Effects of ospemifene on overactive bladder in postmenopausal women with vulvovaginal atrophy.

OBJECTIVE: Overactive bladder (OAB) is a complex and multifactorial syndrome associated with urinary frequency, urgency and incontinence. The menopause-associated hormonal changes play a role in the development of this condition. Vaginal estrogens are effective in improving OAB in postmenopausal women (PMW) with vulvovaginal atrophy (VVA). Ospemifene is a selective estrogen receptor modulator licensed for the treatment of VVA. This study aimed to evaluate the effects of ospemifene on OAB symptoms in PMW with VVA. METHODS: Forty PMW suffering from OAB and VVA received oral ospemifene (60 mg/day) for 12 weeks. All patients were assessed with a urodynamic study, a 3-day bladder diary and validated questionnaires (International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form [ICIQ-UI SF] and International Consultation on Incontinence Questionnaire - Overactive Bladder [ICIQ-OAB]) at enrollment and at the end of the study. RESULTS: Cytometric capacity, bladder compliance and verbal sensory threshold responses during bladder filling were improved after treatment. The voiding diary showed a significant reduction of daily voids, urge urinary incontinence episodes and nocturnal events. The median overall scores of the ICIQ-UI and ICIQ-OAB were also significantly improved. CONCLUSIONS: Our study suggest that treatment with ospemifene in PMW suffering from OAB is associated with a reduction of OAB symptoms due to a decreased bladder sensitivity and with an improvement in quality of life.

Single feature constrained manual registration method for Augmented Reality applications in gynecological laparoscopic interventions.

Augmented Reality (AR) can avoid some of the drawbacks of Minimally Invasive Surgery and may provide opportunities for developing innovative tools to assist surgeons. In laparoscopic surgery, the achievement of easy and sufficiently accurate registration is an open challenge. This is particularly true in procedures, such as laparoscopic abdominal Sacro-Colpopexy, where there is a lack of a sufficient number of visible anatomical landmarks to be used as a reference for registration. In an attempt to address the above limitations, we developed and preliminarily testes a constrained manual procedure based on the identification of a single anatomical landmark in the laparoscopic images, and the intraoperative measurement of the laparoscope orientation. Tests in a rigid in-vitro environment show good accuracy (median error 2.4 mm obtained in about 4 min) and good preliminary feedback from the technical staff who tested the system. Further experimentation in a more realistic environment is needed to validate these positive results. Clinical Relevance - This paper provides a new registration method for the development of AR educational videos and AR-based navigation systems for laparoscopic interventions.

Menopause, aging and the failing pelvic floor: a clinician's view.

The management of pelvic organ disorders is common and challenging work. Nowadays, midlife women are more active than they were in the past, and the development of pelvic organ prolapse (POP) disrupts quality of life and impairs social and personal activities. The aging process and hormonal changes have a role in influencing the structure and function of the lower urinary and genital tract. Correct diagnosis of pelvic organ disorders and the identification of women's symptoms are the hallmarks of tailored management. Treatment is multimodal and multidisciplinary; it requires competence in pelvic medicine and surgery. When conservative treatments fail, women with symptomatic POP are candidates for reconstructive surgery: the optimal management requires clinicians who are familiar with all of the available strategies and who are able to choose the best strategies in a tailored manner. Knowing and understanding the management of POP should be integrated into the practice of health-care professionals dealing in menopause.

Electroporation-based treatments in minimally invasive percutaneous, laparoscopy and endoscopy procedures for treatment of deep-seated tumors.

Electroporation (EP) techniques, used alone (Irreversible Electroporation, IRE) or in combination with anti-cancer drugs (Electrochemotherapy, ECT), have been shown to be effective in the treatment of several types of cancers. The efficacy of ECT and IRE is well demonstrated for the treatment of non-superficial tumor metastases, and it depends on the applied electrical parameters. Particularly, ECT is an effective local therapy that uses electroporation to enhance the cytotoxic effect of bleomycin or cisplatin injected intravenously or intratumorally. Pre-clinical investigations to test alternative anti-cancer drugs, explore new combinations of treatment modalities, and evaluate different sets of pulse protocols for effective tissue electroporation, are ongoing. Further ECT developments include the treatment of deep-seated tumors with percutaneous, laparoscopy, and endoscopy approaches, with the aim of establishing a less invasive approach. ECT is highly effective in the treatment of tumors of any histology, in minimizing the damage of critical normal tissue or organs, and in reducing pain and muscular contractions. This work describes the new technological advances in the field of ECT treatment for deep-seated tumors.

