La relazione che organizza il contesto sanitario: domanda dell’utenza e risposta dei servizi sanitari, nel territorio e nell’ospedale - The relationship which organizes the healthcare context: users’ demand and response of healthcare services, in the territory and the hospital

Our intent is to present citizens’ demand of health care services in Italy through a research structured in three studies. We used the Emotional Text Analysis (ETA) to lead the three s tudies: the first study regarded the citizens’expectations of the healthcare services, the second study regarded the point of view of the hospital personnel (medical doctors and nurses), the third regarded the point of view of the General Practitioners onthe health care services. These three studies are briefly presented. Data and outcome of an Assumed Similarity Test applied to all experimental subjects of the three studies in order to make a comparison among them, are also presented. The findings of the Emotional Text Analysis show that citizens, potential users of health services, center their requests on their individual subjectivity, and seek answers both to their suffering and to the feeling of alienation that characterizes the being sick feeling that makes them go to a medical doctor. For their part, general practitioners and hospital doctors immediately transform this subjective feeling in an objective medical diagnosis. Here a first gap emerges between patient’s demand and medical response, leavingthe possibility of an alliance on the diagnosis in order to jointly fight the disease. It has long been in place though a change that has expelled the patient also from sharing the diagnostic process, increasingly taken from self-centered dynamics within the healthcare system. This widens the gap between the request of the citizens and the response of the health services, that contributes to that conflictual growth to which defensive medicine gives a dysfunctional answer. The Assumed Similarity Test contributes to the interpretation of the health care dynamic identified in the Emotional Text Analysis; particularly in regard to the unfolding conflict, given by the hypothesis emerging from the data analysis, that a feeling of closeness for the hospital personnel goes along with an emotional stance of overpowering the othe

La cultura locale di Roma e delle sue periferie urbane nella rappresentazione dei resti archeologici - The local culture of Rome and its urban suburbs in the representation of the archaeological remains

Nel presente lavoro viene proposta l’analisi della relazione come luogo del problema che caratterizza l’intervento psicologico clinico quale alternativa alla diagnosi. Tre esempi clinici aiutano a cogliere come la relazione sia il luogo del problema che s’intende affrontare; sia con il lavoro d’assistenza in ambito familiare, che scolastico o sociale. La funzione psicologica può cambiare radicalmente il lavoro assistenziale, mutando obiettivi inutili e obsoleti in interventi efficaci. Ciò è possibile se l’intervento cambia il proprio obiettivo, spostandolo dalla singola persona disabile o problematica, alla relazione entro la quale l’intervento si contestualizza.The research, carried out within a project research of national interest (PRIN) directed by archaeologist Professor Clementina Panella, has the purpose to detect the local culture of inhabitants of the center and the outskirts of Rome, paying attention to the archaeological remains and their cultural contribution. Three components of local culture emerged in this research; all of them are reported to a cultural context that people feel as organized by the pursuit of power and the enhancement of the mass media as factors that give notoriety and popularity then power. One of the three cultural repertoires, characterized by young participants and residents in the outskirts of Rome, enhances the archaeological remains as components of a fun culture. The fun, in combination with culture, is experienced as an effective alternative to the power and the pursuit of powe

Reprogramming the anti-tumor immune response via CRISPR genetic and epigenetic editing

Precise clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genetic and epigenetic manipulation of the immune response has become a promising immunotherapeutic approach towards combating tumorigenesis and tumor progression. CRISPR-based immunologic reprograming in cancer therapy comprises the locus-specific enhancement of host immunity, the improvement of tumor immunogenicity and the suppression of tumor immunoevasion. To date, the ex vivo re-engineering of immune cells directed to inhibit the expression of immune checkpoints or to express synthetic immune receptors (chimeric antigen receptor therapy) has shown success in some settings, such as in the treatment of melanoma, lymphoma, liver and lung cancer. However, advancements in nuclease-deactivated CRISPR-associated nuclease-9 (dCas9)-mediated transcriptional activation or repression and Cas13-directed gene suppression presents novel avenues for the development of tumor immunotherapies. In this review, the basis for development, mechanism of action and outcomes from recently published Cas9-based clinical trial (genetic editing) and dCas9/Cas13-based pre-clinical (epigenetic editing) data are discussed. Lastly, we review cancer immunotherapy-specific considerations and barriers surrounding use of these approaches in the clinic

A BARF1-specific mAb as a new immunotherapeutic tool for the management of EBV-related tumors.

The use of monoclonal antibodies (mAb) for the diagnosis and treatment of malignancies is acquiring an increasing clinical importance, thanks to their specificity, efficacy and relative easiness of use. However, in the context of Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can benefit from therapeutic mAb targeting specific B-cell lineage antigens. To overcome this limitation, we generated a new mAb specific for BARF1, an EBV-encoded protein with transforming and immune-modulating properties. BARF1 is expressed as a latent protein in nasopharyngeal (NPC) and gastric carcinoma (GC), and also in neoplastic B cells mainly upon lytic cycle induction, thus representing a potential target for all EBV-related malignancies. Considering that BARF1 is largely but not exclusively secreted, the BARF1 mAb was selected on the basis of its ability to bind a domain of the protein retained at the cell surface of tumor cells. In vitro, the newly generated mAb recognized the target molecule in its native conformation, and was highly effective in mediating both ADCC and CDC against BARF1-positive tumor cells. In vivo, biodistribution analysis in mice engrafted with BARF1-positive and -negative tumor cells confirmed its high specificity for the target. More importantly, the mAb disclosed a relevant antitumor potential in preclinical models of NPC and lymphoma, as evaluated in terms of both reduction of tumor masses and long-term survival. Taken together, these data not only confirm BARF1 as a promising target for immunotherapeutic interventions, but also pave the way for a successful translation of this new mAb to the clinical use

Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells.

