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Background: Fetal growth restriction (FGR) is an obstetric condition that increases the risk of adverse neonatal outcomes. FGR antenatal care aims to decrease fetal morbidity and mortality through optimal fetal monitoring. However, no univocal strategies for late-onset FGR outpatient management are available, and this survey investigated gynaecologists' attitudes concerning outpatient frequency tests., Methods: We mailed a survey to 429 Italian gynaecologists. The primary purpose was the ambulatory care of late-onset FGR without doppler alterations evaluation. The queries estimated the self-reported medical practice regarding cardiotocography (CTG) and obstetric ultrasound exams before hospitalization. Statistical analysis was performed with Stata 14.1 (Stata corp., College Station, TX, USA) for symmetrically distributed continuous variables, and the mean differences were analyzed using the t-test. Where appropriate, the proportions between the groups were evaluated using Fisher's exact or χ 2 test. All P value <0.05 were considered statistically significant., Results: 128 responses (29.8%) from the 429 SCCAL members were available for the survey. 39.9% of respondents had a late FGR standardized protocol. Regarding non-severe FGR with normal fetal doppler, 70.8% suggested a fetal doppler study after one week (92/128), 13.8% (18/128) and 6.9% (9/128) proposed the exam, respectively, two and three times for a week. 0.8% (1/128) of respondents had a daily doppler exam, 7.7% (10/128) did not answer, and 3.1% (4/128) repeated the ultrasound exam to time for a week. The antenatal CTG was offered: 70.8% (92/128) of gynaecologists recommended one weekly CTG, whereas 13.8% (18/128) suggested two. 6.9% (9/128) recommended three weekly tests and 0.8% a daily test. 7.7% (10/128) of gynaecologists did not respond. At least, we investigated the gynaecologist's recommendations for outpatient EFW evaluation: 59.4% (76/128) repeated EFW after two weeks, 31.3% (40/128) after one week. 3.9% (4/128) and 3.1 (4/128) recommended EFW after three weeks and twice a week., Conclusions: Gynaecologists recommend unnecessary cardiotocography and ultrasound Doppler exams for non-severe late-onset FGR with normal doppler. However, additional studies and comprehensive surveys are needed to support a standardized protocol and assess the feto-maternal outcomes impact.

Background and Objectives : Genitourinary syndrome, previously defined as vulvovaginal atrophy, manifests with signs and symptoms deriving from estrogen diminution in the female genitourinary tract. Stable ozonides are derivatives of artemisinin found to be stable against strong basic and acidic conditions. Vitamin E is an important antioxidant diminishing the output of reactive oxygen species in the oxidation of fats and the emanation of free radicals, reducing cellular injury and aging. The primary aim of the present study was to assess the positive effects of an ozonide plus a vitamin E acetate-based compound (Ozoile) on genitourinary syndrome symptom relief after a maximum of 20 days of treatment. Materials and Methods : The inclusion criteria for patients' enrollment were women of child-bearing age or in menopause reporting genitourinary syndrome's related symptoms, such as pain, burning, a bad smell, dyspareunia, dryness, itching, bleeding, and nervousness. The exclusion criteria were Sjogren's syndrome and patients administered retinoic acid, an agent that causes mucosal dryness. Participants completed a questionnaire before and after 20 days of treatment. Results : The incidence of pain decreased from 16.7% to 11.8% ( p -value < 0.0001). In addition, the mean symptom intensity decreased from 2.10 to 0.87 ( p -value < 0.0001). Dryness was the most frequent pre-treatment symptom and decreased from 85.5% to 53.8% ( p -value < 0.0001) (mean: 2.21 vs. 0.90; p -value < 0.0001). Conclusions : Ozoile was effective in reducing most gynecologic symptoms related to genitourinary syndrome. However, further studies are needed to compare its effect with other standards of care.

