in healthy individuals. Brain Imaging Behav. 11:565–576, 2017. https://doi.org/10.1007/s11682-016-9536-3 .Bonato, C., Miniussi, C., and Rossini, P. M., Transcranial magnetic stimulation and cortical evoked potentials: A TMS/EEG co-registration study. Clin. Neurophysiol. 117:1699–1707, 2006. https://doi.org/10.1016/j.clinph.2006.05.006 .Grundmann, L., Rolke, R., Nitsche, M. A., Pavlakovic, G., Happe, S., Treede, R. D., Paulus, W., and Bachmann, C. G., Effects of transcranial direct current stimulation of the primary sensory cortex on somatosensory perception. Brain Stimul. 4:253–260, 2011. https://doi.org/10.1016/j.brs.2010.12.002 .von Rein, E., Hoff, M., Kaminski, E., Sehm, B., Steele, C. J., Villringer, A., and Ragert, P., Improving motor performance without training: the effect of combining mirror visual feedback with transcranial direct current stimulation. J. Neurophysiol. 113:2383–2389, 2015. https://doi.org/10.1152/jn.00832.2014 .Kim, Y. J., Ku, J., Cho, S., Kim, H. J., Cho, Y. K., Lim, T., and Kang, Y. J., Facilitation of corticospinal excitability by virtual reality exercise following anodal transcranial direct current stimulation in healthy volunteers and subacute stroke subjects. J. Neuroeng. Rehabil. 11:124, 2014. https://doi.org/10.1186/1743-0003-11-124 .S. Bermúdez i Badia, G.G. Fluet, R. Llorens, J.E. Deutsch, Virtual Reality for Sensorimotor Rehabilitation Post Stroke: Design Principles and Evidence. In: Neurorehabilitation Technol., Second edi, Springer, 2016: pp. 573–603. https://doi.org/10.1007/978-3-319-28603-7_28 .Im, H., Ku, J., Kim, H. J., and Kang, Y. J., Virtual reality-guided motor imagery increases corticomotor excitability in healthy volunteers and stroke patients. Ann. Rehabil. Med. 40:420–431, 2016. https://doi.org/10.5535/arm.2016.40.3.420 .Colomer, C., Llorens, R., Noé, E., and Alcañiz, M., Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke. J. Neuroeng. Rehabil. 13, 2016. https://doi.org/10.1186/s12984-016-0153-6 .Grimm, F., Naros, G., and Gharabaghi, A., Closed-Loop Task Difficulty Adaptation during Virtual Reality Reach-to-Grasp Training Assisted with an Exoskeleton for Stroke Rehabilitation. Front. Neurosci. 10:518, 2016. https://doi.org/10.3389/fnins.2016.00518 .Poole, A., and Ball, L. J., Eye Tracking in Human-Computer Interaction and Usability Research: Current Status and Future Prospects. Encycl. Human-Computer Interact.:211–219, 2005. https://doi.org/10.4018/978-1-59140-562-7 .R. Merletti, A. Botter, A. Troiano, E. Merlo, M.A. Minetto, Technology and instrumentation for detection and conditioning of the surface electromyographic signal: State of the art, Clin. Biomech. 24 (2009) 122–134. https://doi.org/10.1016/j.clinbiomech.2008.08.006 .Trojano, L., Moretta, P., Loreto, V., Cozzolino, A., Santoro, L., and Estraneo, A., Quantitative assessment of visual behavior in disorders of consciousness. J. Neurol. 259:1888–1895, 2012. https://doi.org/10.1007/s00415-012-6435-4 .Trojano, L., Moretta, P., Loreto, V., Santoro, L., and Estraneo, A., Affective saliency modifies visual tracking behavior in disorders of consciousness: A quantitative analysis. J. Neurol. 260:306–308, 2013. https://doi.org/10.1007/s00415-012-6717-x .Sanford, J., Moreland, J., Swanson, L. R., Stratford, P. W., and Gowland, C., Reliability of the Fugl-Meyer assessment for testing motor performance in patients following stroke. Phys. Ther. 73:447–454, 1993. https://doi.org/10.1177/1545968304269210 .Lang, C. E., Edwards, D. F., Birkenmeier, R. L., and Dromerick, A. W., Estimating Minimal Clinically Important Differences of Upper-Extremity Measures Early After Stroke. Arch. Phys. Med. Rehabil. 