Chemotherapy-Induced Tumor Cell Death at the Crossroads Between Immunogenicity and Immunotolerance: Focus on Acute Myeloid Leukemia

In solid tumors and hematological malignancies, including acute myeloid leukemia, some chemotherapeutic agents, such as anthracyclines, have proven to activate an immune response via dendritic cell-based cross-priming of anti-tumor T lymphocytes. This process, known as immunogenic cell death, is characterized by a variety of tumor cell modifications, i.e., cell surface translocation of calreticulin, extracellular release of adenosine triphosphate and pro-inflammatory factors, such as high mobility group box 1 proteins. However, in addition to with immunogenic cell death, chemotherapy is known to induce inflammatory modifications within the tumor microenvironment, which may also elicit immunosuppressive pathways. In particular, DCs may be driven to acquire tolerogenic features, such as the overexpression of indoleamine 2,3-dioxygensase 1, which may ultimately hamper anti-tumor T-cells via the induction of T regulatory cells. The aim of this review is to summarize the current knowledge about the mechanisms and effects by which chemotherapy results in both activation and suppression of anti-tumor immune response. Indeed, a better understanding of the whole process underlying chemotherapy-induced alterations of the immunological tumor microenvironment has important clinical implications to fully exploit the immunogenic potential of anti-leukemia agents and tune their application

EEG-informed fMRI analysis during a hand grip task: estimating the relationship between EEG rhythms and the BOLD signal.

In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neural activity, rather than with absolute power. Concurrently, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be also important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between the two signals. Here we propose a method to perform EEG-informed fMRI analysis where the changes in the spectral profile are modeled, and, at the same time, the distinction between rhythms is preserved. We compared our model with two other frequency-dependent regressors modeling using simultaneous EEG-fMRI data from healthy subjects performing a motor task. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related, well localized activated volumes. Furthermore, we showed that including among the regressors also EEG rhythms not primarily involved in the task enhances the performance of the analysis, even when only correlations with BOLD signal and specific EEG rhythms are explore

Control de la hipertensión arterial por especialistas en Argentina (estudio charter)

Introducción: La proporción de hipertensos medicados que presentan adecuado control de su HTA es muy baja a nivel mundial, del orden del 32,5%. Objetivos: 1)determinar el grado de control de la HTA en hipertensos medicados, tratados en centros especializados de la República Argentina; 2) caracterizar a los pacientes atendidos en dichos centros respecto de su perfil de riesgo cardiovascular; analizar el número y tipo de antihipertensivos utilizados; determinar los factores asociados a un adecuado control de la presión arterial(PA). Metodología: estudio de corte transversal, en el que se incluyeron mayores de 18 años con diagnóstico establecido de hipertensión arterial, bajo tratamiento farmacológico, provenientes de 10 centros de referencia en HTA de la Argentina. En una única visita se midió la PA [3 lecturas] y se registraron variables antropométricas y demográficas, así como las características del tratamiento antihipertensivo. Se consideró adecuado control de la PA en consultorio a un promedio por debajo de 140/90 mmHg en 80 años. Se estimó el porcentaje del grado de control de la PA con su IC95% y se determinaron las variables independientemente asociadas con el adecuado control de la PA a través de un análisis de regresión logística multivariable. Resultados: se incluyeron 1146 pacientes. El promedio de edad fue de 63,5 (13,1) años, 42,8% varones, 19,7% diabéticos, 8,3% tabaquistas, 67,4% dislipidémicos, 8,1% con antecedentes de enfermedad coronaria y 6,7% con antecedentes de enfermedad cerebrovascular. La media de PA en consultorio fue de 135,3 (14,8)/ 80,8 (10) mmHg, siendo el porcentaje de adecuado control de la PA de 64,8% (IC95%: 62-67,6%). El consumo promedio de antihipertensivos fue de 2,1 (1) drogas por paciente (Figura 1). En la Tabla 1 se muestran las características de los sujetos con adecuado vs. inadecuado control de la PA. En el análisis multivariable, sólo el sexo femenino fue un predictor independiente de adecuado control (OR 1,33 [IC95% 1,02-1,72],p=0,04). Conclusiones: un 65% de los pacientes hipertensos tratados en centros especializados de la Argentina presentan adecuado control de PA, siendo esta cifra muy superior a la reportada en población general. Futuros estudios deberán definir estrategias para optimizar el control en centros no especializados.Fil: Marin, Marcos. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Barochiner, Jessica. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Rodriguez, Pablo. Instituto Cardiovascular de Buenos Aires; ArgentinaFil: Renna, Nicolas Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; ArgentinaFil: Castellaro, Carlos. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Espeche, Walter. Universidad Nacional de La Plata; ArgentinaFil: De Cerchio, Alejandro. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Del Sueldo, Mildren. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Visani, Sergio. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Zilberman, Judith. Sociedad Argentina de Hipertensión Arterial; ArgentinaXXVI Congreso Argentino de Hipertensión ArterialMar del PlataArgentinaSociedad Argentina de Hipertensión Arteria

Spectral and Bispectral Analysis of the EEG Rhythms in Basal Conditions and During Photic Stimulation

The aim of the present study is the quantification of the relationships and the phase coupling among spectral peaks in the EEG signal at different sites of the scalp. 10 normal subjects underwent the study. The multi-channel EEG signal was recorded during basal conditions and during photic stimulation. The stimulation frequency (SF) has been chosen related to the single subject's spontaneous alpha rhythm (SF = /spl alpha/, SF = 2/spl alpha/, SF = /spl alpha//2) and not related to the /spl alpha/ rhythm (SF = 14 Hz). Spectral and bispectral analysis put into evidence that, in basal conditions, with closed eyes, the spontaneous /spl alpha/ rhythm is generated by independent oscillators in the occipital and frontal regions. In addition the /spl beta/ rhythm in the spectra seems an harmonic component linked to the former one. During photic stimulation the spontaneous /spl alpha/ rhythm is drastically decreased, and the harmonics are lowered, while frontal and occipital responses seem to synchronize. In addition the frontal lobe seems able to generate sub-harmonics which could be related to the genesis of generalized seizures in predisposed subjects

EEG-informed fMRI analysis during a hand grip task

In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neuronal activity, rather than with absolute neural power. On the other hand, though, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between EEG and BOLD. Here we proposed a novel method to perform EEG-informed fMRI analysis, so that the EEG regressors take into account both the changes in the spectral profile and the rhythms distinction. We applied it to EEG-fMRI data during a bimanual motor task in healthy subjects, and compared the results with those obtained by regressing fMRI data onto a single regressor covering the entire range of frequencies, ignoring the distinction between different EEG rhythms. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related well localized activated volumes

EEG-informed fMRI analysis during a hand grip task: estimating the relationship between EEG rhythms and the BOLD signal

In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neural activity, rather than with absolute power. Concurrently, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be also important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between the two signals. Here we propose a method to perform EEG-informed fMRI analysis where the changes in the spectral profile are modeled, and, at the same time, the distinction between rhythms is preserved. We compared our model with two other frequency-dependent regressors modeling using simultaneous EEG-fMRI data from healthy subjects performing a motor task. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related, well localized activated volumes. Furthermore, we showed that including among the regressors also EEG rhythms not primarily involved in the task enhances the performance of the analysis, even when only correlations with BOLD signal and specific EEG rhythms are explored