La corazza protettiva della dignità

Prezzo o dignità? Analizzando il ruolo che il concetto di dignità ha via acquisito, soprattutto dopo la fine della seconda guerra mondiale, Remo Bodei, nel capitolo VII di Dominio e sottomissione, intitolato «Le vicissitudini della dignità», parte dalla celebre contrapposizione tra il pensiero di Hobbes e il pensiero di Kant a proposito del valore dell’essere umano. Mentre per Hobbes, il valore dell’uomo consiste nel suo prezzo —«Il valore o il pregio di un uomo consiste, come di tutte le alt..

RelA/NF-kappaB recruitment on the bax gene promoter antagonizes p73-dependent apoptosis in costimulated T cells

The balance between antiapoptotic and proapoptotic proteins of the Bcl-2 family is critical in determining the fate of T cells in response to death stimuli. Proapoptotic genes, such as bax, are generally regulated by the p53 family of transcription factors, whereas NF-kappaB subunits can activate the transcription of antiapoptotic Bcl-2 members. Here, we show that CD28 activation protects memory T cells from irradiation-induced apoptosis by both upregulating bcl-xL and inhibiting bax gene expression. We found that p73, but not p53, binds to and trans-activates the bax gene promoter in irradiated T cells. The activation of RelA/NF-kappaB subunit in CD28 costimulated T cells and its binding onto the bax gene promoter results in suppression of bax transcription and decrease in both p73 and RNA polymerase II recruitment in vivo. RelA recruitment on the bax gene promoter is also accompanied by the lost of p300 binding and the parallel appearance of histone deacetylase-1-containing complexes. These findings identify RelA/NF-kappaB as a critical regulator of T-cell survival by affecting the balance of Bcl-2 family members

La structure de la révolution numérique (philosophie de la technologie)

De quoi la révolution numérique est-elle la révolution ? Le premier niveau d analyse s inscrit sur le plan de l histoire. Il vise à dégager la structure historique de la révolution numérique, en délimitant d abord son périmètre diachronique et en dégageant sa place particulière au sein de l histoire générale des techniques. L hypothèse, c est que la révolution numérique n est pas un changement d outillage mais un événement d histoire, qui s inscrit dans le long processus de la machinisation de l Occident et de la succession des systèmes techniques pour aboutir à l émergence d un nouveau système technique : la révolution numérique, c est la révolution de notre infrastructure technique systémique, c est-à-dire l avènement du système technique numérique . Dans cette partie, nous privilégions le terrain historique et les données empiriques qu il fournit, au nom d une philosophie de la technologie fermement opposée à toute métaphysique misotechnique. Le second niveau d analyse s inscrit sur le plan de la perception. Au-delà de la seule révolution numérique, il vise à dégager la structure phénoménologique de toute révolution technique, en remontant aux conditions techniques de toute perception en général. L hypothèse, c est qu une révolution technique est toujours une révolution ontophanique, c est-à-dire un ébranlement du processus par lequel l être (ontos) nous apparaît (phaïnô) et, par suite, un bouleversement de l idée même que nous nous faisons de la réalité. Nous nous appuyons ici sur la notion de phénoménotechnique empruntée à Gaston Bachelard, qui nous conduit à défendre un constructivisme phénoménologique selon lequel toute technique est une matrice ontophanique, dans laquelle se coule notre expérience-du-monde possible. Comme les précédentes, la révolution numérique apparaît alors comme une révolution de nos structures perceptives, dont la violence phénoménologique permet au passage d expliquer le succès et le déclin de la notion de virtuel. De cette dernière, nous proposons une généalogie critique et nous montrons qu elle n a été jusqu ici qu une tentative ratée d élucider la phénoménalité numérique, en raison de la rêverie de l irréel qu elle induit. Le troisième niveau d analyse s inscrit sur le plan de la phénoménalité numérique enfin abordée dans sa positivité. Il vise à saisir la structure ontophanique de la révolution numérique, c est-à-dire la nature de l être des êtres numériques. L hypothèse, c est que l ontophanie numérique résulte de onze caractéristiques phénoménologiques propres à la matière calculée, qui sont présentées dans un ordre didactique favorisant la compréhension globale du phénomène numérique. Il s agit de la nouménalité, l idéalité, l interactivité, la virtualité, la versatilité, la réticularité, la reproductibilité instantanée, la réversibilité, la destructibilité, la fluidité et la ludogénéité. Nous terminons alors en analysant la responsabilité des activités de conception-création dans la genèse phénoménotechnique du réel et en particulier le rôle du design dans la constitution créative de l ontophanie numérique. En tant qu activité phénoménotechnique, le design est non seulement une activité créatrice d ontophanie, mais encore une activité intentionnellement factitive, c est-à-dire qui vise à faire-être autant qu à faire-faire, en vue de projeter l enchantement du monde. C est pourquoi le design numérique, parce qu il a la capacité d engendrer de nouveaux régimes d expériences interactives, joue un rôle essentiel dans le modelage de la révolution numérique. La révolution numérique, c est aussi quelque chose qui se sculpte et se façonne, se coule et se moule dans les projets des designers. C est une révolution de notre capacité à faire le monde, c est-à-dire à créer de l être.What is the digital revolution the revolution of ? What is turned upside down and disturbed, reformed and transformed, in the so-called digital revolution ? To answer this, digital revolution is approached here from the point of view of a philosophy of technology which assumes that our being-in-the-world is fundamentally conditioned by technique and always has been. The first level of this approach focuses on the historical structure of the digital revolution. The hypothesis is that the digital revolution is an event in history that is part of the long process of mechanization in the West and consists in the advent of a digital technical system . The second level concerns the phenomenological structure of the digital revolution. The hypothesis is that a technical revolution is always ontophanic, that is to say a shaking of the structures of perception and of the process through which the being appears to us. This results in phenomenological constructivism, based on the notion of phenomenotechnique, which ultimately condemns the notion of virtual . The third and final level of analysis focuses on the ontophanic structure of the digital revolution. The hypothesis is that digital ontophany consists of eleven fundamental characteristics : noumenality, ideality, interactivity, virtuality, versatility, reticularity, instant reproducibility, reversibility, destructibility, fluidity and ludogeneity. The role of design as a phenomenotechnical activity that shapes the world is therefore essential in the creative development of the digital ontophany.PARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF

Glucocorticoids and Antivirals for HBV Reactivation in Onco-Hematologic Patients.

Patients with inactive or occult hepatitis B virus infection and onco-hematological malignancies are at risk of hepatitis flare, hepatic failure and death due to chemotherapy-mediated reactivation. Nucleot(s)ide analogues can reduce reactivation risks and/or hepatitis. However, immuno-mediated phenomena combine to determine liver damage and clinical outcome. We describe in this report two patients with onco-hematological malignancies and hepatitis B reactivation after chemotherapy in whom glucocorticoids were added to nucleot(s)ide. Antiviral therapy was effective on replication, while glucocorticoids managed hyperergic response. One patient without underlying liver disease survived, while the second died and the autopsy demonstrated cirrhosis undetected before death. This clinical trial suggests that in patients with onco-hematological malignancies and altered liver function tests in spite of effective antiviral response, glucocorticoids could control the effects of immune response. However prognosis and survival are related to the underlying liver status

Preoperative Predictive Factors of Successful Weight Loss and Glycaemic Control 1 Year After Gastric Bypass for Morbid Obesity

BACKGROUND: Gastric bypass (GBP) is one of the most effective surgical procedures to treat morbid obesity and the related comorbidities. This study aimed at identifying preoperative predictors of successful weight loss and type 2 diabetes mellitus (T2DM) remission 1 year after GBP. METHODS: Prospective longitudinal study of 771 patients who underwent GBP was performed at four Italian centres between November 2011 and May 2013 with 1-year follow-up. Preoperative anthropometric, metabolic and social parameters, the surgical technique and the previous failed bariatric procedures were analyzed. Weight, the body mass index (BMI), the percentage of excess weight lost (% EWL), the percentage of excess BMI lost (% BMIL) and glycated haemoglobin (HbA1c) were recorded at follow-up. RESULTS: Univariate and multivariate analysis showed that BMI <50 kg/m2 (p\u2009=\u20090.006) and dyslipidaemia (p\u2009=\u20090.05) were predictive factors of successful weight loss. Multivariate analysis of surgical technique showed significant weight loss in patients with a small gastric pouch (p\u2009<\u20090.001); the lengths of alimentary and biliary loops showed no statistical significance. All diabetic patients had a significant reduction of HbA1c (p\u2009<\u20090.001) after surgery. BMI\u2009 65\u200950 kg/m2 (p\u2009=\u20090.02) and low level of preoperative HbA1c (p\u2009<\u20090.01) were independent risk factors of T2DM remission after surgery. CONCLUSIONS: This study provides a useful tool for making more accurate predictions of best results in terms of weight loss and metabolic improvement

The Exploration and Practice of Party Member of College Students rdquo;Recognizing Position and Taking Responsibility for a Model”

AbstractNowadays, it has become more important to strengthen the education, management and training work of the party members of college students. Our school has carried out the party members of college students. rdquo;recognizing position and taking responsibility for a model” activity for two years. And obtained some experience. The party members of college students rdquo;recognizing position and taking responsibility for a model” activity should set up scientific positions, define their responsibilities clearly and strengthen the management and assessment

Characterization of extracellular vesicles in osteoporotic patients compared to osteopenic and healthy controls

Extracellular vesicles (EVs) are mediators of a range of pathological conditions. However, their role in bone loss disease has not been well understood. In this study we characterized plasma EVs of 54 osteoporotic (OP) postmenopausal women compared to 48 osteopenic (OPN) and 44 healthy controls (CN), and we investigated their effects on osteoclasts and osteoblasts. We found no differences between the three groups in terms of anthropometric measurements and biochemical evaluation of serum calcium, phosphate, creatinine, PTH, 25-hydroxy vitamin D and bone biomarkers, except for an increase of CTX level in OP group. FACS analysis revealed that OP patients presented a significantly increased number of EVs and RANKL(+) EVs compared with both CN and OPN subjects. Total EVs are negatively associated with the lumbar spine T-score and femoral neck T-score. Only in the OPN patients we observed a positive association between the total number of EVs and RANKL(+) EVs with the serum RANKL. In vitro studies revealed that OP EVs supported osteoclastogenesis of healthy donor peripheral blood mononuclear cells at the same level observed following RANKL and M-CSF treatment, reduced the ability of mesenchymal stem cells to differentiate into osteoblasts, while inducing an increase of OSTERIX and RANKL expression in mature osteoblasts. The analysis of miRNome revealed that miR-1246 and miR-1224-5p were the most upregulated and downregulated in OP EVs; the modulated EV-miRNAs in OP and OPN compared to CN are related to osteoclast differentiation, interleukin-13 production and regulation of canonical WNT pathway. A proteomic comparison between OPN and CN EVs evidenced a decrease in fibrinogen, vitronectin, and clusterin and an increase in coagulation factors and apolipoprotein, which was also upregulated in OP EVs. Interestingly, an increase in RANKL(+) EVs and exosomal miR-1246 was also observed in samples from patients affected by Gorham-Stout disease, suggesting that EVs could be good candidate as bone loss disease biomarkers. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Assessing a measure for Quality of Life in patients with severe Alopecia Areata: a multicentric Italian study

Objective: The prevalence of anxiety and depression in patients diagnosed with Alopecia Areata (AA) is very high and this significant burden of psychological symptoms threatens the Health-Related Quality of Life (HRQoL) of affected patients. Indeed, AA often does not produce significant physical symptoms, but it nonetheless disrupts many areas of mental health. Clinical assessment of disease severity may not reliably predict patient's HRQoL, nor may it predict the patient's perception of illness. For this reason, considerable effort has been made to apply and develop measures that consider patient's perception and assess the HRQoL of individuals affected by AA. The aim of this multicentric study was to provide the Italian version of the Skindex-16AA and to evaluate its psychometric properties in a clinical sample of consecutive patients with moderate-to-severe AA. Methods: This is a longitudinal, multicenter, observational study. Patients returned for follow-up visits at 4-, 12-, and 24-weeks. The analyses of the current work aimed to confirm the factorial structure of the Skindex-16AA. In the case of non-fit, an alternative structure for the model was proposed, using an Exploratory Graph Analysis and the Bayesian approach. Results: The sample was composed of 106 patients with AA. Alopecia Universalis was the most frequently diagnosed type of alopecia at all time points. The analyses on the Skindex-16AA revealed that a two-factor structure with eight items fit the data best (Bayesian Posterior Predictive Checking using 95% Confidence Interval for the Difference Between the Observed and the Replicated Chi-Square values = −6.246/56.395, Posterior Predictive P-value = 0.06), and reported satisfactory psychometric properties (i.e., internal consistency and convergent validity). Conclusion: The Skindex-8AA demonstrated optimal psychometric properties (i.e., convergent and construct validity, and test-retest reliability) measured in a sample of patients with AA, that may suggest that it is an appropriate tool to measure the HRQoL in AA patients. However, further studies are needed in order to confirm and tested other psychometric features of this tool