From autism to eating disorders and more: the role of oxytocin in neuropsychiatric disorders

Oxytocin (oxy) is a pituitary neuropeptide hormone synthesized from the paraventricular and supraoptic nuclei within the hypothalamus. Like other neuropeptides, oxy can modulate a wide range of neurotransmitter and neuromodulator activities. Additionally, through the neurohypophysis, oxy is secreted into the systemic circulation to act as a hormone, thereby influencing several body functions. Oxy plays a pivotal role in parturition, milk let-down and maternal behavior and has been demonstrated to be important in the formation of pair bonding between mother and infants as well as in mating pairs. Furthermore, oxy has been proven to play a key role in the regulation of several behaviors associated with neuropsychiatric disorders, including social interactions, social memory response to social stimuli, decision-making in the context of social interactions, feeding behavior, emotional reactivity, etc. An increasing body of evidence suggests that deregulations of the oxytocinergic system might be involved in the pathophysiology of certain neuropsychiatric disorders such as autism, eating disorders, schizophrenia, mood, and anxiety disorders. The potential use of oxy in these mental health disorders is attracting growing interest since numerous beneficial properties are ascribed to this neuropeptide. The present manuscript will review the existing findings on the role played by oxy in a variety of distinct physiological and behavioral functions (Figure 1) and on its role and impact in different psychiatric disorders. The aim of this review is to highlight the need of further investigations on this target that might contribute to the development of novel more efficacious therapies. Figure 1Oxytocin regulatory control of different and complex processes

Web Health Monitoring Survey: a new approach to enhance effectiveness of telemedicine systems

Aging of the European population and interest in a healthy population in western countries have contributed to an increase in the number of health surveys, where the role of survey design, data collection, and data analysis methodology is clear and recognized by the whole scientific community. Survey methodology has had to couple with the challenges deriving from data collection through information and communications technology (ICT). Telemedicine systems have not used patients as a source of information, often limiting them to collecting only biometric data. A more effective telemonitoring system would be able to collect objective and subjective data (biometric parameters and symptoms reported by the patients themselves), and to control the quality of subjective data collected: this goal be achieved only by using and merging competencies from both survey methodology and health research. The objective of our study was to propose new metrics to control the quality of data, along with the well-known indicators of survey methodology. Web questionnaires administered daily to a group of patients for an extended length of time are a Web health monitoring survey (WHMS) in a telemedicine system. We calculated indicators based on paradata collected during a WHMS study involving 12 patients, who signed in to the website daily for 2 months. The patients’ involvement was very high: the patients’ response rate ranged between 1.00 and 0.82, with an outlier of 0.65. Item nonresponse rate was very low, ranging between 0.0% and 7.4%. We propose adherence to the chosen time to connect to the website as a measure of involvement and cooperation by the patients: the difference from the median time ranged between 11 and 24 minutes, demonstrating very good cooperation and involvement from all patients. To measure habituation to the questionnaire, we also compared nonresponse rates to the items between the first and the second month of the study, and found no significant difference. We computed the time to complete the questionnaire both as a measure of possible burden for patient, and to detect the risk of automatic responses. Neither of these hypothesis was confirmed, and differences in time to completion seemed to depend on health conditions. Focus groups with patients confirmed their appreciation for this “new” active role in a telemonitoring system. The main and innovative aspect of our proposal is the use of a Web questionnaire to virtually recreate a checkup visit, integrating subjective (patient’s information) with objective data (biometric information). Our results, although preliminary and if need of further study, appear promising in proposing more effective telemedicine systems. Survey methodology could have an effective role in this growing field of research and applications

Surveys as Praxis: A Pilot Study on Transformative Learning Assessment with the Laboratory Experience of the Theatre of the Oppressed