89:1693–1700, 2008. https://doi.org/10.1016/j.apmr.2008.02.022 .Brooke, J., SUS - A quick and dirty usability scale. Usability Eval. Ind. 189:4–7, 1996. https://doi.org/10.1002/hbm.20701 .McAuley, E., Duncan, T., and Tammen, V. V., Psychometric Properties of the Intrinsic Motivation Inventory in a Competitive Sport Setting: A Confirmatory Factor Analysis. Res. Q. Exerc. Sport. 60:48–58, 1989. https://doi.org/10.1080/02701367.1989.10607413 .Page, S. J., Fulk, G. D., and Boyne, P., Clinically important differences for the upper-extremity Fugl-Meyer Scale in people with minimal to moderate impairment due to chronic stroke. Phys. Ther. 92:791–798, 2012. https://doi.org/10.2522/ptj.20110009 .R. Teasell, Evidence-Based Review of Stroke Rehabilitation - Background Concepts in Stroke Rehabilitation, 2016. http://www.ebrsr.com/evidence-review/3-background-concepts-stroke-rehabilitation .Cameirão, M. S., Badia, S. B. I., Duarte, E., Frisoli, A., and Verschure, P. F. M. J., The combined impact of virtual reality neurorehabilitation and its interfaces on upper extremity functional recovery in patients with chronic stroke. Stroke. 43:2720–2728, 2012. https://doi.org/10.1161/STROKEAHA.112.653196 .K.E. Laver, S. George, S. Thomas, J.E. Deutsch, M. Crotty, Virtual reality for stroke rehabilitation. In: Cochrane Database Syst. Rev., 2015: pp. 1–107. https://doi.org/10.1002/14651858.CD008349.pub3 .Lefebvre, S., Laloux, P., Peeters, A., Desfontaines, P., Jamart, J., and Vandermeeren, Y., Dual-tDCS Enhances Online Motor Skill Learning and Long-Term Retention in Chronic Stroke Patients. Front. Hum. Neurosci. 6:343, 2012. https://doi.org/10.3389/fnhum.2012.00343 .Lindenberg, R., Renga, V., Zhu, L. L., Nair, D., and Schlaug, G., Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients. Neurology. 75:2176–2184, 2010. https://doi.org/10.1212/WNL.0b013e318202013a .K. Figlewski, J.U. Blicher, J. Mortensen, K.E. Severinsen, J.F. Nielsen, H. Andersen, Transcranial Direct Current Stimulation Potentiates Improvements in Functional Ability in Patients With Chronic Stroke Receiving Constraint-Induced Movement Therapy, Stroke. (2016). http://stroke.ahajournals.org/content/early/2016/11/29/STROKEAHA.116.014988.abstract .Lee, S. J., and Chun, M. H., Combination transcranial direct current stimulation and virtual reality therapy for upper extremity training in patients with subacute stroke. Arch. Phys. Med. Rehabil. 95:431–438, 2014. https://doi.org/10.1016/j.apmr.2013.10.027 .Viana, R. T., Laurentino, G. E. C., Souza, R. J. P., Fonseca, J. B., Silva Filho, E. M., Dias, S. N., Teixeira-Salmela, L. F., and Monte-Silva, K. K., Effects of the addition of transcranial direct current stimulation to virtual reality therapy after stroke: A pilot randomized controlled trial. NeuroRehabilitation. 34:437–446, 2014. https://doi.org/10.3233/NRE-141065 .Sigrist, R., Rauter, G., Riener, R., and Wolf, P., Augmented visual, auditory, haptic, and multimodal feedback in motor learning: A review. Psychon. Bull. Rev. 20:21–53, 2013. https://doi.org/10.3758/s13423-012-0333-8 .Bowering, K. J., O’Connell, N. E., Tabor, A., Catley, M. J., Leake, H. B., Moseley, G. L., and Stanton, T. R., The Effects of Graded Motor Imagery and Its Components on Chronic Pain: A Systematic Review and Meta-Analysis. J. Pain. 14:3–13, 2013. https://doi.org/10.1016/j.jpain.2012.09.007

