Cardiovascular Risk Perception and Knowledge among Italian Women: Lessons from IGENDA Protocol.

A multicenter, cross-sectional observational study (Italian GENder Differences in Awareness of Cardiovascular risk, IGENDA study) was carried out to evaluate the perception and knowledge of cardiovascular risk among Italian women. An anonymous questionnaire was completed by 4454 women (44.3 ± 14.1 years). The 70% of respondents correctly identified cardiovascular disease (CVD) as the leading cause of death. More than half of respondents quoted cancer as the greatest current and future health problem of women of same age. Sixty percent of interviewed women considered CVD as an almost exclusively male condition. Although respondents showed a good knowledge of the major cardiovascular risk factors, the presence of cardiovascular risk factors was not associated with higher odds of identifying CVD as the biggest cause of death. Less than 10% of respondents perceived themselves as being at high CVD risk, and the increased CVD risk perception was associated with ageing, higher frequency of cardiovascular risk factors and disease, and a poorer self-rated health status. The findings of this study highlight the low perception of cardiovascular risk in Italian women and suggest an urgent need to enhance knowledge and perception of CVD risk in women as a real health problem and not just as a as a life-threatening threat.

IGENDA protocol: gender differences in awareness, knowledge and perception of cardiovascular risk: an Italian multicenter study.

AIMS: Recent reports evidenced gender differences in the knowledge, perception and awareness of cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs). Despite the number of high-quality trials that attempted to establish the efficacy of different preventive interventions on CVDs, in the Italian scenario the differences by gender in awareness, knowledge and perception of CVD have not been addressed yet. So, the aims of this cross-sectional, observational and multicenter study will be to evaluate the gender differences in the awareness and perception of CVD risk, to assess the knowledge of CVD symptoms and preventive behaviors/barriers in men and women participating in this study, and to provide a national primary care approach for gender-oriented cardiovascular prevention strategies and therapy. METHODS: A self-administered questionnaire will be completed by 5000 consecutive Italian women and men aged 18-70 years. Moreover, a health questionnaire will be completed by the physicians. RESULTS: The present study will be the largest to be conducted in Italy, and probably in the European countries, to comprehensively demonstrate the current level of the knowledge, awareness and perception of CVRFs and CVD in both men and women. CONCLUSION: The present project could shed new light on the knowledge, awareness and perception of CVRFs and CVDs. If substantial differences will be detected by gender, the findings of this study may contribute to ultimately provide a new gender-oriented primary care approach inside the Italian healthcare system related to cardiovascular prevention and therapy strategies.

Modulation of Oxidative Stress by 17 ß-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro.

BACKGROUND/AIMS: estrogens and phytoestrogens exert hepatoprotection through mechanisms not clearly examined yet. Here, we investigated the protective effects exerted by 17ß-estradiol and genistein against oxidative stress in hepatocytes and hepatic stellate cells (HSCs) and the involvement of specific receptors and the intracellular signalling. METHODS: Huh7.5 and LX-2, alone or in co-culture with Huh7.5, were treated with 17ß-estradiol and genistein alone or in the presence of menadione and of estrogen receptors (ERs) and G protein-coupled-estrogenic-receptors (GPER) blockers. Cell viability, mitochondrial membrane potential and oxidant/antioxidant system were measured by specific kits. Western Blot was used for the analysis of Akt and p38-mitogen-activated-protein kinases (MAPK) activation and α-smooth-muscle actin expression. RESULTS: In Huh7.5, 17ß-estradiol and genistein prevented the effects of peroxidation by modulating Akt and p38MAPK activation. Similar antioxidant and protective findings were obtained in LX-2 of co-culture experiments, only. ERs and GPER blockers were able to prevent the effects of 17ß-estradiol and genistein. CONCLUSION: In Huh7.5 and LX-2, 17ß-estradiol and genistein counteract the effects of peroxidation through the involvement of ERs and GPER and by an intracellular signalling related to Akt and p38MAPK. As concerning LX-2, paracrine factors released by Huh7.5 play a key role in protection against oxidative stress.