Background and Objectives: Hormonal changes physiologically occurring in menopausal women may increase the risk of developing metabolic and vasomotor disturbances, which contribute to increase the risk of developing other concomitant pathologies, such as metabolic syndrome (MetS). Materials and Methods: Retrospective data from 200 menopausal women with MetS and vasomotor symptoms taking one sachet per day of the dietary supplement INOFOLIC ® NRT (Farmares srl, Rome, Italy) were collected. Each sachet consisted of myo-Inositol (2000 mg), cocoa polyphenols (30 mg), and soy isoflavones (80 mg, of which 50 mg is genistin). Patients recorded their symptoms through a medical questionnaire at the beginning of the administration (T0) and after 6 months (T1). Results: We observed an improvement in both the frequency and the severity of hot flushes: increased percentage of 2-3 hot flushes (28 at T0 vs. 65% at T1, p value < 0.001) and decreased percentage of 4-9 hot flushes (54% at T0 vs. 18% at T1, p value < 0.001). Moreover, symptoms of depression improved after supplementation (87% at T0 vs. 56% at T1 of patients reported moderate depression symptoms, p value < 0.001). Regarding metabolic profile, women improved body mass index and waist circumference with a reduction in the percentage of overweight and obesity women (88% at T0 vs. 51% at T1, p value = 0.01; 14% at T0 vs. 9% at T1, p value = 0.04). In addition, the number of women suffering from non-insulin dependent diabetes reduced (26% at T0 vs. 16% at T1, p value = 0.04). Conclusions: These data corroborate previously observed beneficial effects of the oral administration of myo-Inositol, cocoa polyphenols, and soy isoflavones against menopausal symptoms in the study population. Considering the promising results of the present study, further prospective controlled clinical trials are needed to deeply understand and support the efficacy of these natural compounds for the management of menopausal symptoms.

Vertical land movements can cause regional relative sea-level changes to differ substantially from climate-driven absolute sea-level changes. Whereas absolute sea level has been accurately monitored by satellite altimetry since 1992, there are limited observations of vertical land motion. Vertical land motion is generally modelled as a linear process, despite some evidence of nonlinear motion associated with tectonic activity, changes in surface loading or groundwater extraction. As a result, the temporal evolution of vertical land motion, and its contribution to projected sea-level rise and its uncertainty, remains unresolved. Here we generate a probabilistic vertical land motion reconstruction from 1995 to 2020 to determine the impact of regional-scale and nonlinear vertical land motion on relative sea-level projections up to 2150. We show that regional variations in projected coastal sea-level changes are equally influenced by vertical land motion and climate-driven processes, with vertical land motion driving relative sea-level changes of up to 50 cm by 2150. Accounting for nonlinear vertical land motion increases the uncertainty in projections by up to 1 m on a regional scale. Our results highlight the uncertainty in future coastal impacts and demonstrate the importance of including nonlinear vertical land motions in sea-level change projections., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Background and Objectives : Signs and symptoms of vulvovaginitis, especially when recurrent, have a significant impact on a woman's quality of life. The aim of this study was to survey gynecologists about their habits regarding the treatments of the pathology and to evaluate the efficacy of a novel vaginal hydrogel composed of wheat extracts and polyhexanide aimed at reducing vulvovaginitis symptomatology. Materials and Methods : A cross-sectional analysis of a national survey using 155 Italian gynecologists and a prospective, open-label, observational study were carried out in 75 outpatient clinics across Italy. Pre- and postmenopausal women with suspicion of vulvovaginitis due to at least four of the following symptoms (leucoxanthorrhea, bad odor from genitalia, vulvovaginal dryness, petechiae, burning, and pruritus) while waiting for microbiological swab analysis were included and treated with one hydrogel application every 3 days for 1 week. Primary endpoint was the complete resolution of symptomatology. Results : The pre-study survey reported that, for most clinicians, local or oral treatment (65.7% and 82.8%, respectively) with antibiotics or antifungals is used very often. Therefore, we proceeded to carry out an observational study. Overall, 615 (362 of fertile age and 253 in postmenopause) women were included in this study. At the 28th follow-up examination, complete resolution of symptomatology was achieved in 578/615 (94.1%; p < 0.001) within 12.72 ± 6.55 and 13.22 ± 6.33 days for those of fertile age and in postmenopause, respectively ( p = 0.342). All of the evaluated symptoms were significantly reduced after treatment ( p = 0.001) without differences according to the patient's menopausal status. A slightly significant reduction in Gardnerella Vaginalis ( p = 0.040) and Candida Albicans ( p = 0.049) was found after treatment. No patient reported side effects, adverse reactions, or discontinued therapy. Conclusions : This pilot study showed that a hydrogel based on Rigenase ® (wheat extract) and polyhexanide could be a promising treatment for the relief of vulvovaginitis symptoms. However, these results are limited by the absence of a control group. Additional comparative and randomized controlled trials between the hydrogel and other non-antibiotic devices as well as local antibiotic therapy should be performed to increase the validity of the findings.

