53 research outputs found

    Uterine and ovarian changes during testosterone administration in young female-to-male transsexuals

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    Abstract Objective Female-to-male transition remains a specific clinical indication for long-term testosterone administration. There is a limited number of studies dealing with the effect of androgen treatment on their female receptive targets (mainly breast and uterus) and the knowledge in this field is scarce and, sometimes, contradictory. Materials and Methods We performed a prospective study including 12 patients aged between 20 years and 32 years, with a diagnosis of gender dysphoria, treated with parenteral testosterone administration before sexual reassignment surgery. Results Endometrial histology revealed the presence of active endometrium in 10 cases and secretive endometrium in two cases. Multifollicular ovaries were observed in all cases of active endometrium, while corpus luteum was present in the two cases of secretory endometrium. Fibroids or hypertrophic myometrium were observed in 58% of the patients. Estrogen receptor was very high (59%) in the endometrial epithelial cells and low (17%) in the myometrium. Androgen receptor expression was modest in endometrial epithelial cells (24%) and sustained in myometrium (69%). Ki67 expression is steadily present in all uterine compartments, varying from 8% in epithelial endometrium to 2% in the myometrium. Conclusion Our data suggest that long-term testosterone administration to female-to-male patients during reproductive age induces a low proliferative active endometrium, associated with some hypertrophic myometrial changes

    Volcanic jets, plumes, and collapsing fountains: evidence from large-scale experiments, with particular emphasis on the entrainment rate

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    The source conditions of volcanic plumes and collapsing fountains are investigated by means of large-scale experiments. In the experiments, gas-particle jets issuing from a cylindrical conduit are forced into the atmosphere at different mass flow rates. Dense jets (high particle volumetric concentration, e.g., C 0 > 0.01) generate collapsing fountains, whose height scales with the squared exit velocity. This is consistent with Bernoulli's equation, which is a good approximation if air entrainment is negligible. In this case, kinetic energy is transformed into potential energy without any significant loss by friction with the atmosphere. The dense collapsing fountain, on hitting the ground, generates an intense shear flow similar to a pyroclastic density current. Dilute hot jets (low particle volumetric concentration, e.g., C 0 3). © 2014 Springer-Verlag Berlin Heidelberg

    Upgrading Treatment and Molecular Diagnosis in Endometrial Cancer-Driving New Tools for Endometrial Preservation?

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    One emerging problem for onco-gynecologists is the incidence of premenopausal patients under 40 years of age diagnosed with stage I Endometrial Cancer (EC) who want to preserve their fertility. Our review aims to define a primary risk assessment that can help fertility experts and onco-gynecologists tailor personalized treatment and fertility-preserving strategies for fertile patients wishing to have children. We confirm that risk factors such as myometrial invasion and The International Federation of Gynecology and Obstetrics (FIGO) staging should be integrated into the novel molecular classification provided by The Cancer Genome Atlas (TCGA). We also corroborate the influence of classical risk factors such as obesity, Polycystic ovarian syndrome (PCOS), and diabetes mellitus to assess fertility outcomes. The fertility preservation options are inadequately discussed with women with a diagnosis of gynecological cancer. A multidisciplinary team of gynecologists, oncologists, and fertility specialists could increase patient satisfaction and improve fertility outcomes. The incidence and death rates of endometrial cancer are rising globally. International guidelines recommend radical hysterectomy and bilateral salpingo-oophorectomy as the standard of care for this cancer; however, fertility-sparing alternatives should be tailored to motivated women of reproductive age, establishing an appropriate cost-benefit balance between childbearing desire and cancer risk. New molecular classifications such as that of TCGA provide a robust supplementary risk assessment tool that can tailor the treatment options to the patient's needs, curtail over- and under-treatment, and contribute to the spread of fertility-preserving strategies

    In Vivo Functional Platform Targeting Patient-Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer

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    SummaryCurrent treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential for PDAC maintenance. We developed an unbiased and in vivo target discovery approach to identify molecular vulnerabilities in low-passage and patient-derived PDAC xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of the COMPASS histone H3 Lys4 (H3K4) MLL (1–4) methyltransferase complex, as a top tumor maintenance hit required across multiple human and mouse tumors. Mechanistically, WDR5 functions to sustain proper execution of DNA replication in PDAC cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR5. We indeed demonstrate that interaction with c-Myc is critical for this function. By showing that ATR inhibition mimicked the effects of WDR5 suppression, these data provide rationale to test ATR and WDR5 inhibitors for activity in this disease

