Traditional meditation, mindfulness and psychodynamic approach: An integrative perspective

The purpose of this article is to consolidate the inter-theoretical bridge between psychodynamic approach and TM, beyond the apparent incompatibility. Our impression is that even if some authors have already worked in order to fill the gap between TM and psychodynamic psychotherapy at theoretical level, this integration could be underrated and these efforts remain isolated. This could be due mainly to ambiguities in the translation of those terms with respect to the fundaments of core concepts of both perspectives, and a lack of empirical research on psychodynamic and meditation. Psychodynamic approach could embrace those aspects of TM that have been less developed in MBIs\u2019 theory and practice. Moreover, an integration of modern mindfulness practices into a psychodynamic framework should be explored. Further empirical studies and theoretical considerations are needed to corroborate testable hypotheses and comparing classical and combine

Memory NK cell features exploitable in anticancer immunotherapy

Besides their innate ability to rapidly produce effector cytokines and kill virus-infected or transformed cells, natural killer (NK) cells display a strong capability to adapt to environmental modifications and to differentiate into long-lived, hyperfunctional populations, dubbed memory or memory-like NK cells. Despite significant progress in the field of NK cell-based immunotherapies, some factors including their short life span and the occurrence of a tumor-dependent functional exhaustion have limited their clinical efficacy so that strategies aimed at overcoming these limitations represent one of the main current challenges in the field. In this scenario, the exploitation of NK cell memory may have a considerable potential. This article summarizes recent evidence in the literature on the peculiar features that render memory NK cells an attractive tool for antitumor immunotherapy, including their long-term survival and in vivo persistence, the resistance to tumor-dependent immunosuppressive microenvironment, the amplified functional responses to IgG-opsonized tumor cells, and in vitro expansion capability. Along with highlighting these issues, we speculate that memory NK cell-based adoptive immunotherapy settings would greatly take advantage from the combination with tumor-targeting therapeutic antibodies (mAbs), as a strategy to fully unleash their clinical efficacy

The words of the body: psychophysiological patterns in dissociative narratives

Trauma has severe consequences on both psychological and somatic levels, even affecting the genetic expression and the cell\u2019s DNA repair ability. A key mechanism in the understanding of clinical disorders deriving from trauma is identified in dissociation, as a primitive defense against the fragmentation of the self originated by overwhelming experiences. The dysregulation of the interpersonal patterns due to the traumatic experience and its detrimental effects on the body are supported by influent neuroscientific models such as Damasio\u2019s somatic markers and Porges\u2019 polyvagal theory. On the basis of these premises, and supported by our previous empirical observations on 40 simulated clinical sessions, we will discuss the longitudinal process of a brief psychodynamic psychotherapy (16 sessions, weekly frequency) with a patient who suffered a relational trauma. The research design consists of the collection of self-report and projective tests, pre-post therapy and after each clinical session, in order to assess personality, empathy, clinical alliance and clinical progress, along with the verbatim analysis of the transcripts trough the Psychotherapy Process Q-Set and the Collaborative Interactions Scale. Furthermore, we collected simultaneous psychophysiological measures of the therapeutic dyad: skin conductance and hearth rate. Lastly, we employed a computerized analysis of non-verbal behaviors to assess synchrony in posture and gestures. These automated measures are able to highlight moments of affective concordance and discordance, allowing for a deep understanding of the mutual regulations between the patient and the therapist. Preliminary results showed that psychophysiological changes in dyadic synchrony, observed in body movements, skin conductance and hearth rate, occurred within sessions during the discussion of traumatic experiences, with levels of attunement that changed in both therapist and the patient depending on the quality of the emotional representation of the experience. These results go in the direction of understanding the relational process in trauma therapy, using an integrative language in which both clinical and neurophysiological knowledge may take advantage of each other

Improving network formation in IEEE 802.15.4e DSME

Wireless Sensor and Actuator Networks are becoming attractive also for industrial applications, since recent standardization efforts have introduced significant improvement to reliability and deterministic communication delays. In this context, IEEE 802.15.4e is widely considered the major improvement, introducing many enhancements to the original IEEE 802.15.4 standard aimed at supporting critical applications. Among the new defined MAC protocols, Deterministic and Synchronous Multi-channel Extension (DSME) represents the most suitable option for applications with time-varying requirements. In this paper, an analysis of the IEEE 802.15.4 DSME MAC protocol during network formation is presented. The goal is to study the protocol performance and propose solutions to reduce the network formation time, improving energy and resource efficiency. To carry out the performance evaluation, DSME has been fully implemented in Contiki OS, an actual operating system for sensor nodes. The study has highlighted issues and inefficiencies in the network formation process, allowing to consequently propose effective solutions. In particular, it is proposed a set of guidelines for DSME configuration to the original MAC protocol that are proved to increase significantly the network formation efficiency

Obinutuzumab-mediated high-affinity ligation of FcγRIIIA/CD16 primes NK cells for IFNγ production

Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), based on the recognition of IgG-opsonized targets by the low-affinity receptor for IgG FcγRIIIA/CD16, represents one of the main mechanisms by which therapeutic antibodies (mAbs) mediate their antitumor effects. Besides ADCC, CD16 ligation also results in cytokine production, in particular, NK-derived IFNγ is endowed with a well-recognized role in the shaping of adaptive immune responses. Obinutuzumab is a glycoengineered anti-CD20 mAb with a modified crystallizable fragment (Fc) domain designed to increase the affinity for CD16 and consequently the killing of mAb-opsonized targets. However, the impact of CD16 ligation in optimized affinity conditions on NK functional program is not completely understood. Herein, we demonstrate that the interaction of NK cells with obinutuzumab-opsonized cells results in enhanced IFNγ production as compared with parental non-glycoengineered mAb or the reference molecule rituximab. We observed that affinity ligation conditions strictly correlate with the ability to induce CD16 down-modulation and lysosomal targeting of receptor-associated signaling elements. Indeed, a preferential degradation of FcεRIγ chain and Syk kinase was observed upon obinutuzumab stimulation independently from CD16-V158F polymorphism. Although the downregulation of FcεRIγ/Syk module leads to the impairment of cytotoxic function induced by NKp46 and NKp30 receptors, obinutuzumab-experienced cells exhibit an increased ability to produce IFNγ in response to different stimuli. These data highlight a relationship between CD16 aggregation conditions and the ability to promote a degradative pathway of CD16-coupled signaling elements associated to the shift of NK functional progra

Tumor-Targeting Anti-CD20 Antibodies Mediate In Vitro Expansion of Memory Natural Killer Cells: Impact of CD16 Affinity Ligation Conditions and In Vivo Priming

Natural Killer (NK) cells represent a pivotal player of innate anti-tumor immune responses. The impact of environmental factors in shaping the representativity of different NK cell subsets is increasingly appreciated. Human Cytomegalovirus (HCMV) infection profoundly affects NK cell compartment, as documented by the presence of a CD94/NKG2C+Fc∝RI≥- long-lived “memory” NK cell subset, endowed with enhanced CD16-dependent functional capabilities, in a fraction of HCMV seropositive subjects. However, the requirements for memory NK cell pool establishment/maintenance and activation have not been fully characterised yet. Here we describe the capability of anti-CD20 tumor-targeting therapeutic monoclonal antibodies (mAbs) to drive the selective in vitro expansion of memory NK cells, and we show the impact of donor' HCMV serostatus and CD16 affinity ligation conditions on this event. In vitro expanded memory NK cells maintain the phenotypic and functional signature of their freshly isolated counterpart; furthermore, our data demonstrate that CD16 affinity ligation conditions differently affect memory NK cell proliferation and functional activation, as rituximab-mediated low-affinity ligation represents a superior proliferative stimulus, while high-affinity aggregation mediated by glycoengineered obinutuzumab results in improved multifunctional responses. Our work also expands the molecular and functional characterization of memory NK cells, and investigates the possible impact of CD16 functional allelic variants on their in vivo and in vitro expansion. These results reveal new insights in Ab-driven memory NK cell responses in a therapeutic setting, and may ultimately inspire new NK cell-based intervention strategies against cancer, in which the enhanced responsiveness to mAb-bound target could significantly impact therapeutic efficacy

Tumor-associated and immunochemotherapy-dependent long-term alterations of the peripheral blood NK cell compartment in DLBCL patients

Natural Killer (NK) cells are a key component of tumor immunosurveillance and thus play an important role in rituximab-dependent killing of lymphoma cells via an antibody-dependent cellular cytotoxicity (ADCC) mechanism. We evaluated the phenotypic and functional assets of peripheral blood NK cell subsets in 32 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients and in 27 healthy controls. We further monitored long-term modifications of patient NK cells for up to 12 months after rituximab-based immunochemotherapy. At diagnosis, patients showed a higher percentage of CD56dim and CD16C NK cells, and a higher frequency of GrzBC cells in CD56dim, CD56bright, and CD16C NK cell subsets than healthy controls. Conversely, DLBCL NK cell killing and interferon g (IFNg) production capability were comparable to those derived from healthy subjects. Notably, NK cells from refractory/relapsed patients exhibited a lower “natural” cytotoxicity. A marked and prolonged therapy-induced reduction of both “natural” and CD16- dependent NK cytotoxic activities was accompanied by the down-modulation of CD16 and NKG2D activating receptors, particularly in the CD56dim subset. However, reduced NK cell killing was not associated with defective lytic granule content or IFNg production capability. This study firstly describes tumor-associated and therapy-induced alterations of the systemic NK cell compartment in DLBCL patients. As these alterations may negatively impact rituximab-based therapy efficacy, our work may provide useful information for improving immunochemotherapeutic strategies