Current validity of diagnosis of permanent vegetative state: a longitudinal study in a sample of patients with altered states of consciousness

[EN] Introduction Altered states of consciousness have traditionally been associated with poor prognosis. At present, clinical differences between these entities are beginning to be established. Method Our study included 37 patients diagnosed with vegetative state/unresponsive wakefulness syndrome (UWS) and 43 in a minimally conscious state (MCS) according to the Coma Recovery Scale¿Revised (CRS-R). All patients were followed up each month for at least 6 months using the CRS-R. We recorded the time points when vegetative state progressed from `persistent¿ to `permanent¿ based on the cut-off points established by the Multi-Society-Task-Force: 12 months in patients with traumatic injury and 3 months in those with non-traumatic injury. A logistic regression model was used to determine the factors potentially predicting which patients will emerge from MCS. Results In the UWS group, 23 patients emerged from UWS but only 9 emerged from MCS. Of the 43 patients in the MCS group, 26 patients emerged from that state during follow-up. Eight of the 23 patients (34.7%) who emerged from UWS and 17 of the 35 (48.6%) who emerged from MCS recovered after the time points proposed by the Multi-Society-Task-Force. According to the multivariate regression analysis, aetiology (P < .01), chronicity (P = .01), and CRS-R scores at admission (P < .001) correctly predicted emergence from MCS in 77.5% of the cases. Conclusions UWS and MCS are different clinical entities in terms of diagnosis and outcomes. Some of the factors traditionally associated with poor prognosis, such as time from injury and likelihood of recovery, should be revaluated.[ES] Introducción Los estados alterados de conciencia han sido considerados tradicionalmente como cuadros clínicos de pronóstico infausto. En la actualidad, sabemos que dichos estados engloban distintas entidades clínicas cuyo perfil diferencial empieza a reconocerse. Método Se incluyeron 37 pacientes con el diagnóstico de estado vegetativo o síndrome de vigilia sin respuesta (SVSR) y 43 en estado de mínima conciencia (EMC) de acuerdo con la Coma Recovery Scale-Revised (CRS-R). Todos los pacientes fueron evaluados mensualmente con la CRS-R durante al menos 6 meses. Se evaluó el momento de superar cada estado considerando los puntos de corte de «irreversibilidad» (12 meses para los casos de origen traumático y 3 para los no traumáticos), tradicionalmente establecidos por la Multi-Society-Task-Force. Se empleó un modelo de regresión logística para determinar las variables predictoras de superar el EMC. Resultados Un total de 23 pacientes en SVSR superaron este estado, pero solo 9 superaron el EMC. De los 43 pacientes en EMC al ingreso, 26 lograron superarlo. Ocho de los 23 (34,7%) pacientes que superaron el SVSR y 17 de los 35 (48,6%) que superaron el EMC lo hicieron más allá del punto de «irreversibilidad». La etiología (p < 0,01), la cronicidad (p = 0,01) y la puntuación en la CRS-R (p < 0,001) predijeron la salida de EMC en el modelo multivariante con un 77,5% de acierto. Conclusiones Tanto el SVRS como el EMC son entidades clínicamente diferenciadas en términos diagnósticos y pronósticos. Algunos criterios clásicos relacionados con el mal pronóstico de estos estados en términos de tiempo y posibilidades de recuperación deben ser reevaluados.Noé -Sebastián, E.; Olaya, J.; Colomer Font, C.; Moliner, B.; Ugart, P.; Llorens Rodríguez, R.; Rodríguez -Sánchez-Leiva, C.... (2019). Validez actual del diagnóstico de estado vegetativo permanente : estudio longitudinal en una muestra clínica de pacientes en estado alterado de conciencia. Neurología. 34(9):589-595. https://doi.org/10.1016/j.nrl.2017.04.004S58959534

Two independent epigenetic biomarkers predict survival in neuroblastoma

Background: Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with a highly variable clinical course, ranging from spontaneous regression to life-threatening disease. Survival rates for high-risk NB patients remain disappointingly low despite multimodal treatment. Thus, there is an urgent clinical need for additional biomarkers to improve risk stratification, treatment management, and survival rates in children with aggressive NB. Results: Using gene promoter methylation analysis in 48 neuroblastoma tumors with microarray technology, we found a strong association between survival and gene promoter hypermethylation (P = 0.036). Hypermethylation of 70 genes significantly differentiated high-risk survivor patients from those who died during follow-up time. Sixteen genes with relevant roles in cancer biology were further validated in an additional cohort of 83 neuroblastoma tumors by bisulfite pyrosequencing. High promoter methylation rates of these genes were found in patients with metastatic tumors (either stage metastatic (M) or metastatic special (MS)), 18 months or older at first diagnosis, MYCN amplification, relapsed, and dead. Notably, the degree of methylation of retinoblastoma 1 (RB1) and teratocarcinoma-derived growth factor 1 (TDGF1) predicts event-free and overall survival independently of the established risk factors. In addition, low RB1 mRNA expression levels associate with poor prognosis suggesting that promoter methylation could contribute to the transcriptional silencing of this gene in NB. Conclusions: We found a new epigenetic signature predictive for NB patients' outcome: the methylation status of RB1 and TDGF1 associate with poorer survival. This information is useful to assess prognosis and improve treatment selection

Atrial Fibrillation Originating in the Inferior Vena Cava

Recurrence of atrial fibrillation (AF) despite successful isolation of the pulmonary veins (PVs) represents a great challenge. We present a patient with recurrent episodes of paroxysmal AF despite PV isolation in which a non-PV trigger was identified in the inferior vena cava. (Level of Difficulty: Intermediate.