Cranberry, D-mannose and anti-inflammatory agents prevent lower urinary tract symptoms in women undergoing prolapse surgery.

Objective: We assessed the effect on lower urinary tract symptoms (LUTS) of a supplement containing cranberry, D-mannose and anti-inflammatory molecules in postmenopausal women undergoing surgery for cystocele.Study design: Forty postmenopausal women were randomized 1:1 to an active group receiving the nutritional supplement twice a day for 2 weeks starting from surgery, or to a control group receiving surgery only. Primary outcomes were the effectiveness in the postoperative LUTS and urinary tract infections (UTI). LUTS were investigated by a validated questionnaire (ICIQ-FLUTS) at baseline and at week 4. Secondary outcomes were the safety and tolerability of the supplement and other perioperative outcomes.Results: No significant differences were found in perioperative outcomes and in incidence of UTI. After surgery, women treated with the supplement experienced significantly better scores on the filling domain of the questionnaire. A non-significant decrease in voiding scores was also found. No adverse events were detected.Conclusion: The use of an oral supplement containing cranberry, D-mannose and anti-inflammatory molecules decreases the perception of LUTS in postmenopausal women after anterior colporraphy. Our data suggest that perioperative use of nutritional supplements may be useful in the management of postoperative LUTS.

Complementemia in pregnancies with antiphospholipid syndrome.

Prognosis of pregnancies in women with antiphospholipid syndrome has dramatically improved over the past two decades using conventional treatment with low molecular weight heparin and low-dose aspirin. However, despite this regimen, 10-15% of antiphospholipid syndrome patients experience pregnancy losses. Several studies have been performed in order to identify risk factors predictive of complications. Thrombosis has been generally accepted as the key pathogenetic mechanism underlying pregnancy morbidity. However, the thrombogenic state alone is not able to explain all the different mechanisms leading to pregnancy failure. In fact, emerging evidence shows that complement pathway could play an important role in mediating clinical events in antiphospholipid syndrome. However, the exact mechanism through which complement mediates antiphospholipid syndrome complications remains unknown. Low complement levels (C3 and C4) are associated with poor pregnancy outcome in women with antiphospholipid syndrome in different studies. Hypocomplementemia could be indicated as an early predictor of adverse pregnancy outcome, available at the beginning of pregnancy for starting, if necessary, additional treatment to conventional therapy. However, future studies need to better understand the impact of low complement level on antiphospholipid syndrome pregnancy outcome.

"My friend, the pain": does altered body awareness affect the valence of pain descriptors?

Background: Pain is a marker of bodily status, that despite being aversive under most conditions, may also be perceived as a positive experience. However, how bodily states represent, define, and interpret pain signals, and how these processes might be reflected in common language, remains unclear. Methods: Qualitative and quantitative methods were used to explore the relationship between bodily awareness, pain reactions, and descriptions. A list of pain-related terms was generated from open-ended interviews with persons with spinal cord injury (SCI), and 138 participants (persons with SCI, health professionals, and a healthy control group) rated each descriptor as representative of pain on a gradated scale. A lexical decision task was used to test the strength of the automatic association of the word "pain" with positive and negative concepts. The behavioral results were related to body awareness, experience of pain, and exposure to pain, by comparing the three groups. Results: Higher positive and lower negative pain descriptors, as well as slower response times when categorizing pain as an unpleasant experience were found in the SCI group. The effect was not modulated by either the time since the injury or the present pain intensity, but it was linked to the level of subjective bodily awareness. Compared with the SCI group, health experts and non-experts both associated more quickly the word "pain" and unpleasant in the lexical decision task. However, while health professionals attributed positive linguistic qualities to pain, pain was exclusively associated with negative descriptors in healthy controls group. Conclusions: These findings are discussed in terms of their theoretical and clinical implications. An awareness of bodily signals prominently affects both the sensory and linguistic responses in persons with SCI. Pain should be evaluated more broadly to understand and, by extension, to manage, experiences beyond its adverse side.