Transformative learning has been important in the development of college and adult education since Jack Mezirow proposed it more than 40 years ago as a theoretical description of the steps learners undergo in changing their worldviews. From the educator’s perspective, transformative learning is when a learner is struck by a new concept or way of thinking and then follows through to make a life change; it supplements more common types of learning such as acquiring facts or learning new skills (Cranton, 2006) [1]. Little quantitative study has been made of the incidence of transformative learning or the ten steps predicted by Mezirow to precede it (Taylor, 2007) [2]. More European involvement in research on transformative learning is needed, given that the theory of transformative learning does not have concrete roots in the conceptual formation of the European adult educators (Kokkos, 2012) [3]. European adult educators’ rich scholarship on the social and critical dimensions of adult learning (Bourdieu, Foucault, Mayo) would have much to offer the study of transformative learning theory (Taylor & Cranton, 2013) [4]. The real innovation could be the reintegration of the transformative learning with ideas, theories and methodologies of freirerian pedagogy and of democratic adult education, such as Theatre of Oppressed and Forum Theatre, derived from the theory of Augusto Boal (2005) [5]. Our purpose is to create a collaborative international research to study the processes of transformative learning occurring during university laboratory experiences based on Freire’s pedagogical tools and on Boal’s Forum Theatre and Theatre of the Oppressed with graduating students. This paper presents the international pilot study for the validation of the instrument for assessment of the transformative learning adopting the perspective of the theory of ten precursor steps (Taylor, 2007; Brock, 2011) [6]

Investigating the role of the central melanocortin system in stress and stress-related disorders

The melanocortinergic neural circuit, known for its influence on energy expenditure and feeding behavior, also plays a role in stress and stress-induced psychiatric disorders, including anxiety and depression. The major contribution is given by the melanocortin-4 receptor (MC4R) subtype, highly expressed in brain regions involved in the control of stress responses. Furthermore, the MC4R appears to profoundly affect the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and it has been also highlighted a functional and anatomical interaction with the corticotropin-releasing factor (CRF), an important mediator of stress and stress-related behaviors. The MC4R agonists seem to exacerbate stress-inducing anxiety- and depressive-like behavior, while MC4R antagonists have been demonstrated to mitigate such disorders, as shown in several preclinical behavioral tests. The evidence collected in the present review suggests that the melanocortin system, through the MC4R, could possibly modulate behavioral responses to stress, suggesting the use of MC4R antagonists as a possible novel treatment for anxiety and depression induced by stress

Anxiety associated with palatable food withdrawal is reversed by the selective FAAH inhibitor PF-3845: A regional analysis of the contribution of endocannabinoid signaling machinery

Objective: Consumption of energy-dense palatable "comfort" food can alleviate stress and negative emotions, while abrupt withdrawal from a palatable diet can worsen these symptoms, causing difficulties with adherence to weight-loss diets. Currently, no pharmacological treatment is effective for obesity-related anxiety, so we investigated the endocannabinoid system (ECS), and specifically the fatty acid amide hydrolase (FAAH), as an interesting emerging target in this context because of its key role in the regulation of both energy homeostasis and emotional behavior. Methods: Rats were subjected to exposure and subsequent abstinence from a palatable cafeteria diet. During abstinence period, rats were treated with the selective FAAH inhibitor PF-3845 (10 mg/kg; intraperitoneal administration every other day). Results: Abstinent rats displayed an anxiogenic-like behavior and changes in the proteins of ECS signaling machinery in brain areas involved both in anxiety and food intake regulation. In particular, withdrawal caused a reduction of the expression of cannabinoid receptors in the nucleus accumbens and of enzymes diacylglycerol lipase alpha and monoacylglycerol lipase (MAGL) in the amygdala. Pharmacological inhibition of FAAH exerted an anxiolytic-like effect in abstinent animals and increased both MAGL expression in amygdala and CB2 expression in prefrontal cortex. Discussion: Overall, our results suggest that emotional disturbances associated with dieting are coupled with region-specific alterations in the cerebral expression of the ECS and that the enhancement of the endocannabinoid signaling by FAAH inhibition might represent a novel pharmacological strategy for the treatment of anxiety related to abstinence from palatable food.Funding for open access charge: Universidad de Málaga / CBUA European Regional DevelopmentFunds-European Union, Grant/Award Number:PI19/01577; Instituto de Salud Carlos III,Grant/Award Number: RETICS; Ministerio deCiencia e Innovaci on, Grant/Award Number:ERDF-EU RD16/0017/0001; Ministerodell'Università e della Ricerca, Grant/AwardNumber: 2012JTX3KL; PNRR-RomeTechnopole-FP

