Psicoanalisi in forma e azione Di Donato, Veronica; Di Nunzio, Chiara; Dionisi, Beatrice ...
Ricerca psicoanalitica,
04/2021, Letnik:
32, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Il lavoro presenta una riflessione a partire dall’esperienza delle autrici sulla formazione in psicoanalisi. Negli ultimi anni, il percorso formativo si è sempre più complessificato prevedendo un ...iter articolato in quattro pilastri formativi: seminari teorici, supervisione, analisi personale e tirocinio. Nello specifico, le autrici approfondiscono l’esperienza del tirocinio e quella della supervisione, nel tentativo di narrare lo snodarsi del processo formativo tra criticità e trasformazione. La parte dedicata al tirocinio esplora il faticoso transito da una psicoanalisi ‘privata’ ad una ‘pubblica’ ponendo l’accento sui vissuti e gli interrogativi del tirocinante stesso. La supervisione viene trattata come spazio di apprendimento e di rielaborazione delle prime esperienze analitiche dell’allievo che avvengono durante il tirocinio. La natura contestuale di tali esperienze rende la supervisione un processo ancora più complesso in cui è necessario coniugare la logica interna dell’apprendimento formativo con la sua applicabilità nei contesti.
Transient receptor potential melastatin-8 (TRPM8) represents an emerging target in prostate cancer, although its mechanism of action remains unclear. Here, we have characterized and investigated the ...effects of TRPM8 modulators in prostate cancer aggressiveness disclosing the molecular mechanism underlying their biological activity. Patch-clamp and calcium fluorometric assays were used to characterize the synthesized compounds. Androgen-stimulated prostate cancer-derived cells were challenged with the compounds and the DNA synthesis was investigated in a preliminary screening. The most effective compounds were then employed to inhibit the pro-metastatic behavior of in various PC-derived cells, at different degree of malignancy. The effect of the compounds was then assayed in prostate cancer cell-derived 3D model and the molecular targets of selected compounds were lastly identified using transcriptional and non-transcriptional reporter assays. TRPM8 antagonists inhibit the androgen-dependent prostate cancer cell proliferation, migration and invasiveness. They are highly effective in reverting the androgen-induced increase in prostate cancer cell spheroid size. The compounds also revert the proliferation of castrate-resistant prostate cancer cells, provided they express the androgen receptor. In contrast, no effects were recorded in prostate cancer cells devoid of the receptor. Selected antagonists interfere in non-genomic androgen action and abolish the androgen-induced androgen receptor/TRPM8 complex assembly as well as the increase in intracellular calcium levels in prostate cancer cells. Our results shed light in the processes controlling prostate cancer progression and make the transient receptor potential melastatin-8 as a 'druggable' target in the androgen receptor-expressing prostate cancers.
Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing ...severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells.
The thymus plays a fundamental role in establishing and maintaining central and peripheral tolerance and defects in thymic architecture or AIRE expression result in the development of autoreactive ...lymphocytes. Patients with partial DiGeorge Syndrome (pDGS) and Down Syndrome (DS) present alterations in size and architecture of the thymus and higher risk to develop autoimmunity. We sought to evaluate thymic architecture and thymocyte development in DGS and DS patients and to determine the extent to which thymic defects result in immune dysregulation and T cell homeostasis perturbation in these patients. Thymi from pediatric patients and age-matched controls were obtained to evaluate cortex and medullary compartments, AIRE expression and thymocyte development. In the same patients we also characterized immunophenotype of peripheral T cells. Phenotypic and functional characterization of thymic and peripheral regulatory T (Treg) cells was finally assessed. Histologic analysis revealed peculiar alterations in thymic medulla size and maturation in DGS and DS patients. Perturbed distribution of thymocytes and altered thymic output was also observed. DGS patients showed lower mature CD4
and CD8
T cell frequency, associated with reduced proportion and function of Tregs both in thymus and peripheral blood. DS patients showed increased frequency of single positive (SP) thymocytes and thymic Treg cells. However, Tregs isolated both from thymus and peripheral blood of DS patients showed reduced suppressive ability. Our results provide novel insights on thymic defects associated with DGS and DS and their impact on peripheral immune dysregulation. Indeed, thymic abnormalities and defect in thymocyte development, in particular in Treg cell number and function could contribute in the pathogenesis of the immunodysregulation present in pDGS and in DS patients.
Objectives
We sought to evaluate the effectiveness of post-mortem cardiac magnetic resonance (PM-CMR) for the identification of myocardial ischemia as cause of sudden cardiac death (SCD) when the ...time interval between the onset of ischemia and SCD is ≤ 90 min.