Delayed delivery of the second twin: Case report and literature review of diamniotic dichorionic twin pregnancy with very early preterm premature rupture of membranes.

In multiple pregnancies with threatened premature delivery or preterm premature rupture of membranes (pPROM) of a single sac, prolonging pregnancy after the delivery of the first baby may improve the chances of survival of the second baby. We report the delayed delivery of a second baby in a twin pregnancy with pPROM and very premature delivery of the first baby. This condition is exceptional and there are no validated medical protocols for its management; the scientific evidence is still controversial. In our case, after the birth of the first baby, pregnancy was continued for 29 days, with monitoring of maternal and fetal parameters, which enabled the delivery of the second baby with improved neonatal outcomes. This case supports the prolongation of the pregnancy of the second twin.

Oral dehydroepiandrosterone restores ß-endorphin response to OGTT in early and late postmenopause.

ß-endorphin is a neuropeptide involved in several brain functions: its plasma levels are higher in obese women and its release increases after oral glucose tolerance test (OGTT) in normal or obese women. The study included 46 healthy women and evaluated the effect of oral dehydroepiandrosterone [DHEA] (50 mg/day) in early postmenopausal women (50-55 years) both of normal weight (group A, n = 12, BMI = 22.1 ± 0.5) and overweight (group B, n = 12, BMI = 28.2 ± 0.5), and late postmenopausal women (60-65 years) both normal weight (group C, n = 11, BMI = 22.5 ± 0.6) and overweight (group D, n = 11, BMI = 27.9 ± 0.4) undergone OGTT, in order to investigate if DHEA could restore/modify the control of insulin and glucose secretion and ß-endorphin release in response to glucose load. The area under the curve (AUC) of OGTT evaluated plasma levels of different molecules. DHEA, DHEAS, and ß-endorphin plasma levels were lower in baseline conditions in older women than younger women. Considering the AUC of ß-endorphin response to OGTT, all groups showed a progressive significant increase after 3 and also after 6 months of treatment in comparison to baseline and 3 months of treatment.

Advances in surgical strategies for prolapse.

Pelvic floor dysfunctions are a complex condition in elderly women; pelvic organ prolapse, urinary or fecal incontinence, constipation, pelvic pain, and sexual dysfunction are common problems. The goal of surgical treatment is functional reconstruction with symptom management and repair of anatomic defects. The recent advancements in surgical treatment of pelvic floor dysfunction allow several good options for choosing the best surgery for each patient. The vaginal procedure is traditionally the gold standard approach for elderly patients, but abdominal surgery is increasing as a mini-invasive approach and the robotic approach is gaining acceptance for treatment of pelvic floor dysfunctions. In elderly individuals, a multitude of factors affects the final result of any reconstructive surgery such as postmenopausal or aging-associated changes in muscle tone and nerve function or changes in the function of the bladder or of the rectum: an understanding of the underlining functional status of pelvic organs is very important in aging women before proceeding to surgery. In this context, pelvic floor dysfunction, particularly in elderly women, should be addressed in a multidisciplinary manner and, at the forefront, centers for surgical planning could be helpful to perform safer, patient-tailored surgery.

A medical device containing purified bovine colostrum (Monurelle Biogel) in the treatment of vulvovaginal atrophy in postmenopausal women: Retrospective analysis of urinary symptoms, sexual function, and quality of life.