Anxiety associated with palatable food withdrawal is reversed by the selective FAAH inhibitor PF-3845: A regional analysis of the contribution of endocannabinoid signaling machinery

ObjectiveConsumption of energy-dense palatable "comfort" food can alleviate stress and negative emotions, while abrupt withdrawal from a palatable diet can worsen these symptoms, causing difficulties with adherence to weight-loss diets. Currently, no pharmacological treatment is effective for obesity-related anxiety, so we investigated the endocannabinoid system (ECS), and specifically the fatty acid amide hydrolase (FAAH), as an interesting emerging target in this context because of its key role in the regulation of both energy homeostasis and emotional behavior. MethodsRats were subjected to exposure and subsequent abstinence from a palatable cafeteria diet. During abstinence period, rats were treated with the selective FAAH inhibitor PF-3845 (10 mg/kg; intraperitoneal administration every other day). ResultsAbstinent rats displayed an anxiogenic-like behavior and changes in the proteins of ECS signaling machinery in brain areas involved both in anxiety and food intake regulation. In particular, withdrawal caused a reduction of the expression of cannabinoid receptors in the nucleus accumbens and of enzymes diacylglycerol lipase alpha and monoacylglycerol lipase (MAGL) in the amygdala. Pharmacological inhibition of FAAH exerted an anxiolytic-like effect in abstinent animals and increased both MAGL expression in amygdala and CB2 expression in prefrontal cortex. DiscussionOverall, our results suggest that emotional disturbances associated with dieting are coupled with region-specific alterations in the cerebral expression of the ECS and that the enhancement of the endocannabinoid signaling by FAAH inhibition might represent a novel pharmacological strategy for the treatment of anxiety related to abstinence from palatable food. Public SignificanceThe present study focused on evaluating the role of the endocannabinoid system in modulating withdrawal from naturally rewarding activities that have an impact on mood, such as feeding. The variations observed in the emotional behavior of abstinent rats was linked to neuroadaptations of the ECS in specific brain areas

Lack of efficacy of convalescent plasma in COVID-19 patients with concomitant hematological malignancies: An Italian retrospective study

A multicenter retrospective study was designed to assess clinical outcome of COVID-19 in patients with hematological malignancies (HM) following treatment with anti-SARS-CoV-2 convalescent plasma (CP) or standard of care therapy. To this aim, a propensity score matching was used to assess the role of non-randomized administration of CP in this high-risk cohort of patients from the Italian Hematology Alliance on COVID-19 (ITA-HEMA-COV) project, now including 2049 untreated control patients. We investigated 30- and 90-day mortality, rate of admission to intensive care unit, proportion of patients requiring mechanical ventilatory support, hospitalization time, and SARS-CoV-2 clearance in 79 CP recipients and compared results with 158 propensity score-matched controls. Results indicated a lack of efficacy of CP in the study group compared with the untreated group, thus confirming the negative results obtained from randomized studies in immunocompetent individuals with COVID-19. In conclusion, this retrospective analysis did not meet the primary and secondary end points in any category of immunocompromized patients affected by HM

Generation and Characterization of a Tumor Stromal Microenvironment and Analysis of Its Interplay with Breast Cancer Cells: An In Vitro Model to Study Breast Cancer-Associated Fibroblast Inactivation

