Tumor-derived exosomes favor immunosuppression and metastatic spread by acting on myeloid cells

It is widely recognized that the immune system can be highly affected by tumors through a plethora of mechanisms that allow avoiding an efficient recognition and eradication of cancer cells. Among these mechanisms, tumor secretome, including tumor-derived soluble factors (TDSFs) and, more recently, extracellular vesicles (EVs), is currently drawing much attention in the immune-oncology field. Particularly, by interacting either with stromal or other tumor cells, tumor-derived exosomes (TEX) have been demonstrated as key regulators in cancer development, as well as on the metastatic process. Since myeloid-derived suppressor cells (MDSCs) are critical contributors to the aforementioned processes, we investigated the TEX-MDSCs interaction, highlighting the main functional consequences of this crosstalk. Indeed, we could demonstrate a TEX-mediated effect on MDSC suppressive functions, which was even more striking in the case of bone-marrow na\uefve monocytes. Furthermore, we demonstrated that this is mainly mediated by iNOS engagement on myeloid cells, possibly induced by molecules enriched within TEX. In addition, the injection of TEX derived from high metastatic cancer cells in na\uefve tumor-free mice before the tumor challenge with a low metastatic cell line induced an increased spread of cancer cells in the lungs of TEX-treated mice. In the attempt to dampen TEX detrimental effects in tumor models, we blocked exosome secretion through GW4869 drug administration, which did not ameliorate the spread of metastatic cells. On the contrary, by targeting one of the TEX-downstream mediators, i.e. a member of the S100 proteins family, tumor-bearing mice displayed a restrained suppressive tumor network and a strong reduction in the metastatic incidence. Finally, we demonstrated that S100A8/A9 sera levels negatively correlated with distant metastasis-free survival in pancreatic ductal adenocarcinoma (PDAC) patients. In conclusion, our preliminary data highlighted the urgency of developing novel and more effective therapeutic approaches based on a full characterization of TEX-induced pathways in myeloid cells within the local tumor milieu and, moreover, at distal sites of metastasis

True and false DRM memories: differences detected with an implicit task

Memory is prone to illusions. When people are presented with lists of words associated with a non-presented critical lure, they produce a high level of false recognitions (false memories) for non-presented related stimuli indistinguishable, at the explicit level, from presented words (DRM paradigm). We assessed whether true and false DRM memories can be distinguished at the implicit level by using the autobiographical IAT (aIAT), a novel method based on indirect measures that permits to detect true autobiographical events encoded in the respondent's mind/brain. In our experiment, after a DRM task participants performed two aIATs: the first aimed at testing implicit memory for presented words (true-memories aIAT) and the second aimed at evaluating implicit memory for critical lures (false-memories aIAT). Specifically, the two aIATs assessed the association of presented words and critical lures with the logical dimension "true." Results showed that the aIAT detected a greater association of presented words than critical lures with the logical dimension "true."This result indicates that although true and false DRM memories are indistinguishable at the explicit level a different association of the true and false DRM memories with the logical dimension "true" can be detected at the implicit level, and suggests that the aIAT may be a sensitive instrument to detect differences between true and false DRM memories. © 2012 Marini, Agosta, Mazzoni, Dalla Barba and Sartori

Enhancing critical thinking skills and media literacy in initial VET students: a mixed methods study on a cross-country training program

Context: In the last few decades, the constant and exponential changes in the society\u27s consumption of information have increased the awareness of practitioners from the education and training field, on the need for training programs for the enhancement of critical thinking skills and media literacy among students from Initial Vocational Education and Training (IVET) who are less exposed to intellectual trainings than their peers in traditional education pathways. Approach: With this impetus, the present paper reports the results of a mixed methods study evaluating a training program for such competences. Based on a cognitive psychology theoretical framework, the training program consisted in three main techniques through which trainers can work with students in the classroom. N= 35 trainers from five different countries (i.e., Greece, Italy, Spain, Portugal, and the Netherlands) were instructed about the training techniques and implemented them in their training centres. Then, a total of N= 288 students among these countries were involved in the testing of the training, which took place on a duration average of 5 months. Mixed methods approach was used to evaluate the effectiveness and quality of the training. Notably, prospective statistical analysis evaluated the training\u27s impact of the participating students and compared with a control group. Qualitative interviews examined the training\u27s lived experience with a group of students and trainers. Findings: The quantitative and qualitative analysis of pre/post- measures of critical thinking skills and media literacy of the experimental group, and the comparison with the control group, indicate an increase in these competences and confirm the efficacy of the training intervention. Conclusion: These results inform about the usefulness of the training program cross-culturally and the feasibility of training strategies based on cognitive psychology. Moreover, the paper offers a methodological contribution thanks to the proposition of the mixed methods approach for training programs assessment. (DIPF/Orig.