The effects of dexamethasone, a synthetic glucocorticoid, and of N,N-dimethylformamide on in vitro growth and differentiation and on proto-oncogene expression of human rhabdomyosarcoma cells were studied. RD/18 clone cells (derived from the embryonal rhabdomyosarcoma cell line RD) treated with 100 nM dexamethasone showed an almost complete block of differentiation: about 5% myosin-positive cells were observed after 2 weeks of culture in dexamethasone-supplemented differentiation medium, compared to 20% of untreated cultures. Dexamethasone also induced a 20-30% growth inhibition and a more flattened morphology. The treatment with N,N-dimethylformamide induced a significantly increased proportion of myosin-positive cells (reaching about 30%) and a 40% growth inhibition. Induction of differentiation inversely correlated with the levels of c-myc proto-oncogene expression: after a 2 week culture dexamethasone-treated cells showed the highest c-myc expression and N,N-dimethylformamide-treated cells the lowest. Culture conditions per se down-modulated c-erbB1 and up-regulated c-jun expression, with no relationship to the differentiation pattern. Other proto-oncogenes were not expressed (c-sis, N-myc, c-mos, c-myb) or were not modulated (c-fos, c-raf). Therefore dexamethasone and N,N-dimethylformamide, both causing a decreased growth rate, showed opposing actions on myogenic differentiation and on c-myc proto-oncogene expression of human rhabdomyosarcoma cells

Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients

Background: Metastatic breast cancer (mBC) is a heterogeneous disease with varying responses to treatments and clinical outcomes, still requiring the identification of reliable predictive biomarkers. In this context, liquid biopsy has emerged as a powerful tool to assess in real-time the evolving landscape of cancer, which is both orchestrated by the metastatic process and immune-surveillance mechanisms. Thus, we investigated circulating tumor cells (CTCs) coupled with peripheral T-cell immunity to uncover their potential clinical relevance in mBC. Methods: A cohort of 20 mBC patients was evaluated, before and one month after starting therapy, through the following liquid biopsy approaches: CTCs enumerated by a metabolism-based assay, T-cell responses against tumor-associated antigens (TAA) characterized by interferon-γ enzyme-linked immunosorbent spot (ELISpot), and the T-cell receptor (TCR) repertoire investigated by a targeted next-generation sequencing technique. TCR repertoire features were characterized by the Morisita’s overlap and the Productive Simpson Clonality indexes, and the TCR richness. Differences between groups were calculated by Fisher’s, Mann-Whitney or Kruskal-Wallis test, as appropriate. Prognostic data analysis was estimated by Kaplan-Meier method. Results: Stratifying patients for their prognostic level of 6 CTCs before therapy, TAA specific T-cell responses were detected only in patients with a low CTC level. By analyzing the TCR repertoire, the highest TCR clonality was observed in the case of CTCs under the cut-off and a positive ELISpot response (p=0.03). Whereas, at follow-up, patients showing a good clinical response coupled with a low number of CTCs were characterized by the most elevated TCR clonality (p<0.05). The detection of CTCs≥6 in at least one time-point was associated with a lower TCR clonality (p=0.02). Intriguingly, by combining overall survival analysis with TCR repertoire, we highlighted a potential prognostic role of the TCR clonality measured at follow-up (p=0.03). Conclusion: These data, whether validated in a larger cohort of patients, suggest that the combined analysis of CTCs and circulating anti-tumor T-cell immunity could represent a valuable immune-oncological biomarker for the liquid biopsy field. The clinical application of this promising tool could improve the management of mBC patients, especially in the setting of immunotherapy, a rising approach for BC treatment requiring reliable predictive biomarkers

Towards Critical Occidentalism Studies: Re-inventing the 'West' and 'Japan' in Mangaesque Popular Cultures

This paper investigates the reproduction of the imagined geography of the ‘West’ in contemporary Japan by employing a relational, intersectional and positional approach in order to examine Occidentalism and its hegemonic identification and othering process. Particular attention will be paid to emerging Japanese subcultures enacting a parodic and sexualised re-invention of Westernness and Japaneseness within a globalising mangaesque media mix

Treatment plan comparison in acute and chronic respiratory tract diseases : an observational study of doxophylline vs. theophylline

BACKGROUND: The main objective of this article is to estimate the global cost related to the use of the two drugs (associated drugs, specialist visits, hospital admissions, plasma drug monitoring). METHODS: The drug prescriptions were extracted from the Information System of the Pharmaceutical Prescriptions of the Marche Region for each ATC code in the years 2008-2012 and the number of patients per year and other outcomes measure were obtained. RESULTS: 13,574 patients were treated with theophylline and 19,426 patients with doxophylline. The number of patients treated was approximately 5,000 per year. Co-prescription with other drugs, use of corticosteroids, mean number of visits and hospital admissions (per 100 patients) were lower for doxophylline vs theophylline (1.55vs5.50, 0.3vs0.7, 2.05vs3.73 and 1.57vs3.3 respectively). The annual mean cost per patient was €187.4 for those treated with doxophylline and €513.5 for theophylline. CONCLUSIONS: In our study, doxophylline resulted to be associated with a reduction of the overall cost