A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication

The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension

"Just before": intimate partner violence: rappresentazioni e nuovi focus per il trattamento

La violenza contro le donne rappresenta un fenomeno altamente complesso e muldimensionale, ampiamente trasversale ed esteso sia a livello nazionale che internazionale. La sua forma più diffusa, la Intimate Partner Violence (IPV) – Violenza da partner intimo, nei contesti familiari, diventa purtroppo causa di sofferenza estrema e violenza assistita (Witnessed Violence – WV). Il modello offre una linea di lettura e intervento che ne rispetta la multidimensionalità, ma pone di fronte alla necessità di integrare i vari livelli e metterli a dialogo, soprattutto a livello operativo. Rivolgendo l'attenzione ai setting di intervento preventivo e/o emergenziale, e alla prospettiva maschile, ancora troppo ambigua e frammentaria nella mente di chi lavora nei servizi, la presente ricerca si pone l'obiettivo di stilare delle linee guida operative e olistiche per la prevenzione e la presa in carico dei casi di IPV, che possano fungere da riferimento nei percorsi di formazione di chi opera nei servizi di welfare, dirigendo un processo di cambiamento dello status quo dei servizi dedicati e non. La ricerca è stata condotta attraverso 2 studi: il primo con 50 operatori/trici (45 donne e 5 uomini) che lavorano nei servizi di welfare locale e il secondo con 37 uomini che si sono resi disponibili alla sperimentazione del ViDaCS serious game. Nel primo studio è stata utilizzata una Intervista Narrativa Focalizzata per la raccolta dei dati, procedendo all'analisi con la Grounded Theory Methodology. Per il secondo studio sono state utilizzate interviste semi-strutturate, analizzate attraverso L'Analisi Tematica. I risultati hanno evidenziato una forte frammentazione nel mondo simbolico-emotivo del sistema dei servizi, così disgregati, ma così univoci nella loro richiesta di poter contare su una rete più solida, efficace e sostenibile. Viene auspicato un lavoro integrato a livello organizzativo, avendo cura di chi cura e soprattutto dei vissuti, e un processo di "disclosure" e di attivazione di consapevolezza, alla luce del forte diniego spesso agito dagli autori di violenza, ma anche dagli stessi addetti ai lavori che prendono in carica le persone coinvolte

The Crystal Fortress: the world of children witnessing domestic violence in the words of health and welfare professionals

Witnessing Domestic Violence (WDV) is defined by The Child Welfare Information Gateway as a psychological violence that has dramatic consequences on the psychophysical health of children. In order to contribute to the taking charge of Domestic Violence (DV) and according to researchers who show the role of fatherhood in ending the phenomenon, ViDaCS project puts fathers in their children's shoes by making them witness a scene of strong family conflict through the virtual reality. In order to structure the scene of DV, 16 Neapolitan health professionals dealing with children WDV were selected through a theoretical intentional sampling and interviewed. Narrative focused interviews were carried out, transcribed verbatim and analyzed through the Grounded Theory Methodology, using the ATLAS.ti 8 software. 319 codes were assigned to the texts, then grouped in 10 categories and 4 macro-categories. The “Cristal Fortress” emerged as the core category, summarizing the world of the children WDV in the voice of Neapolitan professionals; a world where family that would protect like a fortress, is made fragile by the “inexplicable and senseless violence”. The analysis also allowed to investigate the experiences and suggestions of the participants with respect to the network of services. In fact, the core category also reflected a network that should protect like a fortress, but which is made fragile by the difficulty of communication among the services. It revealed the importance of offering children a solid space in which to be protected, and it helped to think about useful guidelines for services dealing with WDV

Targeting interleukin-1β protects from aortic aneurysms induced by disrupted transforming growth factor β signaling

Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor β (TGF-β) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) in SMCs. This danger signal later recruited innate immunity in the adventitia through chemokine (C-C motif) ligand 2 (CCL2) and modified the mechanical properties of the aortic wall, thus favoring vessel dilation. SMC-specific Smad4 deletion in Il1r1- or Ccr2-null mice resulted in milder aortic pathology. A chronic treatment with anti-IL-1β antibody effectively hampered aneurysm development. These findings identify a mechanistic target for controlling the progression of aneurysms with compromised TGF-β signaling, such as those driven by SMAD4 mutations

Drawingvoice 2.0: classroom joint designing and Facebook interactions to develop reflexivity and awareness

Drawingvoice 2.0 is an instructional method of collaborative pencil and paper drawing to use in the school classroom, followed by Facebook interaction on the drawing produced in class. It is based on a participatory and meta reflective approach, explicitly aimed at deconstructing, negotiating, and reconstructing the meaning that students attribute to themselves regarding their professional expectations and educational pathways. In particular, the collaborative pencil and paper drawing allows for the student’s emotional symbolisation processes underlying their educational pathway. Drawingvoice 2.0 induces a multidimensional cognitive and meta-cognitive process further supported by the following interaction on Facebook. Therefore, the World Wide Web is the added resource for sharing and deepening the classmates’ discussion. Finally, Drawingvoice 2.0 supported structural group interaction and was an important supportive and instructional method to bring about transformational and developmental training practices. As the main result, in our experience, psychology students increased their reflectivity about their strengths and threats in being psychologists within their cultural contexts and potential positive resources underlying their choice. Drawingvoice 2.0 thus enhanced their self-awareness about the lights and shadows of their training and future professional career.info:eu-repo/semantics/publishedVersio