Robotic-Assisted Conservative Excision of Retrocervical-Rectal Deep Infiltrating Endometriosis: A Case Series.

Deep infiltrating endometriosis (DIE) is a complex disease that impairs the quality of life and the fertility of women. Colorectal DIE accounts for 70% to 93% of all the intestinal endometriotic sites and frequently needs a surgical approach. However, the indications for the surgical management of this condition are still controversial. From March 2010 to June 2014, we scheduled 33 consecutive patients presenting with retrocervical-rectal DIE of any diameter not involving the mucosa nor producing rectal stenosis >50% for laparoscopic robotic-assisted nerve-sparing rectal nodulectomy (LRN). All patients were examined preoperatively, at 3 months and 6 months postoperatively, and yearly thereafter. Dysmenorrhea, dyschezia, dyspareunia, and dysuria were evaluated on a 10-point visual analog scale. Among the 33 enrolled patients, 31 (93.9%) fulfilled the selection criteria and were submitted to LRN. In 1 out of 31 available patients (3.2%), a segmental bowel resection was considered necessary for prudential purpose at the end of the nodulectomy procedure. No laparotomic conversion was performed in any case. A wide variety of associated surgical procedures were performed in 25 of 30 patients (83.3%). No intraoperative complications were observed. One grade 3b and 2 grade 1 postoperative complications were recorded. The mean larger axis of the excised nodules measured on the formalin-fixed specimen was 26.4 mm. We found significant improvements in patient symptoms at a 3-month follow-up which persisted over the time. We observed 2 (6.7%) recurrences of intestinal endometriosis and 1 (3.3%) recurrence of chronic pelvic pain without clinical and/or radiologic evidence of endometriotic lesions. The mean follow-up time was 27.6 months. We believe that LRN is feasible and safe and shows promising results in terms of radicality, anatomic recurrence rate, and pain recurrence rate for treating isolated retrocervical-rectal DIE not involving the mucosa, without limiting this procedure to nodules smaller than 3 cm.

Intraoperative radiotherapy in gynaecological and genito-urinary malignancies: focus on endometrial, cervical, renal, bladder and prostate cancers.

Intraoperative radiotherapy (IORT) refers to the delivery of a single radiation dose to a limited volume of tissue during a surgical procedure. A literature review was performed to analyze the role of IORT in gynaecological and genito-urinary cancer including endometrial, cervical, renal, bladder and prostate cancers.Literature search was performed by Pubmed and Scopus, using the words "intraoperative radiotherapy/IORT", "gynaecological cancer", "uterine/endometrial cancer", "cervical/cervix cancer", "renal/kidney cancer", "bladder cancer" and "prostate cancer". Forty-seven articles were selected from the search databases, analyzed and briefly described.Literature data show that IORT has been used to optimize local control rate in genito-urinary tumours mainly in retrospective studies. The results suggest that IORT could be advantageous in the setting of locally advanced and recurrent disease although further prospective trials are needed to confirm this findings.

Monomeric adiponectin increases cell viability in porcine aortic endothelial cells cultured in normal and high glucose conditions: Data on kinases activation.

We found that monomeric adiponectin was able to increase cell viability in porcine aortic endothelial cells (PAE) cultured both in normal and high glucose condition. Moreover, in normal glucose condition monomeric adiponectin increased p38MAPK, Akt, ERK1/2 and eNOS phosphorylation in a dose- and time-dependent way. Also in high glucose condition monomeric adiponectin increased eNOS and above kinases phosphorylation with similar patterns but at lower extent. For interpretation of the data presented in this article, please see the research article "Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions" (Grossini et al., in press) [1].

Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

AIMS: Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca(2+) transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. MAIN METHODS: PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca(2+)-ATPase pump inhibitors. The role of Na(+)/Ca(2+) exchanger was examined in experiments performed in zero Na(+) medium. NO release and intracellular Ca(2+) were measured through specific probes. KEY FINDINGS: In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca(2+)]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca(2+) mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na(+)/Ca(2+) exchanger and Ca(2+)-ATPase pump in restoring Ca(2+) was found. SIGNIFICANCE: Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca(2+) transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved.