Coastal studies of wave climate and evaluations of wave energy resources are mainly regional and based on the use of computationally very expensive models or a network of in-situ data. Considering the significant wave height, satellite radar altimetry provides an established global and relatively long-term source, whose coastal data are nevertheless typically flagged as unreliable within 30 km of the coast. This study exploits the reprocessing of the radar altimetry signals with a dedicated fitting algorithm to retrieve several years of significant wave height records in the coastal zone. We show significant variations in annual cycle amplitudes and mean state in the last 30 km from the coastline compared to offshore, in areas that were up to now not observable with standard radar altimetry. Consequently, a decrease in the average wave energy flux is observed. Globally, we found that the mean significant wave height at 3 km off the coast is on average 22% smaller than offshore, the amplitude of the annual cycle is reduced on average by 14% and the mean energy flux loses 38% of its offshore value.

Regulatory T (T reg ) cells are a barrier for tumor immunity and a target for immunotherapy. Using single-cell transcriptomics, we found that CD4 + T cells infiltrating primary and metastatic colorectal cancer and non-small-cell lung cancer are highly enriched for two subsets of comparable size and suppressor function comprising forkhead box protein P3 + T reg and eomesodermin homolog (EOMES) + type 1 regulatory T (Tr1)-like cells also expressing granzyme K and chitinase-3-like protein 2. EOMES + Tr1-like cells, but not T reg cells, were clonally related to effector T cells and were clonally expanded in primary and metastatic tumors, which is consistent with their proliferation and differentiation in situ. Using chitinase-3-like protein 2 as a subset signature, we found that the EOMES + Tr1-like subset correlates with disease progression but is also associated with response to programmed cell death protein 1-targeted immunotherapy. Collectively, these findings highlight the heterogeneity of T reg cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy.

Aim of the Study: To evaluate the efficacy of a nutraceutical compound containing Uticlin® (D-mannose, cranberry, bearberry, Olea europaea ), inulin, Orthosiphon and Lactobacillus acidophilus , in preventing recurrent urinary tract infections (UTIs) in menopausal women., Material and Methods: This was a prospective cohort study of menopausal women recruited with a history of recurrent UTIs in the previous twelve months and who intended to treat their bladder problem without the use of antibiotics and/or anti-inflammatories. Women were proposed the use of an oral nutraceutical compound. The drug was taken for ten days, every month. Women were assigned to two parallel cohorts: patients using (group 1) or not using (group 2) this nutraceutical compound. The primary objective of the study was to evaluate the number of women with less than two infective episodes in the 6-month follow-up and less than three episodes in the 12-month follow-up. The secondary endpoints were to evaluate the reduction of related symptoms at 12-month follow-up, according to the Visual Analog Scale (VAS)., Results: At 6 months of therapy, the reduction in the number of patients with ≥ 2 UTIs was statistically significant ( p < 0.05) compared to baseline only in group 1. At 12 months, the number of patients who were disease-free was significantly higher ( p < 0.05) in group 1 compared to group 2. Moreover, the improvement of related symptoms was statistically significant ( p < 0.05) in group 1, as shown by the reduction in the VAS scale value., Conclusions: In menopausal women, the combination of D-mannose, inulin, cranberry, bearberry, Olea europaea, Orthosiphon and Lactobacillus acidophilus SGL 11 per os represents a useful therapy for recurrent UTIs in women wanting a natural approach., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Termedia.)