Influence of sex on intracellular calcium homoeostasis in patients with atrial fibrillation

Altres ajuts: Fundació Marato TV3 [20152030/31].Atrial fibrillation (AF) has been associated with intracellular calcium disturbances in human atrial myocytes, but little is known about the potential influence of sex and we here aimed to address this issue. Alterations in calcium regulatory mechanisms were assessed in human atrial myocytes from patients without AF or with long-standing persistent or permanent AF. Patch-clamp measurements revealed that L-type calcium current (I ) density was significantly smaller in males with than without AF (−1.15 ± 0.37 vs. −2.06 ± 0.29 pA/pF) but not in females with AF (−1.88 ± 0.40 vs. −2.21 ± 0.0.30 pA/pF). In contrast, transient inward currents (I ) were more frequent in females with than without AF (1.92 ± 0.36 vs. 1.10 ± 0.19 events/min) but not in males with AF. Moreover, confocal calcium imaging showed that females with AF had more calcium spark sites than those without AF (9.8 ± 1.8 vs. 2.2 ± 1.9 sites/µm 2) and sparks were wider (3.0 ± 0.3 vs. 2.2 ± 0.3 µm) and lasted longer (79 ± 6 vs. 55 ± 8 ms), favouring their fusion into calcium waves that triggers I s and afterdepolarizations. This was linked to higher ryanodine receptor phosphorylation at s2808 in women with AF, and inhibition of adenosine A or beta-adrenergic receptors that modulate s2808 phosphorylation was able to reduce the higher incidence of I in women with AF. Perturbations of the calcium homoeostasis in AF is sex-dependent, concurring with increased spontaneous SR calcium release-induced electrical activity in women but not in men, and with diminished I density in men only. This work was supported by grants from The Spanish Ministry of Science Innovation and Universities

Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days old) Duroc breed females (n=21) either with a standard growth diet (3800 kcal/day) or one with a high-calorie content (5200 kcal/day) during 70 days. Computerized tomography, mass-spectrometry-based metabolomics and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake. Samples from a human cohort confirmed potential lipidomic markers. Compared to those fed a standard growth diet, pigs fed a high-calorie diet showed an increased weight gain (13%), much higher adiposity (53%), hypertriacylglyceridemia and hypercholesterolemia in parallel to insulin resistance. This diet induced marked changes in the circulating lipidome, particularly in phosphatidylethanolamine-type molecules. Also, circulating specific diacylglycerol and monoacylglycerol contents correlated with visceral fat and intrahepatic triacylglycerol concentrations. Specific lipids associated with obesity in swine (mainly belonging to glycerophospholipid, triacylglyceride and sterol classes) were also linked with obesity traits in the human cohort, reinforcing the usefulness of the chosen approach. Interestingly, no overt inflammation in plasma or adipose tissue was evident in this model. The presented model is useful as a preclinical surrogate of prepubertal obesity in order to ascertain the pathophysiology interactions between energy intake and obesity development.Supported by Centro para el Desarrollo Tecnológico e Industrial, Spain, Project reference: IPT-20111008, and Generalitat de Catalunya grants 2017SGR1719 and 2017SGR696. MJ is a "Serra Hunter" program fellow. Supported by Instituto de Salud Carlos III, Spain, Project reference: 17-00134, co-financed by FEDER Funds A way to make Europe

Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO

Background To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi). Methods The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (>= 4 years) and (ii) no long-term treatment (= 2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (>= 4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP). Conclusions Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease

Viceversos: Trasvases metodológicos en el paisaje (entre Geografía, Sociología y Arquitectura)

El objetivo de la Red ha sido compartir metodologías de detección, análisis y proyecto en la interacción entre sociedad y paisaje en áreas específicas del Levante español, metodologías que pudieran ser ensayadas por estudiantes de Sociología, Arquitectura y Geografía en la Universidad de Alicante en el marco de sus prácticas de campo en sus asignaturas de Grado.El ámbito socio-geográfico preciso ha sido el término municipal de Sella en la Marina Baixa, incluyendo unos valles del término municipal de Benimantell cuyo acceso natural se produce desde Sella. Los objetivos básicos de las metodologías compartidas se han referido a cómo el paisaje semiabandonado y abancalado junto a ríos y acequias presenta trazas identitarias aprovechables (sendas de montaña que conectan masías, enclaves geomorfológicos, fincas en desuso, cuencas visuales, masas forestales…) para encontrar nuevos usos y formas de habitar el espacio natural, o formas de paisaje convertible en aula de escuela primaria, o formas lúdico-musicales de disfrute en la naturaleza.El trabajo de los integrantes de la Red consistió en diseñar los protocolos de interacción para situaciones flexibles dentro de los cronogramas formativos reglados (Grados de Sociología, Arquitectura, Geografía) definiendo sesiones de colaboración, desplazamientos al lugar, metodologías compartidas y encuentros para debatir los resultados. Los resultados de la experiencia se han llegado a publicar por el momento en dos comunicaciones en Congresos y Jornadas de Redes en la UA