Human Chorionic Gonadotropin Protects Vascular Endothelial Cells from Oxidative Stress by Apoptosis Inhibition, Cell Survival Signalling Activation and Mitochondrial Function Protection.

BACKGROUND/AIM: Previous reports have made it hypothetically possible that human chorionic gonadotropin (hCG) could protect against the onset of pregnancy-related pathological conditions by acting as an antioxidant. In the present study we planned to examine the effects of hCG against oxidative stress in human umbilical vein endothelial cells (HUVEC). METHODS: HUVEC were subjected to peroxidation by hydrogen peroxide. The modulation of nitric oxide (NO) release by hCG and its effects on cell viability, glutathione (GSH) levels, mitochondrial membrane potential and mitochondrial transition pore opening (MPTP) were examined by specific dyes. Endothelial and inducible NO synthase (eNOS and iNOS), Akt and extracellular -signal-regulated kinases 1/2 (ERK1/2) activation and markers of apoptosis were analyzed by Western Blot. RESULTS: In HUVEC, hCG reduced NO release by modulating eNOS and iNOS. Moreover, hCG protected HUVEC against oxidative stress by preventing GSH reduction and apoptosis, by maintaining Akt and ERK1/2 activation and by keeping mitochondrial function. CONCLUSION: The present results have for the first time shown protective effects exerted by hCG on vascular endothelial function, which would be achieved by modulation of NO release, antioxidant and antiapoptotic actions and activation of cell survival signalling. These findings could have clinical implications in the management of pregnancy-related disorders.

Osteoporosis's Menopausal Epidemiological Risk Observation (O.M.E.R.O.) study.

Osteoporosis (OP) and related fractures are well-known severe conditions affecting quality of life and life expectancy of postmenopausal women, with high economic costs in Europe. On behalf of The Italian Society of Gynecology and Obstetrics (Società Italiana di Ginecologia ed Ostetricia, SIGO), the Osteoporosis's Menopausal Epidemiological Risk Observation (O.M.E.R.O.) study, a national multicenter study on clinical risk factors of OP was organized, using FRAX® tool as a reference. Here, data from this study are presented, showing an important portion of Italian postmenopausal women affected by osteopenia/OP at high risk of fracture and the need to do prevention and/or treatment. Gynecologist can be a primary specialist in this important challenge.

In anesthetized pigs human chorionic gonadotropin increases myocardial perfusion and function through a ß-adrenergic-related pathway and nitric oxide.

Human chorionic gonadotropin (hCG) is not only responsible for numerous pregnancy-related processes, but can affect the cardiovascular system as well. So far, however, information about any direct effect elicited by hCG on cardiac function, perfusion, and the mechanisms involved has remained scarce. Therefore, the present study aimed to determine the primary in vivo effect of hCG on cardiac contractility and coronary blood flow and the involvement of autonomic nervous system and nitric oxide (NO). Moreover, in coronary endothelial cells (CEC), the intracellular pathways involved in the effects of hCG on NO release were also examined. In 25 anesthetized pigs, intracoronary 500 mU/ml hCG infusion at constant heart rate and aortic blood pressure increased coronary blood flow, maximum rate of change of left ventricular systolic pressure, segmental shortening, cardiac output, and coronary NO release (P < 0.0001). These hemodynamic responses were graded in a further five pigs. Moreover, while blockade of muscarinic cholinoceptors (n = 5) and of α-adrenoceptors (n = 5) did not abolish the observed responses, ß1-adrenoceptors blocker (n = 5) prevented the effects of hCG on cardiac function. In addition, ß2-adrenoceptors (n = 5) and NO synthase inhibition (n = 5) abolished the coronary response and the effect of hCG on NO release. In CEC, hCG induced the phosphorylation of endothelial NO synthase through cAMP/PKA signaling and ERK1/2, Akt, p38 MAPK involvement, which were activated as downstream effectors of ß2-adrenoceptor stimulation. In conclusion, in anesthetized pigs, hCG primarily increased cardiac function and perfusion through the involvement of ß-adrenoceptors and NO release. Moreover, cAMP/PKA-dependent kinases phosphorylation was found to play a role in eliciting the observed NO production in CEC.

Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice.

Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghrelin is a peptide hormone that stimulates growth hormone (GH) release and positive energy balance through binding to the receptor GHSR-1a. Only acylated ghrelin (AG), but not the unacylated form (UnAG), can bind GHSR-1a; however, UnAG and AG share several GHSR-1a-independent biological activities. Here we investigated whether UnAG and AG could protect against skeletal muscle atrophy in a GHSR-1a-independent manner. We found that both AG and UnAG inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3Kß-, mTORC2-, and p38-mediated pathways in myotubes. Upregulation of circulating UnAG in mice impaired skeletal muscle atrophy induced by either fasting or denervation without stimulating muscle hypertrophy and GHSR-1a-mediated activation of the GH/IGF-1 axis. In Ghsr-deficient mice, both AG and UnAG induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy. These results demonstrate that AG and UnAG act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner.

Vaginal hysterectomy and multimodal anaesthesia with bipolar vessel sailing (Biclamp(®) forceps) versus conventional suture technique: quality results' analysis.

PURPOSE: The medical and economic benefits of the transvaginal approach over the abdominal and laparoscopic methods are demonstrated in many studies. Vaginal hysterectomy with bipolar vessel sailing (BiClamp(®)) represents an example of mininvasive surgery and could be a valid and cost-benefit alternative in the surgical treatment of benign gynaecologic disease. BiClamp(®) may be carried out according to Clavè's technique with a good result in postoperative pain. METHODS: Prospective randomized study (Canadian Task Force classification I). We compared the vaginal hysterectomy with salpingo-oophorectomies with BiClamp(®) and multimodal anaesthesia (group A 30 patients) with vaginal hysterectomy with salpingo-oophorectomies and spinal anaesthesia (group B 30 patients). RESULTS: The median operating time was 33.5 min for group A and 54.5 min for group B (p < 0.0001). The median blood loss was 59.25 ml in group A and 81.75 ml in group B. The median hospital stay was 1.6 ± 0.58 days for group A and 2.55 ± 0.66 days for group B. Postoperative pain was statistically different between groups in the immediate postoperatory times, at 2 and at 6 h from the surgery and at 10 p.m. (p < 0.0001). Analyses of cost-effectiveness have stated advantages in terms of costs and indirect-direct benefits but also in earlier resumption of working. CONCLUSIONS: BiClamp(®) technique with multimodal anaesthesia has advantages from surgical, anaesthesiology and economic point of view. It is a minimally invasive surgery characterised by lower morbidity, quicker surgery times and reduced costs when compared to classical vaginal hysterectomy. BiClamp(®) technique represents a new border in vaginal surgery.

Diacylglycerol kinase α mediates 17-ß-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line through the G protein-coupled estrogen receptor GPR30.

Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (DGKs) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. DGK α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that DGK α activity is required for 17-ß-estradiol (E2)-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line. Impairment of DGK α activity also influences basal cell proliferation and growth in soft agar of Hec-1A, while it has no effects on basal cell motility. Moreover, we show that DGK α activity induced by E2, as well as its observed effects, are mediated by the G protein-coupled estrogen receptor GPR30 (GPER). These findings suggest that DGK α may be a potential target in endometrial cancer therapy.

Accuracy and efficacy of narrow-band imaging versus white light hysteroscopy for the diagnosis of endometrial cancer and hyperplasia: a multicenter controlled study.