Ending Intimate Partner Violence (IPV) and Locating Men at Stake: An Ecological Approach

Interventions for ending intimate partner violence (IPV) have not usually provided integrated approaches. Legal and social policies have the duty to protect, assist and empower women and to bring offenders to justice. Men have mainly been considered in their role as perpetrators to be subjected to judicial measures, while child witnesses of violence have not been viewed as a direct target for services. Currently, there is a need for an integrated and holistic theoretical and operational model to understand IPV as gender-based violence and to intervene with the goal of ending the fragmentation of existing measures. The EU project ViDaCS—Violent Dads in Child Shoes—which worked towards the deconstruction and reconstruction of violence’s effects on child witnesses, has given us the opportunity to collect the opinions of social workers and child witnesses regarding violence. Therefore, the article describes measures to deal with IPV, proposing functional connections among different services and specific preventative initiatives. Subsequently, this study will examine intimate partner violence and provide special consideration to interventions at the individual, relational, organizational and community levels. The final goal will be to present a short set of guidelines that take into account the four levels considered by operationalizing the aforementioned ecological principles

Lack of kinase-independent activity of PI3Kγ in locus coeruleus induces ADHD symptoms through increased CREB signaling.

Although PI3Kγ has been extensively investigated in inflammatory and cardiovascular diseases, the exploration of its functions in the brain is just at dawning. It is known that PI3Kγ is present in neurons and that the lack of PI3Kγ in mice leads to impaired synaptic plasticity, suggestive of a role in behavioral flexibility. Several neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), involve an impairment of behavioral flexibility. Here, we found a previously unreported expression of PI3Kγ throughout the noradrenergic neurons of the locus coeruleus (LC) in the brainstem, serving as a mechanism that regulates its activity of control on attention, locomotion and sociality. In particular, we show an unprecedented phenotype of PI3Kγ KO mice resembling ADHD symptoms. PI3Kγ KO mice exhibit deficits in the attentive and mnemonic domains, typical hyperactivity, as well as social dysfunctions. Moreover, we demonstrate that the ADHD phenotype depends on a dysregulation of CREB signaling exerted by a kinase-independent PI3Kγ-PDE4D interaction in the noradrenergic neurons of the locus coeruleus, thus uncovering new tools for mechanistic and therapeutic research in ADHD

Poorly differentiated clusters (PDC) in colorectal cancer: Does their localization in tumor matter?

Poorly differentiated clusters (PDC) are aggregates of at least five neoplastic cells lacking evidence of glandular differentiation. By definition, they can be present at the invasive front (peripheral PDC or pPDC) and within the tumor stroma (central PDC or cPDC). In colorectal cancer (CRC), PDC are considered adverse prognosticators and seem to reflect epithelial mesenchymal transition (EMT). In this study, we have investigated the immuno-expression of two EMT-related proteins, E-cadherin and \u3b2-catenin, in PDC of primary CRCs and matched liver metastases. pPDC always showed nuclear \u3b2-catenin staining and diffusely reduced/absence of E-cadherin expression as opposed cPDC which showed nuclear \u3b2-catenin immunoreactivity and E-cadherin expression in about 50% of cases. In addition, the pattern of \u3b2-catenin and E-cadherin expression differed between PDC and the main tumor, and between primary CRC and liver metastasis (LM), in a percentage of cases. A discordant pattern of \u3b2-catenin and E-cadherin expression between pPDC and cPDC, between main tumor and cPDC, and between primary CRC and LM, confirms that EMT is a dynamic and reversible process in CRC. On the overall, this suggests that pPDC and cPDC are biologically different. We may advocate that PDC develop at the tumor center (cPDC) and then some of them migrate towards the tumor periphery while progressively completing EMT process (pPDC). Based on these results, PDC presence and counting may have different prognostic relevance if the assessment is done at the invasive front of the tumor or in the intratumor stroma

“Just before”. Intimate partner violence: Virtual reality and a new focus for perpetrators’ motivation for treatment

The Istanbul Convention (art. 16) regulates interventions to prevent and combat male violence against women, stressing the need for intervention to reduce perpetrators’ recidivism. In this research the paternal function is a motivating factor for treatment that facilitates men's access to the awareness of their violence on children, especially when they are put into their shoes. In this case virtual immersive reality becomes an efficient tool as it can transfer the user and his emotionality into the world of the victims. To explore the impact on the recognition of responsibility for one's own violent actions on the other and on the motivation for treatment, forty-six men participated in ViDaCS serious game, involving a virtual scene of a couple a moment before the outburst of negative emotions takes over, first in the role of a man, then in that of a child who witnesses the scene. Quanti-qualitative questionnaires and focused interviews were administered to participants. Data were respectively analysed with frequency analysis and thematic analysis. Results allowed the men who have lived the scene to access emotional contents and experiences, demonstrating the effectiveness of VR (Virtual Reality) in creating a trigger in the man's awareness and his internal motivation to change.