OBJECTIVE: This study assessed the effectiveness and safety of a medical device containing purified bovine colostrum (Monurelle Biogel; Zambon, Bresso, Italy) in improving vulvovaginal atrophy (VVA), sexual function, urinary symptoms, and quality of life (QoL) in postmenopausal women. METHODS: In all, 172 postmenopausal women with VVA were included in the study. All women were treated with vaginal Monurelle Biogel daily for 12 weeks. Patients underwent clinical examinations, completed a 3-day voiding diary, and had VVA graded using the Vaginal Health Index (VHI) at baseline and 12 weeks. Patients also completed the Female Sexual Function Index (FSFI), overactive bladder questionnaire (OAB-Q), and the Urogenital Distress Inventory (UDI-6), among others. RESULTS: After 12 weeks, there were significant increases in mean (± SD) VHI (12.53 ± 3.67 vs. 19.31 ± 3.49; P < .0001), the number of patients engaging in regular sexual activity 102 (59.3%) vs. 144 (83.7%), and in the total FSFI score (21.64 ± 2.99 vs. 28.16 ± 1.93; P < .0001) compared with baseline. In addition, there were significant reductions in the mean number of 24-hour voids (9.57 ± 2.12 vs. 7.13 ± 1.22; P < .0001), urgent micturition episodes per 24 hours (1.75 ± 0.76 vs. 1.14 ± 0.87; P = .001), nocturia episodes (1.58 ± 0.85 vs. 0.97 ± 1.18; P = .0002), and urinary incontinence episodes per 24 hours (0.74 ± 0.59 vs. 0.28 ± 0.52; P = .003). Finally, after 12 weeks treatment, there were significant differences in UDI-6 (7.85 ± 0.81 vs. 5.56 ± 1.40), OAB-Q symptom (53.60 ± 12.57 vs. 22.08 ± 9.63), and OAB-Q health-related QoL (21.75 ± 8.51 vs. 69.34 ± 14.59) scores compared with baseline (P < .0001 for all). The Patient Impression of Global Improvement scale revealed global improvement in 143 women (83.14%). CONCLUSIONS: Monurelle Biogel is an effective treatment for VVA in postmenopausal women, improving sexual life, urinary symptoms, and QoL.

Optimizing quality of life through sex steroids by their effects on neurotransmitters.

Menopause-related symptoms such as hot flushes, night sweats, weight gain, and decreased sexual functioning all have negative impacts on quality of life and affect daily activities such as sleep, work, and leisure activities. During the menopause transition, neurotransmitters, neuropeptides, and neurosteroids undergo important changes as a consequence of the failure of gonadal hormone production, at a time when many central nervous system activities deteriorate. Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination, and other important mechanisms of neural plasticity. Knowledge of interactions between sex steroid hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA, and glutamate, will give women and health providers an important tool for improving their health and well-being. From the concept of neurosteroids derives another treatment strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach has so far been hampered by lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by the peripheral gland or with exogenous steroids. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neurosteroids in postmenopausal women and their impact on quality of life.

Diagnosis and laparoscopic management of a 5-week ectopic pregnancy in a rudimentary uterine horn: A case report.

Uterine anomalies result from the failure of complete fusion of the Müllerian ducts during embryogenesis. A unicornuate uterus with a rudimentary horn is the rarest anomaly and results from the failure of one of the Müllerian ducts to develop completely and an incomplete fusion with the contralateral side. Diagnosis and surgical management of a 5-week ectopic pregnancy in a non-communicating rudimentary horn in an 18-year-old nulliparous woman in whom this congenital uterine anomaly was previously unknown are described.

Brain abscesses in children: an Italian multicentre study.

Brain abscess is uncommon in paediatric population, but of clinical importance because of significant long-term morbidity and mortality. In this multicentre study, promoted by the Italian Society for Paediatric Infectious Diseases, we retrospectively collected patients aged 0-18 years, with a diagnosis of 'brain abscess'. Seventy-nine children were included; the median age was 8·75 years. As predisposing factor, 44 children had preceding infections. The Gram-positive cocci were mostly isolated (27 cases). Sixty (76%) children underwent a surgical intervention. Intravenous antibiotic therapy was administered in all patients, then switched to oral treatment. Clinical sequelae were recorded in 31 (39·2%) children. Twenty-one of them had a single sequela, of which, the most represented, was epilepsy in nine of them. This study focus the attention on the need to have standardized national guidelines or adequate recommendations on type and duration of antibiotic treatment.

Neural foundation of human moral reasoning: an ALE meta-analysis about the role of personal perspective.