OBJECTIVE: The aim of this study was to evaluate, in a multicenter study, whether the narrow-band imaging (NBI) technology may improve the diagnostic reliability of hysteroscopy in the diagnosis of endometrial cancer and hyperplasia. METHODS: A total of 801 outpatient women undergoing diagnostic hysteroscopy were enrolled. All women underwent fluid minihysteroscopy with white light (WL) and NBI exploration with endometrial eye-directed biopsy. RESULTS: NBI hysteroscopy significantly improved the sensitivity for diagnosing endometrial cancer compared with WL (93% and 81%, P < 0.05). In detecting low-risk hyperplasia, the use of NBI significantly improved the sensitivity (82% vs 56%, P < 0.005) and positive predictive value (79% and 71%, P < 0.05) compared with WL hysteroscopy. In the diagnosis of high-risk hyperplasia, NBI significantly improved the sensitivity (60% vs 20%, P < 0.005) and positive predictive value (67% and 25%, P < 0.0001), whereas no difference was seen for specificity (99% and 99%, P > 0.005), negative predictive value (99% and 99%, P > 0.05), and accuracy (99% and 98%, P > 0.05). CONCLUSIONS: NBI showed significantly higher values in sensitivity for the detection of low-risk and high-risk hyperplasia, and this could be useful for reducing the risk of missing severe pathologies at hysteroscopy, and improving the diagnosis of preneoplastic and neoplastic pathologies. NBI hysteroscopy showed a very high diagnostic accuracy for the exploration of the uterine cavity, reducing the number of biopsies performed in wrong areas, although multicenter randomized trials are required to establish the true value of this interesting technological advancement.

Laparoendoscopic single-site surgery for treatment of concomitant ovarian cystectomy and cholecystectomy.

Since the first laparoscopic appendectomy was performed by Semm in 1983, laparoscopic surgery has become the criterion standard surgical route for treatment of several pathologic conditions across disciplines. Attempts to minimize access-related injuries and complications resulted in development of laparoendoscopic single-site surgery (LESS), which, because of the decreased number of ports used, may be the next generation of minimally invasive surgery. Laparoscopic single-site surgery has been reported in nephrectomy, pyeloplasty, radical prostatectomy, cholecystectomy, and colorectal, bariatric, and gynecologic surgery. This technique may increase the benefits of traditional minimally invasive surgery such as decreased blood loss and postoperative pain, faster recovery time, fewer complications, and better cosmetic results, without increasing costs. Herein, we present a case report of single-port laparoscopic ovarian cystectomy and concomitant cholecystectomy performed with a multi-instrument access port (TriPort; Olympus America Inc., Center Valley, Pennsylvania). Single-port surgery eliminates the problem of multiple and different site placement for accessory ports, typical of these procedures when performed simultaneously at conventional laparoscopy.

Narrow-band imaging in diagnosis of endometrial cancer and hyperplasia: a new option?

STUDY OBJECTIVE: To estimate whether the use of narrow-band imaging (NBI) hysteroscopy increases concordance between visual identification and a histologic diagnosis of endometrial cancer and hyperplasia. DESIGN: Prospective study (Canadian Task Force classification: II-2). SETTING: Department of obstetrics and gynecology, University of Eastern Piedmont, Novara, Italy. PATIENTS: 209 consecutive patients with abnormal uterine bleeding. INTERVENTIONS: White-light hysteroscopy and NBI hysteroscopy followed by direct biopsy. MEASUREMENTS AND MAIN RESULTS: The sensitivity and specificity of conventional hysteroscopy in predicting a diagnosis of cancer and hyperplasia were, respectively, 84.21% (95% confidence interval [CI], 79.27-89.15) and 99.47% (95% CI, 98.49-100.0), and 64.86% (95% CI, 58.39-71.34) and 98.77% (95% CI, 97.27-100.0), and of NBI hysteroscopy were 94.74% (95% CI, 91.71-97.76) and 97.89% (95% CI, 95.95-99.84), and 78.38% (95% CI, 72.8-83.96) and 97.67% (95% CI, 96.63-99.72). The concordance of conventional and NBI hysteroscopy with the histopathologic findings (measured using the Cohen kappa) was, respectively, 88.80% (95% CI, 86.2%-96.3%) and 91.78% (95% CI, 89.6%-98.2%), a difference of 2.98% (95% CI, 0-9) in favor of NBI. CONCLUSION: Narrow-band imaging hysteroscopy can accurately predict a histologic diagnosis of endometrial cancer or hyperplasia.