Assessing the effects of tDCS over a delayed response inhibition task by targeting the right inferior frontal gyrus and right dorsolateral prefrontal cortex

Many situations in our everyday life call for a mechanism deputed to outright stop an ongoing course of action. This behavioral inhibition ability, known as response stopping, is often impaired in psychiatric conditions characterized by impulsivity and poor inhibitory control. Transcranial direct current stimulation (tDCS) has recently been proposed as a tool for modulating response stopping in such clinical populations, and previous studies in healthy humans have already shown that this noninvasive brain stimulation technique is effectively able to improve response stopping, as measured in a stop-signal task (SST) administered immediately after the stimulation. So far, the right inferior frontal gyrus (rIFG) has been the main focus of these attempts to modulate response stopping by the means of noninvasive brain stimulation. However, other cortical areas such as the right dorsolateral prefrontal cortex (rDLPFC) have been implicated in inhibitory control with other paradigms. In order to provide new insight about the involvement of these areas in response stopping, in the present study, tDCS was delivered to 115 healthy subjects, using five stimulation setups that differed in terms of target area (rIFG or rDLPFC) and polarity of stimulation (anodal, cathodal, or sham). The SST was performed 15 min after the offset of the stimulation. Consistently with previous studies, only anodal stimulation over rIFG induced a reliable, although weak, improvement in the SST, which was specific for response stopping, as it was not mirrored in more general reaction time measures

Enhancing Critical Thinking Skills and Media Literacy in Initial VET Students: A Mixed Methods Study on a Cross-Country Training Program

Context: In the last few decades, the constant and exponential changes in the society's con-sumption of information have increased the awareness of practitioners from the education and training field, on the need for training programs for the enhancement of critical thin-king skills and media literacy among students from Initial Vocational Education and Trai-ning (IVET) who are less exposed to intellectual trainings than their peers in traditional education pathways.Approach: With this impetus, the present paper reports the results of a mixed methods study evaluating a training program for such competences. Based on a cognitive psychology theoretical framework, the training program consisted in three main techniques through which trainers can work with students in the classroom. N= 35 trainers from five different countries (i.e., Greece, Italy, Spain, Portugal, and the Netherlands) were instructed about the training techniques and implemented them in their training centres. Then, a total of N= 288 students among these countries were involved in the testing of the training, which took place on a duration average of 5 months. Mixed methods approach was used to eva-luate the effectiveness and quality of the training. Notably, prospective statistical analysis evaluated the training's impact of the participating students and compared with a control group. Qualitative interviews examined the training's lived experience with a group of stu-dents and trainers

Transcranial direct current stimulation and cognitive training in the rehabilitation of Alzheimer disease: A case study

In the present study we tested the cognitive effects of transcranial direct current stimulation (tDCS) in a case of probable Alzheimer disease (AD). The patient (male, 60 years, mild AD) underwent two cycles of treatments, separated by 2 months. In the first cycle, active stimulation (10 sessions, 2 mA for 20 min; anode over the left dorsolateral prefrontal cortex) was followed by computerised tasks (CTs) specifically chosen to engage the most impaired cognitive processes in the patient (tDCS+CT condition). In the second cycle, which was structured as the first, CTs were administered after placebo stimulation (sham+CT condition). Effects on cognitive performance were evaluated not only by the CTs, but also by neuropsychological tests assessing global cognitive functioning. Statistical analyses revealed that whereas the tDCS+CT condition had few effects on the CTs, it induced a stability of the patient\u2019s global cognitive functioning lasting approximately 3 months, which was not achieved when the patient underwent sham+CT condition. Therefore, the synergetic use of tDCS and CTs appeared to slow down the cognitive decline of our patient.This preliminary result, although in need of further confirmation, suggests the potentiality of tDCS as an adjuvant tool for cognitive rehabilitation in AD

