Measurement of the thickness of the urethrovaginal space in women with or without vaginal orgasm

Introduction. The physiology and anatomy of female sexual function are poorly understood. The differences in sexual function among women may be partly attributed to anatomical factors. Aim. The purpose of this study was to use ultrasonography to evaluate the anatomical variability of the urethrovaginal space in women with and without vaginal orgasm. Methods. Twenty healthy, neurologically intact volunteers were recruited from a population of women who were a part of a previous published study. All women underwent a complete urodynamic evaluation and those with clinical and urodynamic urinary incontinence, idiopathic detrusor overactivity, or micturition disorders, as well as postmenopausal women and those with sexual dysfunction were excluded. The reported experience of vaginal orgasm was investigated. Main Outcome Measure. The urethrovaginal space thickness as measured by ultrasound was chosen as the indicator of urogenital anatomical variability. Designated evaluators carried out the measurements in a blinded fashion. Results. The urethrovaginal space and distal, middle, and proximal urethrovaginal segments were thinner in women without vaginal orgasm. A direct correlation between the presence of vaginal orgasm and the thickness of urethrovaginal space was found. Women with a thicker urethrovaginal space were more likely to experience vaginal orgasm (r = 0.884; P = 0.015). A direct and significant correlation between the thickness of each urethrovaginal segment and the presence of vaginal orgasm was found, with the best correlation observed for the distal segment (r = 0.863; P < 0.0001). Interobserver agreement between the designated evaluators was excellent (r = 0.87; P < 0.001). Conclusions. The measurement of the space within the anterior vaginal wall by ultrasonography is a simple tool to explore anatomical variability of the human clitoris-urethrovaginal complex, also known as the G-spot, which can be correlated to the ability to experience the vaginally activated orgasm

The psychosexual profile of sexual assistants: an internet-based explorative study

Sexual assistance may have some aspects that resemble prostitution and others that might lead one to think of sexual assistants as similar to a group of subjects whose sexual object is disability (devotees). In this study, we investigate whether a rigorous selection and training process on the part of specialised organisations may reduce the risk of training subjects with an atypical sexual interest and behaviours resembling prostitution

Optimizing Nozzle Travel Time in Proton Therapy

Proton therapy is a cancer therapy that is more expensive than classical radiotherapy but that is considered the gold standard in several situations. Since there is also a limited amount of delivering facilities for this techniques, it is fundamental to increase the number of treated patients over time. The objective of this work is to offer an insight on the problem of the optimization of the part of the delivery time of a treatment plan that relates to the movements of the system. We denote it as the Nozzle Travel Time Problem (NTTP), in analogy with the Leaf Travel Time Problem (LTTP) in classical radiotherapy. In particular this work: (i) describes a mathematical model for the delivery system and formalize the optimization problem for finding the optimal sequence of movements of the system (nozzle and bed) that satisfies the covering of the prescribed irradiation directions; (ii) provides an optimization pipeline that solves the problem for instances with an amount of irradiation directions much greater than those usually employed in the clinical practice; (iii) reports preliminary results about the effects of employing two different resolution strategies within the aforementioned pipeline, that rely on an exact Traveling Salesman Problem (TSP) solver, Concorde, and an efficient Vehicle Routing Problem (VRP) heuristic, VROOM

The botanical drug PBI-05204, a supercritical CO2 extract of Nerium oleander, sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy in vitro and in vivo

Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na+/K+-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties. Herein, the therapeutic properties of PBI-05204, an extract from Nerium oleander containing the CG oleandrin already studied in phase I and II clinical trials for cancer patients, were investigated, in vitro and in vivo, against FN- and FP-RMS cancer models. PBI-05204 induced growth arrest in a concentration dependent manner, with FP-RMS being more sensitive than FN-RMS, by differently regulating cell cycle regulators and commonly upregulating cell cycle inhibitors p21Waf1/Cip1 and p27Cip1/Kip1. Furthermore, PBI-05204 concomitantly induced cell death on both RMS types and senescence in FN-RMS. Notably, PBI-05204 counteracted in vitro migration and invasion abilities and suppressed the formation of spheroids enriched in CD133+ cancer stem cells (CSCs). PBI-05204 sensitized both cell types to RT by improving the ability of RT to induce G2 growth arrest and counteracting the RT-induced activation of both Non‐Homologous End‐Joining and homologous recombination DSBs repair pathways. Finally, the antitumor and radio-sensitizing proprieties of PBI-05204 were confirmed in vivo. Notably, both in vitro and in vivo evidence confirmed the higher sensitivity to PBI-05204 of FP-RMS. Thus, PBI-05204 represents a valid radio-sensitizing agent for the treatment of RMS, including the intrinsically radio-resistant FP-RMS

NFATc1 Regulation of TRAIL Expression in Human Intestinal Cells

TNF-related apoptosis-inducing ligand (TRAIL; Apo2) has been shown to promote intestinal cell differentiation. Nuclear factor of activated T cells (NFAT) participates in the regulation of a variety of cellular processes, including differentiation. Here, we examined the role of NFAT in the regulation of TRAIL in human intestinal cells. Treatment with a combination of phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187 (Io) increased NFAT activation and TRAIL expression; pretreatment with the calcineurin inhibitor cyclosporine A (CsA), an antagonist of NFAT signaling, diminished NFAT activation and TRAIL induction. In addition, knockdown of NFATc1, NFATc2, NFATc3, and NFATc4 blocked PMA/Io increased TRAIL protein expression. Expression of NFATc1 activated TRAIL promoter activity and increased TRAIL mRNA and protein expression. Deletion of NFAT binding sites from the TRAIL promoter did not significantly abrogate NFATc1-increased TRAIL promoter activity, suggesting an indirect regulation of TRAIL expression by NFAT activation. Knockdown of NFATc1 increased Sp1 transcription factor binding to the TRAIL promoter and, importantly, inhibition of Sp1, by chemical inhibition or RNA interference, increased TRAIL expression. These studies identify a novel mechanism for TRAIL regulation by which activation of NFATc1 increases TRAIL expression through negative regulation of Sp1 binding to the TRAIL promoter