Permeability-enhancing effects of three laurate-disaccharide monoesters across isolated rat intestinal mucosae

none8sìLaurate (C12)-sucrose esters are established intestinal epithelial permeation enhancers (PEs) with potential for use in oral delivery. Most studies have examined blends of ester rather than specific monoesters, with little variation on the sugar moiety. To investigate the influence of varying the sugar moiety on monoester performance, we compared three monoesters: C12-sucrose, C12-lactose, and C12-trehalose. The assays were: critical micellar concentration (CMC) in Krebs-Henseleit buffer, MTS and lactate dehydrogenase assays in Caco-2 cells, transepithelial electrical resistance (TEER) and apparent permeability coefficient (Papp) of [14C] mannitol across isolated rat intestinal mucosae, and tissue histology. For CMC, the rank order was C12-trehalose (0.21 mM) < C12-sucrose (0.34 mM) < C12-lactose (0.43 mM). Exposure to Caco-2 cells for 120 min produced TC50 values in the MTS assay from 0.1 to 0.4 mM. Each ester produced a concentration-dependent decrease in TEER across rat mucosae with 80% reduction seen with 8 mM in 5 min, but C12-trehalose was less potent. C12-sucrose and C12-lactose increased the Papp of [14C] mannitol across mucosae with similar potency and efficacy, whereas C12-trehalose was not as potent or efficacious, even though it still increased flux. In the presence of the three esters, gross intestinal histology was unaffected except at 8 mM for C12-sucrose and C12-lactose. In conclusion, the three esters enhanced permeability likely via tight junction modulation in rat intestinal tissue. C12-trehalose was not quite as efficacious, but neither did it damage tissue to the same extent. All three can be considered as potential PEs to be included in oral formulations.openMcCartney, Fiona; Perinelli, Diego R; Tiboni, Mattia; Cavanagh, Robert; Lucarini, Simone; Filippo Palmieri, Giovanni; Casettari, Luca; Brayden, David JMccartney, Fiona; Perinelli, Diego R; Tiboni, Mattia; Cavanagh, Robert; Lucarini, Simone; Filippo Palmieri, Giovanni; Casettari, Luca; Brayden, David

Prolactin variations during risperidone therapy in a sample of drug-naive children and adolescents

The aim of this prospective observational study was to investigate the variations of serum prolactin hormone (PRL) in a sample of 34 drug-naive patients (mean age 13 years) who started risperidone therapy assuming that several factors may favor the increase in serum PRL. Serum PRL and hyperprolactinemia clinical signs were examined at baseline (T0) and after almost 3 months of treatment (T1). We considered sex, pubertal status, risperidone dosage, psychiatric diagnosis, and any personal/family history of autoimmune diseases. The mean serum PRL value increased between T0 and T1 (P=0.004). The mean serum PRL was higher in females in the pubertal/postpubertal stage and for risperidone dosage up 1 mg/day. Hyperprolactinemia was found in 20% of patients at T0 and in 38% of patients at T1 (P=0.03). The mean serum PRL increase was greater in early-onset schizophrenia spectrum psychosis patients compared with no-early-onset schizophrenia spectrum psychosis patients (P=0.04). The increase in PRL was higher in patients with a personal and a family history of autoimmune diseases. This study suggests that the increase in serum PRL in patients treated with risperidone may be linked not only to the drug and its dosage but also to several risk factors such as sex, pubertal stage, psychiatric disease, and autoimmune disorders

Poetry in Pandemic: A Multimodal Neuroaesthetic Study on the Emotional Reaction to the Divina Commedia Poem

Poetry elicits emotions, and emotion is a fundamental component of human ontogeny. Although neuroaesthetics is a rapidly developing field of research, few studies focus on poetry, and none address its different modalities of fruition (MOF) of universal cultural heritage works, such as the Divina Commedia (DC) poem. Moreover, alexithymia (AX) resulted in being a psychological risk factor during the Covid-19 pandemic. The present study aims to investigate the emotional response to poetry excerpts from different cantica (Inferno, Purgatorio, Paradiso) of DC with the dual objective of assessing the impact of both the structure of the poem and MOF and that of the characteristics of the acting voice in experts and non-experts, also considering AX. Online emotion facial coding biosignal (BS) techniques, self-reported and psychometric measures were applied to 131 literary (LS) and scientific (SS) university students. BS results show that LS globally manifest more JOY than SS in both reading and listening MOF and more FEAR towards Inferno. Furthermore, LS and SS present different results regarding NEUTRAL emotion about acting voice. AX influences listening in NEUTRAL and SURPRISE expressions. DC’s structure affects DISGUST and SADNESS during listening, regardless of participant characteristics. PLEASANTNESS varies according to DC’s structure and the acting voice, as well as AROUSAL, which is also correlated with AX. Results are discussed in light of recent findings in affective neuroscience and neuroaesthetics, suggesting the critical role of poetry and listening in supporting human emotional processing