Validation of an enhanced recovery after surgery protocol in gynecologic surgery: an Italian randomized study

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Early putamen hypertrophy and ongoing hippocampus atrophy predict cognitive performance in the first ten years of relapsing-remitting multiple sclerosis

Background The first years of relapsing-remitting multiple sclerosis (RRMS) constitute the most vulnerable phase for the progression of cognitive impairment (CImp), due to a gradual decrease of compensatory mechanisms. In the first 10 years of RRMS, the temporal volumetric changes of deep gray matter structures must be clarified, since they could constitute reliable cognitive biomarkers for diagnostic, prognostic, and therapeutic purposes. Methods Forty-five cognitively asymptomatic patients with RRMS lasting 64\u200910 years, and with a brain MRI performed in a year from the neuropsychological evaluation (Te-MRI), were included. They performed the Brief International Cognitive Assessment battery for MS. Thirty-one brain MRIs performed in the year of diagnosis (Td-MRI) and 13 brain MRIs of age- and sex-matched healthy controls (HCs) were also included in the study. The relationships between clinical features, cognitive performances, and Te- and Td-MRI volumes were statistically analyzed. Results Cognitively preserved (CP) patients had significantly increased Td-L-putamen (P\u2009=\u20090.035) and Td-R-putamen volume (P\u2009=\u20090.027) with respect to cognitively impaired (CI) ones. CI patients had significantly reduced Te-L-hippocampus (P\u2009=\u20090.019) and Te-R-hippocampus volume (P\u2009=\u20090.042) compared, respectively, with Td-L-hippocampus and Td-R-hippocampus volume. Td-L-putamen volume (P\u2009=\u20090.011) and Te-L-hippocampus volume (P\u2009=\u20090.023) were independent predictors of the Symbol Digit Modalities Test score in all patients (r2\u2009=\u20090.31, F\u2009=\u20096.175, P\u2009=\u20090.001). Conclusion In the first years of RRMS, putamen hypertrophy and hippocampus atrophy could represent promising indices of cognitive performance and reserve, and become potentially useful tools for diagnostic, prognostic, and therapeutic purposes

Repensando las Familias: Aproximaciones históricas, miradas interdisciplinarias

¿Para qué estudiar la familia? ¿Qué pueden aportar los estudios de familia a las Ciencias Sociales y Humanas? Estos son algunos de los interrogantes sobre los que se pretende reflexionar a lo largo de estas páginas. Entre las potencialidades que resaltan al momento de indagar sobre este objeto de estudio que constituye lo familiar, destaca la interdisciplina. Variedad de categorías analíticas, préstamos conceptuales, pluralidad de miradas, líneas de investigación, metodologías y fuentes proponen múltiples posibilidades para su conocimiento. Entendemos que la familia constituye un objeto privilegiado y poderoso como vía de ingreso para el conocimiento de la sociedad, tanto en referencia al universo de lo público, en su intervinculación con los poderes hegemónicos, así como respecto de sus lazos con la realidad doméstica y cotidiana. Entre las líneas de investigación desarrolladas en el Programa Estructuras y Estrategias Familiares de Ayer y de Hoy se presentan en este espacio, a modo de ejercicio ejemplificativo y desde lo sociocultural, algunas miradas de investigación.What is the purpose of studying family? What can family studies provide to Social and Human Sciences? These are some of the questions on which we seek to reflect over these pages. Among the posibilities that highlight when inquiring about this object of study, the interdisciplinary stands out. Variety of analytical categories, conceptual exchanges, plurality of looks, lines of research, methodologies and sources suggest many possibilities for its knowledge. We understand that the family is a privileged and powerful object as entrance to the study of society, both in reference to the universe of the public, in their interlinking with hegemonic powers, and about their links with domestic and quotidian reality. In this article we present an example of some of the research lines that are developed in the Program Estructuras y Estrategias Familiares de Ayer y de Hoy.Fil: Moyano, Sara Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; ArgentinaFil: Sartori Moyano, Federico Tulio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; ArgentinaFil: Moreyra, Cecilia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; Argentin