    Aerodynamics of stratovolcanoes during multiphase processes

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    Pyroclastic density currents (PDCs) are gas-particle flows generated during explosive eruptions, which are often erupted over the flanks of stratovolcanoes. These volcanoes may have different shapes, which can affect the flow aerodynamics and hence the depositional processes. Here, multiphase numerical simulations are carried out in order to define semiquantitative relationships among the PDC behavior, particle response, and deposit formation. Three stratovolcano shapes are used: straight, convex and concave, and, by means of numerical simulations, their effects both on the flow structure and depositional processes are highlighted. The current starts moving as a homogeneous flow, and then it rapidly evolves to a turbulent boundary layer moving in contact with the ground, overlaid by a companion wake region. Results show that thin boundary layers produce thick deposits of massive layers, whereas thick boundary layers produce thin laminated deposits. Moreover, concave wake regions would produce thick massive deposits of fine ash, whereas convex wake regions would produce thin ash deposits. Copyright 2012 by the American Geophysical Union.Peer Reviewe

    Single coronary artery originating from right sinus. Role of MDCT and a review of literature

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    SCA from the right sinus is the rarest coronary anomaly. We describe 2 cases: 1 with SCA type-1RI; 2 with SCA type-2RII-A. Appropriate and successful treatment (CABG in case-1; PTCA in case-2) was chosen relying on accurate morphological description provided by MDCT, in order to recognize all the possible mechanisms of myocardial ischemia

    The entrainment rate of non Boussinesq hazardous geophysical gas-particle flows: an experimental model with application to pyroclstic density currents.

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    The entrainment rate of pyroclastic density currents is investigated by large-scale experiments. The ground flows are initiated by the impact on the terrain of a dense gas-particle fountain issuing from a cylindrical conduit, similarly to natural volcanic events. On impact, the excess density with respect to the surrounding atmosphere was up to 11.6 kg/m3, making the currents non-Boussinesq. A power law model of the entrainment rate is developed, which is similar to that proposed for snow avalanches by Ancey (2004, https://doi.org/10.1029/2003JF000052) and is verified for the Richardson's number range between 0.25 and 5.95. Rapid changes of the entrainment are caused by (i) strong accelerations at the fountain impact on the ground; (ii) break in slope; and (iii) topographic obstacles. Such changes, together with the sedimentation rate, influence flow mobility. The use of the power law is suggested for modeling the motion of unsteady hazardous geophysical mass flows such as pyroclastic density currents and snow avalanches

    A discriminatory diagram of massive versus stratified deposits based on the sedimentation and bedload transportation rates. Experimental investigation and application to pyroclastic density currents

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    Dense gas‐particle jets similar to collapsing eruption columns were generated by large‐scale experiments. The column collapse resulted in a ground‐hugging current forming stratified layers with bedding similar to natural pyroclastic density current deposits. At the impact of the collapsing column on the ground, a thick, massive bed was formed due to a high sedimentation rate that dumped turbulence due to high clast concentration. Down‐current, flow expansion favoured turbulence and dilute gas‐particle current that formed thin rippled layers deposited under traction. Experiments fed with fine ash (median size 0·066 mm) formed deposits without tractional structures, because fine particles, as other sedimentary fine material, is cohesive and exposes a limited surface to the shear stress. Experimental outcomes show that massive beds are formed where the sedimentation rate per unit width Srw exceeds the bedload transportation rate Qb by two orders of magnitude. A lower ratio generates traction at the base of the flow and formation of shear structures that increase in wavelength and height with a decreasing flux. This study presents a diagram that provides a useful addition for facies analysis of pyroclastic density currents, provided that deposits representing sustained sedimentation can be identified in the field. In the diagram a decrease in the Srw/Qb ratio corresponds to an increase in bedform size. Application of the diagram for hazard assessment purposes allows the reconstruction of the mass eruption rate of the Agnano–Monte Spina eruption at Campi Flegrei, which is the main variable defining the intensity of past eruptions, and of the Bingham rheology of the massive underflow of the Mercato pyroclastic density current at Vesuvius.Peer reviewe
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