Moral sense is defined as a feeling of the rightness or wrongness of an action that knowingly causes harm to people other than the agent. The large amount of data collected over the past decade allows drawing some definite conclusions about the neurobiological foundations of moral reasoning as well as a systematic investigation of methodological variables during fMRI studies. Here, we verified the existence of converging and consistent evidence in the current literature by means of a meta-analysis of fMRI studies of moral reasoning, using activation likelihood estimation meta-analysis. We also tested for a possible neural segregation as function of the perspective used during moral reasoning i.e., first or third person perspectives. Results demonstrate the existence of a wide network of areas underpinning moral reasoning, including orbitofrontal cortex, insula, amygdala, anterior cingulate cortex as well as precuneus and posterior cingulate cortex. Within this network we found a neural segregation as a function of the personal perspective, with 1PP eliciting higher activation in the bilateral insula and superior temporal gyrus as well as in the anterior cingulate cortex, lingual and fusiform gyri, middle temporal gyrus and precentral gyrus in the left hemisphere, and 3PP eliciting higher activation in the bilateral amygdala, the posterior cingulate cortex, insula and supramarginal gyrus in the left hemisphere as well as the medial and ventromedial prefrontal cortex in the right hemisphere. These results shed some more light on the contribution of these areas to moral reasoning, strongly supporting a functional specialization as a function of the perspective used during moral reasoning.

Health Technology Assessment: introducing a vacuum-based preservation system for biological materials in the anatomic pathology workflow.

INTRODUCTION: The objective of this work is to assess the implementation of a newly introduced medical equipment technology for the vacuum-based preservation of biological materials within an Anatomic Pathology service. METHODS: The approach selected for the analysis is the Health Technology Assessment (HTA ), a comprehensive evaluation method based on relevant scientific evidence and designed to support healthcare decision makers in purchasing, replacing or disposing of technologies. The analysis focused on specific domains such as Technology, Organization, Safety and Economy. RESULTS: The study proves that the use of such technology ensures the biological specimen to be suitably preserved (up to 72 hours), both reducing the amount of fixative being employed in the diagnostic process (30% to 55%) and resulting, in the particular context under examination, in savings of 93%. DISCUSSION: The HTA reported no significant drawbacks related to the use of the technology being examined. Nonetheless, the workflow for managing the transfer of biological materials from the Operating Room to the Anatomic Pathology department needs to be redefined - in terms of handling, processing, storage and disposal. Other elements concerned the monitoring of storage temperature, fresh tissue handling and especially fixative amount reduction, which positively impacts on the operators' safety with regard to chemical hazards.

Where does brain neural activation in aesthetic responses to visual art occur? Meta-analytic evidence from neuroimaging studies.

Here we aimed at finding the neural correlates of the general aspect of visual aesthetic experience (VAE) and those more strictly correlated with the content of the artworks. We applied a general activation likelihood estimation (ALE) meta-analysis to 47 fMRI experiments described in 14 published studies. We also performed four separate ALE analyses in order to identify the neural substrates of reactions to specific categories of artworks, namely portraits, representation of real-world-visual-scenes, abstract paintings, and body sculptures. The general ALE revealed that VAE relies on a bilateral network of areas, and the individual ALE analyses revealed different maximal activation for the artworks' categories as function of their content. Specifically, different content-dependent areas of the ventral visual stream are involved in VAE, but a few additional brain areas are involved as well. Thus, aesthetic-related neural responses to art recruit widely distributed networks in both hemispheres including content-dependent brain areas of the ventral visual stream. Together, the results suggest that aesthetic responses are not independent of sensory, perceptual, and cognitive processes.

Selective steroid receptor modulators in reproductive medicine.

A key step forward in the treatment of hormone-dependent diseases has been made since the discovery of tissue-specific steroid receptor modulators (SRMs), or receptor ligands that elicit agonistic or antagonistic effects in a cell- and tissue-dependent manner. In reproductive medicine, selective estrogen receptors modulators (SERMs) and selective progesterone receptors modulator (SPRMs) were discovered and developed since the 1970s. SERMs were first released for the treatment of infertility and later developed in areas such as osteoporosis prevention and breast cancer treatment. The later discovery of SPRMs has provided molecules active on the inhibition of ovulation, on the endometrium and on leiomyoma cells, which are currently being developed for their antiproliferative effects in breast cancer and endometriosis. New molecules and new routes of administration of SERMs and SPRMs are in development for cancer treatment, long-term contraception and endometriosis. Based on the future advancements on the understanding of the mechanisms of action of these compounds, it is to be expected that future SRMs will emerge for newer indications.