Breast cancer-associated fibroblasts (BCAFs), the most abundant non-cancer stromal cells of the breast tumor microenvironment (TME), dramatically sustain breast cancer (BC) progression by interacting with BC cells. BCAFs, as well as myofibroblasts, display an up regulation of activation and inflammation markers represented by α-smooth muscle actin (α-SMA) and cyclooxygenase 2 (COX-2). BCAF aggregates have been identified in the peripheral blood of metastatic BC patients. We generated an in vitro stromal model consisting of human primary BCAFs grown as monolayers or 3D cell aggregates, namely spheroids and reverted BCAFs, obtained from BCAF spheroids reverted to 2D cell adhesion growth after 216 h of 3D culture. We firstly evaluated the state of activation and inflammation and the mesenchymal status of the BCAF monolayers, BCAF spheroids and reverted BCAFs. Then, we analyzed the MCF-7 cell viability and migration following treatment with conditioned media from the different BCAF cultures. After 216 h of 3D culture, the BCAFs acquired an inactivated phenotype, associated with a significant reduction in α-SMA and COX-2 protein expression. The deactivation of the BCAF spheroids at 216 h was further confirmed by the cytostatic effect exerted by their conditioned medium on MCF-7 cells. Interestingly, the reverted BCAFs also retained a less activated phenotype as indicated by α-SMA protein expression reduction. Furthermore, the reverted BCAFs exhibited a reduced pro-tumor phenotype as indicated by the anti-migratory effect exerted by their conditioned medium on MCF-7 cells. The deactivation of BCAFs without drug treatment is possible and leads to a reduced capability of BCAFs to sustain BC progression in vitro. Consequently, this study could be a starting point to develop new therapeutic strategies targeting BCAFs and their interactions with cancer cells

VIII Concurso Internacional de Canto Francisco Viñas : concierto final

Programa de la vuitena edició del Concurs Internacional de Cant Francesc Viñas, que va tenir lloc a Barcelona entre el 14 i el 22 de novembre de 1970. Hi va participar l'Orquestra Simfònica del Gran Teatre del Liceu sota la direcció de R. Bottino. Hi van participar J. Thomas, J. R. Puigbó, M. Romero Sangalli, G. Kershhakl, I. Rocha, G. Savova, G. Takova. U. Withen, I. Aragón, I. Burgos, M. E. Guarro, O. Gutiérrez, M. Hernández, M. C. Herrera, J. Poch, A. Barasorda, J. Barry, M. Canning, A. Peters, L. Smart, R. Turner, A. Valentín, L-V. Williams, C. Duprat, R. Franc, Y. Perrin, M. Solari, R. Van der Meer, R. Ferguson, P. Taylor, A. Murray, R. Bruni, L. Canepa, F. Piantanida, M. V. Romano, A. M. Viglione, M. Ara, S. Minemura, H. Ochiai, M. Saito, Y. Sue, S. Tahara, T. Tsunemori, T. Sunemori, U. Borzdynska, M. Cononovici G. Crasnaru, E. Duma, A. Farcas, D. Musetescu, V. Pop-Ivan, G. Radler Spireanu, R. Vlad, E. Zarnescu, E. Obrastsova, S. Sotkilava, C. Báez-Finol, R. Reyna, Y. RuizEl jurat estava compost per R. Vuataz, C. A. Pizzini, C. Badia, K. Borg, J. M. Colomer Pujol, Y. Le Marc-Hadour, J. Micheau, G. Moore, E. Nuñez, J. Pich Santasusana, L. Prats. S'hi van interpretar fragments de "Les Noces de Figaro" de W. A. Mozart, "Andrea Chénier" de M. Gioradno, "Don Carlo" de G. Verdi, "La Bohème" de G. Puccini, "La Profetisa" d'H. Purcell, "La vague et la cloche" d'H. Duparc, "Tannhäuser" de R. Wagner, "Faust" de C. Gounod, "Samson i Dalila" de C. Saint-Saens i de "Carmen" de G. Bizet. També s'hi va sentir "Mai" de Fauré, "Kennst du das Land?" d'H. Wolf, "Liebesbotschaft" de F. SchubertOrquestra Simfònica del Gran Teatre del Liceu dirigida per Riccardo BottinoDe cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents