13 research outputs found

    «Une belle infidèle». La traduction de l'Essai sur l'homme par l'abbé du Resnel

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    Zanconato Alessandro. «Une belle infidèle». La traduction de l'Essai sur l'homme par l'abbé du Resnel. In: Dix-huitième Siècle, n°37, 2005. Politiques et cultures des Lumières. pp. 561-575

    La dispute du fatalisme entre 1730-1760 en France

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    NANTERRE-BU PARIS10 (920502102) / SudocSudocFranceItalyFRI

    Vaginal birth after caesarean section: a multicentre study on prognostic factors and feasibility

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    Purpose: Vaginal birth after caesarean (VBAC) is an option to avoid major abdominal surgery and many consequences related to repeated caesarean delivery. In the last years, many efforts have been made to increase the number of patients attempting trial of labour after caesarean (TOLAC). The aim of our study was to identify the most important factors associated with the success of VBAC. Methods: A retrospective study was conducted in two Italian referral centres. Subjects included were singleton and morphologically normal pregnancy with previous C-section. Subjects with an inter-pregnancy interval shorter than 18 months, a large for gestational age baby, a pregnancy complicated with gestational diabetes and a previous unclassified uterine scar were excluded. The characteristics of the subjects were compared and a logistic regression was performed to evaluate variables associated with successful VBAC. Results: Of the 300 patients included, 224 (74.7%) achieved VBAC while 76 (25.3%) underwent C-section after failed TOLAC. The number of previous C-sections was not significantly associated with the success of TOLAC. Factors positively associated with achievement of VBAC were previous vaginal delivery (OR of 6.88 for one and 9.68 for more than one) and oxytocin implementation (OR 3.32). No maternal and neonatal adverse events occurred. Conclusion: Our results show that attempting VBAC is a feasible option in referral centres after adequate evaluation of the potential factors affecting the probability of success. A careful record of obstetrical history and management of labour can provide clinicians useful information to counsel women before and during labour

    The Role of Computed Tomography Colonography in Detecting Bowel Involvement in Women With Deep Infiltrating Endometriosis: Comparison With Clinical History, Serum Ca125, and Transvaginal Sonography

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    Objective: We wanted to assess the diagnostic value of computed tomographic colonography (CTC) in recognizing bowel endometriosis in comparison with serum Ca125, transvaginal sonography (TVS), and presence of intestinal symptoms. Methods: We included in this study 92 women undergoing surgery for symptomatic DiE. Preoperative evaluation included clinical history, Ca125 serum value, and TVS. CTC was performed in 37/92 patients (40.2%), and the results were compared to the other preoperative tools and to surgical exploration, considered the clinical reference standard. Results: Surgery confirmed bowel endometriosis in 49/92 subjects (53.3%). Presence of intestinal symptoms, serum Ca125 values, and TVS were significantly correlated to intestinal involvement, but CTC had the highest accuracy in detecting bowel endometriosis with a sensitivity of 68%, a specificity of 67%, a PPVof 81%, and a NPVof 50%(P = 0.04). Conclusions: CTC proved to be an accurate and low invasive imaging technique to detect DiE of the bowel and compared favorably with clinical evaluation, serum Ca125 determination, and TVS

    Broadly Applicable Hydrogel Fabrication Procedures Guided by YAP/TAZ-Activity Reveal Stiffness, Adhesiveness, and Nuclear Projected Area as Checkpoints for Mechanosensing

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    Mechanical signals are pivotal ingredients in how cells perceive and respond to their microenvironments, and to synthetic biomaterials that mimic them. In spite of increasing interest in mechanobiology, probing the effects of physical cues on cell behavior remains challenging for a cell biology laboratory without experience in fabrication of biocompatible materials. Hydrogels are ideal biomaterials recapitulating the physical cues that natural Extracellular Matrices (ECM) delivers to cells. Here we streamlined protocols for the synthesis and functionalization of cell adhesive Polyacrylamide-based (PAA-OH) and fully-defined Polyethyleneglycol-based (PEG-RGD) hydrogels tuned at various rigidities for mechanobiology experiments, from 0.3 to >10kPa. We investigated the mechanosignaling properties of these hydrogels in distinct cell types by monitoring the activation state of YAP/TAZ. By independently modulating substrate stiffness and adhesiveness, we found that although ECM stiffness represents an overarching mechanical signal, the density of adhesive sites does impact on cellular mechanosignaling at least at intermediate rigidity values, corresponding to normal and pathological states of living tissues. Using these tools, we found that YAP/TAZ nuclear accumulation occurs when the projected area of the nucleus surpasses a critical threshold of approximatively 150 ÎĽm(2). This work suggests the existence of distinct checkpoints for cellular mechanosensing

    Ewing's sarcoma in a young man mimicking lateral elbow pain: A case report with 2 years follow-up

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    Background and purpose: Lateral elbow pain represents a common musculoskeletal disorder, mostly non-specific and benign. In rare cases, it can be the first symptom of a severe disease such as Ewing's sarcoma (ES). ES is the second most common primary malignant bone tumor in the young population, with a high probability of an unfavourable prognosis. Case presentation: This case report presents the history of a young man presenting to the physical therapist with a diagnosis of "epicondylitis" in the right elbow, which was later revealed to be an aggressive ES of the ulna. Findings raising clinical doubts were (a) constant pain even at night and not dependent on load, (b) significant loss of function, (c) patient's young age, and (d) a palpable mass in the elbow. Results: After diagnosis, the patient received medical (chemotherapy, radiotherapy and surgery) and a rehabilitation program. After treatment, the patient improved elbow function, decreased disability and returned to social participation, maintaining positive outcomes at the 2-year follow-up. Discussion: In summary, this case report emphasizes the importance of differential diagnosis and screening for referral of red flags in physical therapy. Moreover, it describes the rehabilitation of a patient with ES, enriching the scientific literature in the field

    YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING

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    Ageing is intimately connected to the induction of cell senescence(1,2), but why this is so remains poorly understood. A key challenge isthe identification of pathways that normally suppress senescence, are lost during ageing and are functionally relevant to oppose ageing(3). Here we connected the structural and functional decline of ageing tissues to attenuated function of the master effectors of cellular mechanosignalling YAP and TAZ. YAP/TAZ activity declines during physiological ageing in stromal cells, and mimicking such decline through genetic inactivation of YAP/TAZ in these cells leads to accelerated ageing. Conversely, sustaining YAP function rejuvenates old cells and opposes the emergence of ageing-related traits associated with either physiological ageing or accelerated ageing triggered by a mechano-defective extracellular matrix. Ageing traits induced by inactivation of YAP/TAZ are preceded by induction oftissue senescence. This occurs because YAP/TAZ mechanotransduction suppresses cGAS-STING signalling, tothe extent that inhibition of STING preventstissue senescence and premature ageing-related tissue degeneration after YAP/TAZ inactivation. Mechanistically, YAP/TAZ-mediated control of cGAS-STING signalling relies on the unexpected role of YAP/TAZ in preserving nuclear envelope integrity, at least in part through direct transcriptional regulation of lamin Bland ACTR2, the latter of which is involved in building the peri-nuclear actin cap. The findings demonstrate that declining YAP/TAZ mechanotransduction drives ageing by unleashing cGAS-STING signalling, a pillar of innate immunity. Thus, sustaining YAP/TAZ mechanosignalling or inhibiting STING may represent promising approaches for limiting senescence-associated inflammation and improving healthy ageing

    YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING

    No full text
    Ageing is intimately connected to the induction of cell senescence(1,2), but why this is so remains poorly understood. A key challenge isthe identification of pathways that normally suppress senescence, are lost during ageing and are functionally relevant to oppose ageing(3). Here we connected the structural and functional decline of ageing tissues to attenuated function of the master effectors of cellular mechanosignalling YAP and TAZ. YAP/TAZ activity declines during physiological ageing in stromal cells, and mimicking such decline through genetic inactivation of YAP/TAZ in these cells leads to accelerated ageing. Conversely, sustaining YAP function rejuvenates old cells and opposes the emergence of ageing-related traits associated with either physiological ageing or accelerated ageing triggered by a mechano-defective extracellular matrix. Ageing traits induced by inactivation of YAP/TAZ are preceded by induction oftissue senescence. This occurs because YAP/TAZ mechanotransduction suppresses cGAS-STING signalling, tothe extent that inhibition of STING preventstissue senescence and premature ageing-related tissue degeneration after YAP/TAZ inactivation. Mechanistically, YAP/TAZ-mediated control of cGAS-STING signalling relies on the unexpected role of YAP/TAZ in preserving nuclear envelope integrity, at least in part through direct transcriptional regulation of lamin Bland ACTR2, the latter of which is involved in building the peri-nuclear actin cap. The findings demonstrate that declining YAP/TAZ mechanotransduction drives ageing by unleashing cGAS-STING signalling, a pillar of innate immunity. Thus, sustaining YAP/TAZ mechanosignalling or inhibiting STING may represent promising approaches for limiting senescence-associated inflammation and improving healthy ageing

    The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ

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    nactivation of ARID1A and other components of the nuclear SWI/SNF protein complex occurs at very high frequencies in a variety of human malignancies, suggesting a widespread role for the SWI/SNF complex in tumour suppression1. However, the underlying mechanisms remain poorly understood. Here we show that ARID1A-containing SWI/SNF complex (ARID1A-SWI/SNF) operates as an inhibitor of the pro-oncogenic transcriptional coactivators YAP and TAZ2. Using a combination of gain- and loss-of-function approaches in several cellular contexts, we show that YAP/TAZ are necessary to induce the effects of the inactivation of the SWI/SNF complex, such as cell proliferation, acquisition of stem cell-like traits and liver tumorigenesis. We found that YAP/TAZ form a complex with SWI/SNF; this interaction is mediated by ARID1A and is alternative to the association of YAP/TAZ with the DNA-binding platform TEAD. Cellular mechanotransduction regulates the association between ARID1A-SWI/SNF and YAP/TAZ. The inhibitory interaction of ARID1A-SWI/SNF and YAP/TAZ is predominant in cells that experience low mechanical signalling, in which loss of ARID1A rescues the association between YAP/TAZ and TEAD. At high mechanical stress, nuclear F-actin binds to ARID1A-SWI/SNF, thereby preventing the formation of the ARID1A-SWI/SNF-YAP/TAZ complex, in favour of an association between TEAD and YAP/TAZ. We propose that a dual requirement must be met to fully enable the YAP/TAZ responses: promotion of nuclear accumulation of YAP/TAZ, for example, by loss of Hippo signalling, and inhibition of ARID1A-SWI/SNF, which can occur either through genetic inactivation or because of increased cell mechanics. This study offers a molecular framework in which mechanical signals that emerge at the tissue level together with genetic lesions activate YAP/TAZ to induce cell plasticity and tumorigenesis
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