Synesthesia: a return to the body

Synesthesia is a neurological phenomenon whose nature and etiology remain unknown. In this paper, I apply the neurophenomenological perspective to reflect on the very nature of inducers and concurrents, including their perceptual and conceptual dimensions and their stability over time. Additionally, I analyze the role of attention and its influence over synesthesia, which contributes to the difficulties that we, synesthetes, find when sharing our personal experiences with non-synesthetes. Finally, I expose some examples of the current neuroscientific data and propose some insights into the embodied character of synesthesia, stressing the key role of its emotional component. I conclude describing the clinical applications of the findings in the field of synesthesia and their implications for the understanding of cognition in general

Grapheme-color synesthetes show peculiarities in their emotional brain: cortical and subcortical evidence from VBM analysis of 3D-T1 and DTI data

Grapheme-color synesthesia is a neurological phenomenon in which viewing achromatic letters/numbers leads to automatic and involuntary color experiences. In this study, voxel-based morphometry analyses were performed on T1 images and fractional anisotropy measures to examine the whole brain in associator grapheme-color synesthetes. These analyses provide new evidence of variations in emotional areas (both at the cortical and subcortical levels), findings that help understand the emotional component as a relevant aspect of the synesthetic experience. Additionally, this study replicates previous findings in the left intraparietal sulcus and, for the first time, reports the existence of anatomical differences in subcortical gray nuclei of developmental grapheme-color synesthetes, providing a link between acquired and developmental synesthesia. This empirical evidence, which goes beyond modality-specific areas, could lead to a better understanding of grapheme-color synesthesia as well as of other modalities of the phenomenon

UC3M Books

Divulgación de los libros: Cómo informar sobre la violencia machista, de José María Fernández Calleja; Cuídate, cuídalos: para prevenir la violencia de género, de Helena Soleto; La escalera oscura, de Alejandro Melero; Dentro de El Ministerio del Tiempo, de Concepción Cascajosa

Guava: phytochemical composition of a potential source of antioxidants for cosmetic and/or dermatological applications

Guava (Psidium guajava L.) is a native fruit of the American tropics with commercial applications for its taste, flavor and aroma. Numerous pharmacological uses have been described for it, such as the antiseptic effect of its leaves, the use of the fresh fruit and tea from its leaves for the treatment of diarrhea, dysentery, diabetes mellitus, and others. However, considering its rich composition, the guava also is a potential source of antioxidants to be used in the development of new formulations for cosmetic and/or dermatological applications, the main focus of this research. Herein, we describe the study of the phytochemical composition and the antioxidant activity of a guava extract prepared with non-toxic solvents aiming its use at biological applications. High performance liquid chromatography and mass spectrometry were employed to identify the major components, while thermoanalytical measurements and hot stage microscopy were used to assess the chemical stability of guava fruit extract. The antioxidant activity was also evaluated assessing the SOD-like activity and ABTS free radical scavenger. The results show that the extract is a rich source of phenolic compounds, such as quercetin, kaempferol, schottenol, among many others. All of the components found in guava extract exhibit biological effects according to the literature data, mainly antioxidant properties

Biomarkers of tumor-reactive CD4+ and CD8+ TILs associate with improved prognosis in endometrial cancer

Background: Despite the growing interest in immunotherapeutic interventions for endometrial cancer (EC), the prevalence, phenotype, specificity and prognostic value of tumor infiltrating lymphocytes (TILs) in this tumor type remains unclear. Methods: To better understand the role of TILs in EC, we analyzed the phenotypic traits of CD8+ and CD4+ EC-resident T cells from 47 primary tumors by high-dimensional flow cytometry. In addition, CD8+ and CD4+ TIL subpopulations were isolated based on the differential expression of programmed cell death protein-1 (PD-1) (negative, dim and high) and CD39 (positive or negative) by fluorescence activated cell sorting (FACS), expanded in vitro, and screened for autologous tumor recognition. We further investigated whether phenotypic markers preferentially expressed on CD8+ and CD4+ tumor-reactive TIL subsets were associated with the four distinct molecular subtypes of EC, tumor mutational burden and patient survival. Results: We found that CD8+TILs expressing high levels of PD-1 (PD-1hi) co-expressed CD39, TIM-3, HLA-DR and CXCL13, as compared with TILs lacking or displaying intermediate levels of PD-1 expression (PD-1- and PD-1dim, respectively). Autologous tumor reactivity of sorted and in vitro expanded CD8+ TILs demonstrated that the CD8+PD-1dimCD39+ and PD-1hiCD39+ T cell subsets both contained tumor-reactive TILs and that a higher level of PD-1 expression was associated with increased CD39 and a superior frequency of tumor reactivity. With respect to CD4+ T conventional (Tconv) TILs, co-expression of inhibitory and activation markers was more apparent on PD-1hi compared with PD-1- or PD-1dim T cells, and in fact, it was the CD4+PD-1hi subpopulation that accumulated the antitumor T cells irrespective of CD39 expression. Most importantly, detection of CD8+PD-1hiCD39+ and CD4+PD-1hi tumor-reactive T-cell subsets, but also markers specifically expressed by these subpopulations of TILs, that is, PD-1hi, CD39, CXCL13 and CD103 by CD8+ TILs and PD-1hi and CXCL13 by CD4+ Tconv TILs, correlated with prolonged survival of patients with EC. Conclusions: Our results demonstrate that EC are frequently infiltrated by tumor-reactive TILs, and that expression of PD-1hi and CD39 or PD-1hi can be used to select and expand CD8+ and CD4+ tumor-reactive TILs, respectively. In addition, biomarkers preferentially expressed on tumor-reactive TILs, rather than the frequency of CD3+, CD8+ and CD4+ lymphocytes, hold prognostic value suggesting their protective role in antitumor immunity

The interplay between functioning problems and symptoms in first episode of psychosis: an approach from network analysis

The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this populationThis work was supported by the Madrid Regional Government (R&D activities in Biomedicine (grant number S2017/BMD-3740 - AGES-CM 2-CM)) and Structural Funds of the European Union. Ana Izquierdo’s work is supported by the PFIS predoctoral program (FI17/00138) from the Instituto de Salud Carlos III (Spain) and co-funded by the European Union (ERDF/ESF, "A way to make Europe”/ “Investing in your future”) and The Biomedical Research Foundation of La Princesa University Hospital. Angela Ib´a˜nez thanks the support of CIBERSAM and of the Spanish Ministry of Science, Innovation and Universities. Instituto de Salud Carlos III (PI16/00834 and PI19/01295) co-financed by ERDF Funds from the European Commission. Covadonga M. Díaz-Caneja holds a Juan Rod´es Grant from Instituto de Salud Carlos III (JR19/00024). Celso Arango was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/ 024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH- 2013-2.2.1-2-603196 (Project PSYSCAN) and FP7- HEALTH-2013- 2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci´on Familia Alonso, Fundaci´on Alicia Koplowitz and Fundaci´on Mutua Madrile˜n

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Sinestesia, bases neuroanatómicas y cognitivas

La sinestesia es un fenómeno neurológico de carácter no patológico que aparece cuando la estimulación de una vía sensorial o cognitiva produce una experiencia asociada en una segunda vía que no ha sido estimulada directamente. A pesar de que en los últimos 15 años el estudio de la sinestesia ha dado lugar a más de 500 publicaciones científicas, sus bases neurofisiológicas aún no han sido dilucidadas. Para aportar nuevos datos empíricos sobre esta cuestión, en esta tesis doctoral se ha analizado el fenómeno de la sinestesia investigando la frecuencia relativa de sus diferentes modalidades, así como sus bases neuroanatómicas y cognitivas. La tesis se divide en tres partes. En la primera (Capítulo I), se lleva a cabo una revisión sobre el estado de la cuestión, incluyendo la definición del fenómeno y sus características, los datos de prevalencia, las diferentes modalidades catalogadas, la evidencia experimental acerca de las diferencias estructurales y funcionales del cerebro sinestésico, los hallazgos genéticos y los modelos explicativos. En la segunda parte se presentan tres estudios. En el primero de ellos (Capítulo II) se analiza la presencia de sinestesia en una muestra española para conocer la frecuencia relativa de sus diferentes modalidades. Los resultados han mostrado a) que la representación de la sinestesia en una muestra española de 803 personas es elevada (13,95%); b) que las sinestesias conceptuales son las más frecuentes; c) que la variable sinestesia es independiente de las variables sexo, edad, lateralidad manual y nivel educativo. Estos hallazgos sugieren que la sinestesia está presente en un elevado número de personas, especialmente cuando se trata de modalidades conceptuales, constatando la necesidad de considerar la variable sinestesia como un factor relevante en los diseños experimentales, y de proporcionar a los profesionales del ámbito clínico un adecuado conocimiento del fenómeno y sus características. En el segundo estudio (Capítulo III), se investigan las características estructurales del cerebro sinestésico grafema-color, mediante la combinación del análisis VBM de datos 3D-T1 y DTI, atendiendo a regiones corticales y subcorticales y explorando las bases neuroanatómicas del componente emocional del fenómeno. Este análisis ha confirmado que las diferencias anatómicas se encuentran distribuidas a nivel cortical y subcortical, incluyendo áreas relacionadas con el procesamiento emocional, lo que ha motivado la propuesta de un nuevo modelo explicativo ¿el Modelo de Integración Emocional. En el tercer estudio (Capítulo IV), se exploran las bases neurofuncionales de las sinestesias acromáticas, siendo esta la primera investigación que se ha centrado en este tipo de experiencias para comprender la sinestesia grafema-color, su dimensión emocional y el efecto de congruencia sinestésica. Los datos obtenidos han permitido confirmar a) que la base funcional de la sinestesia grafema-color se encuentra distribuída en el cerebro y refleja diferentes dimensiones de la experiencia sinestésica: un componente perceptivo, otro atencional/integrador y un componente emocional; b) que el color sinestésico y el color físico no poseen una base neural idéntica; y c) que el efecto de congruencia no debe ser utilizado como criterio para diferenciar la sinestesia congénita de las asociaciones adquiridas mediante aprendizaje asociativo por las personas neurotípicas. En la tercera y última parte Capítulo V, se presenta una discusión general que integra los resultados obtenidos en las tres investigaciones y se discuten las implicaciones que la aparición de este fenómeno tiene sobre el estudio de las diferencias individuales y el conocimiento de la cognición humana en general

DeepEye: Deep convolutional network for pupil detection in real environments

Robust identification and tracking of the pupil provides key information that can be used in several applications such as controlling gaze-based HMIs (human machine interfaces), designing new diagnostic tools for brain diseases, improving driver safety, detecting drowsiness, performing cognitive research, among others. We propose a deep convolutional neural network for eye-tracking based on atrous convolutions and spatial pyramids. DeepEye is able to handle real world problems such as varying illumination, blurring and reflections. The proposed network was trained and evaluated on 94,000 images taken from 24 data sets recorded in real world scenarios. DeepEye outperforms previous eye-tracking methods tested with these data sets. It improves the results of the current state of the art in a 26%, achieving an accuracy of more than 70% in almost every data set in terms of percentage of pupils detected with a distance error lower than 5 pixels.Depto. de Psicobiología y Metodología en Ciencias del ComportamientoFac. de PsicologíaTRUEpu