Methods
PM-CMR was performed in 8 hearts explanted from pigs with spontaneous death caused by occlusion of the left anterior descending coronary artery: 4 with SCD after ≤ 40 min of coronary occlusion and 4 between 40 and 90 min. PM-CMR included conventional T1 and T2-weighted image and T1, T2, and T2* mapping techniques. Imaging data were compared and validated with immunohistochemical evaluation of the altered proportion and redistribution of phosphorylated versus non-phosphorylated connexin 43 (CX43 and npCX43, respectively), an established molecular marker of myocardial ischemia.
Results
At T2-weighted images, the ischemic core was hypointense (core/remote ratio 0.67 ± 0.11) and surrounded by and hyperintense border zone. Compared to remote myocardium, the ischemic core had higher T1 (
p
= 0.0008), and lower T2 (
p
= 0.007) and T2* (
p
= 0.002). Cytoplasmatic npX43 and the npCX43/CX43 ratio were significantly higher in animals deceased > 40 min than in others.
Conclusion
PM-CMR can reliably detect early signs of myocardial damage induced by ischemia, based on conventional pulse sequences complemented by a novel ad hoc application of quantitative mapping techniques.
Key Points
• Post-mortem MRI may help to understand cause of sudden cardiac death.
• Post-mortem MRI allows detection of signs of myocardial ischemia as cause of sudden cardiac death within 90 and 40 min following coronary occlusion as demonstrated in a pig model of myocardial ischemia.
• Signs of myocardial ischemia using conventional and mapping MRI technique are associated with the immunohistochemical changes of phosphorylated and dephosphorylated connexin-43 which is an established molecular marker of myocardial ischemia.
21q22.2–3 deletion is the most common copy number alteration in prostate cancer (PCa). The genomic rearrangement results in the androgen-dependent de novo expression of ETS-related gene (ERG) in ...prostate cancer cells, a condition promoting tumor progression to advanced stages of the disease.
Interestingly, ERG expression characterizes 5–30% of tumor precursor lesions – High Grade Prostatic Intraepithelial Neoplasia (HGPIN) - where its role remains unclear.
Here, by combining organoids technology with Click-chemistry coupled Mass Spectrometry, we demonstrate a prominent role of ERG in remodeling the protein secretome of prostate progenitors. Functionally, by lowering autocrine Wnt-4 signaling, ERG represses canonical Wnt pathway in prostate progenitors, and, in turn, promotes the accumulation of DNA double strand breaks via Gsk3β-dependent degradation of the tumor suppressor Nkx3.1. On the other hand, by shaping extracellular paracrine signals, ERG strengthens the pro-oxidative transcriptional signature of inflammatory macrophages, which we demonstrate to infiltrate pre-malignant ERG positive prostate lesions.
These findings highlight previously unrecognized functions of ERG in undermining adult prostate progenitor niche through cell autonomous and non-autonomous mechanisms. Overall, by supporting the survival and proliferation of prostate progenitors in the absence of growth stimuli and promoting the accumulation of DNA damage through destabilization of Nkx3.1, ERG could orchestrate the prelude to neoplastic transformation.
•Expression of ERGM40 in mouse prostate organoids promotes their survival and growth in the absence of Egf.•ERGM40 alters the extracellular signaling network of mouse prostate organoids.•Canonical Wnt pathway is substantially reduced in ERG + prostate organoids due to decreased autocrine signaling of Wnt4.•Gsk3b promotes Nkx3.1 proteolysis and, in turn, accumulation of double strand breaks in ERG + prostate organoids.•Paracrine signaling of ERG + prostate organoids modulates Arginase 1 expression in M1-polarized macrophages.
Down syndrome (DS) patients prematurely show clinical manifestations usually associated with aging. Their immune system declines earlier than healthy individuals, leading to increased susceptibility ...to infections and higher incidence of autoimmune phenomena. Clinical features of accelerated aging indicate that trisomy 21 increases the biological age of tissues. Based on previous studies suggesting immune senescence in DS, we hypothesized that induction of cellular senescence may contribute to early thymic involution and immune dysregulation. Immunohistochemical analysis of thymic tissue showed signs of accelerated thymic aging in DS patients, normally seen in older healthy subjects. Moreover, our whole transcriptomic analysis on human Epcam-enriched thymic epithelial cells (hTEC), isolated from three DS children, which revealed disease-specific transcriptomic alterations. Gene set enrichment analysis (GSEA) of DS TEC revealed an enrichment in genes involved in cellular response to stress, epigenetic histone DNA modifications and senescence. Analysis of senescent markers and oxidative stress in hTEC and thymocytes confirmed these findings. We detected senescence features in DS TEC, thymocytes and peripheral T cells, such as increased β-galactosidase activity, increased levels of the cell cycle inhibitor p16, telomere length and integrity markers and increased levels of reactive oxygen species (ROS), all factors contributing to cellular damage. In conclusion, our findings support the key role of cellular senescence in the pathogenesis of immune defect in DS while adding new players, such as epigenetic regulation and increased oxidative stress, to the pathogenesis of immune dysregulation.
High- and low-risk endometrial carcinoma (EC) differ in whether or not a lymphadenectomy is performed. We aimed to develop MRI-based radio-genomic models able to preoperatively assess lymph-vascular ...space invasion (LVSI) and discriminate between low- and high-risk EC according to the ESMO-ESGO-ESTRO 2020 guidelines, which include molecular risk classification proposed by "ProMisE". This is a retrospective, multicentric study that included 64 women with EC who underwent 3T-MRI before a hysterectomy. Radiomics features were extracted from T2WI images and apparent diffusion coefficient maps (ADC) after manual segmentation of the gross tumor volume. We constructed a multiple logistic regression approach from the most relevant radiomic features to distinguish between low- and high-risk classes under the ESMO-ESGO-ESTRO 2020 guidelines. A similar approach was taken to assess LVSI. Model diagnostic performance was assessed via ROC curves, accuracy, sensitivity and specificity on training and test sets. The LVSI predictive model used a single feature from ADC as a predictor; the risk class model used two features as predictors from both ADC and T2WI. The low-risk predictive model showed an AUC of 0.74 with an accuracy, sensitivity, and specificity of 0.74, 0.76, 0.94; the LVSI model showed an AUC of 0.59 with an accuracy, sensitivity, and specificity of 0.60, 0.50, 0.61. MRI-based radio-genomic models are useful for preoperative EC risk stratification and may facilitate therapeutic management.
The ongoing revolution in the plastic sector is the use of renewable and compostable materials obtained from biomass. However, their mechanical strength and thermal stability are generally not ...sufficient for practical applications. This study investigates the influence of natural additives on the physical-mechanical properties of a new biobased compostable bioplastic, SP-Milk®, produced from milk scraps. To provide this matrix the appropriate mechanical and thermal properties for daily use while leaving its compostability unchanged, the effect of incorporating vegetal fibres and organic particulates into the bulk bioplastic was investigated. Mechanical tests showed that fibres with a length of 2 mm are capable of increasing ductility by up to 97% compared with the original matrix, whereas fibres with a length of 10 mm led to a more effective reinforcement due to the residual resistance effect, increasing the final compressive strain from 20% (original matrix) to 70.9%. The addition of particulate yielded a harder and more resistant material, and the elastic modulus increased by 21%, although with loss of ductility, compared to SP-Milk® alone. The combination of fibres and particles resulted in the preservation of the positive effects of both components, showing a higher elastic modulus (240 ± 20 MPa, compared to 199 ± 12 MPa for the matrix), higher ductility (+50%) and higher strain at failure (+30%), compared with the matrix. Excellent compatibility between the polymeric matrix and both the fibres and the granules was confirmed using scanning electron microscopy. The thermal analysis demonstrated improved thermal stability particularly because of the effect of the combination of granules and fibres. The results validate that natural reinforcement agents are effective and ecologically advantageous.
The ongoing revolution in the plastic sector is the use of renewable and compostable materials obtained from biomass. In this paper the influence of natural reinforcing agents on the properties of a milk-based compostable bioplastic is investigated.
Edible insects have been recognized as a more sustainable source of nutrients and bio-active compounds than animal-based products, in line with classical vegetable sources such as legumes. In this ...study, we assessed the antioxidant properties of four edible insects (silkworms, grasshoppers, mealworms and giant worms) and four legume seeds (lentils, chickpeas,
peas and grass peas).
After the aqueous extraction or
simulated digestion process, selected products were assessed for: (i)
antioxidant capacity through Ferric Reducing Antioxidant Power (FRAP) assay; (ii) the ability to reduce free radicals production induced by a pro-oxidant agent in cells of human colonic mucosa.
All the aqueous extracts and digesta of edible insects displayed significantly higher
antioxidant activity than legumes. Moreover, edible insects at all tested concentrations were able to exert an antioxidant effect in the cellular model, while legumes were effective mainly at high concentrations.
Despite human trials are need to confirm and define these results in a physiological situation, here we suggest a role for edible insects in oxidative stress prevention. Since oxidative stress is strongly correlated with several intestinal pathologies, the results obtained could be interesting for the prevention and relief of the negative symptoms, offering new advantages to their already known ecological and nutritional properties.
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