Fluorescence in situ hybridization (FISH) is a powerful single-cell technique that harnesses nucleic acid base pairing to detect the abundance and positioning of cellular RNA and DNA molecules in fixed samples. Recent technology development has paved the way to the construction of FISH probes entirely from synthetic oligonucleotides (oligos), allowing the optimization of thermodynamic properties together with the opportunity to design probes against any sequenced genome. However, comparatively little progress has been made in the development of computational tools to facilitate the oligos design, and even less has been done to extend their accessibility. OligoMiner is an open-source and modular pipeline written in Python that introduces a novel method of assessing probe specificity that employs supervised machine learning to predict probe binding specificity from genome-scale sequence alignment information. However, its use is restricted to only those people who are confident with command line interfaces because it lacks a Graphical User Interface (GUI), potentially cutting out many researchers from this technology. Here, we present OligoMinerApp (http://oligominerapp.org), a web-based application that aims to extend the OligoMiner framework through the implementation of a smart and easy-to-use GUI and the introduction of new functionalities specially designed to make effective probe mining available to everyone., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Urinary tract infections (UTIs) are among the most common bacterial infection diagnosed in women. The standard therapy is represented by short course of anti-microbial treatment to eradicate causative pathogens. However, due to antibiotic treatment, normal microbiota of the gastrointestinal tract is at risk of depletion and prolonged use of antibiotics can lead to the development of resistant strains. The aim of this pilot study was to assess the efficacy of Acidif plus®, a novel preparation containing L-Methionine, Boswellia serrata and Hibiscus sabdariffa, in the treatment of UTIs in women, in comparison with standard antibiotic treatment with fosfomycin., Methods: We performed a pilot clinical study with 88 patients with uncomplicated UTIs treated in ambulatory care clinics. The subjects recruited in the study were divided into two groups: the treatment group included 57 patients with both symptomatic and asymptomatic uncomplicated, bacteriuria-positive UTIs, who were treated by oral administration of Acidif plus® two tablets per day (1 tablet in the morning and 1 tablet in the evening) for 7 days. The control group included 31 patients with both symptomatic and asymptomatic bacteriuria-positive uncomplicated UTIs, treated with fosfomycin for two consecutive days. Clinical improvement of symptoms and urine bacteriuria were evaluated as treatment outcomes., Results: More than 50% of Acidif plus® treated patients were free of symptoms of UTIs at the end of the treatment regime. In addition, Acidif plus® treatment was effective in eliminating the bacterial infection in the post-treatment urine cultures in more than 85% of the patients., Conclusions: In this study Acidif plus® treatment in patients with uncomplicated UTIs was found to be non-inferior to the standard antibiotic therapy. In acute setting, Acidif plus® was shown to be even more effective in alleviating the symptoms than fosfomycin and in eliminating bacteria in urine cultures. It is therefore possible to propose Acidif plus® as a potential alternative option to reduce the problem of multi-drug resistance in urinary infections.

Objective: Adjuvants or alternatives to antibiotics in urinary tract infections (UTIs) during pregnancy seem advisable because of possible fetal stress. The present study assessed the effectiveness of a food supplement containing L-methionine and Hibiscus sabdariffa L. and Boswellia serrata Roxb. extracts as a treatment for symptomatic UTIs in pregnancy., Design: Pregnant patients with symptomatic cystitis were screened for UTIs in three different clinical centers. Those unwilling to take antibiotics were offered two alternative treatments: (A) a 1-week treatment with the food supplement or (B) a week in which they were advised to increase their fluid consumption to more than 1.5 L daily. After 1 week, group B patients who still had positive urine cultures (UCs) or had no UC performed took the food supplement for an additional week. UCs were performed on all patients at the first visit (w0) and on most of them at 7 days (w1). Patients who were still positive at w1 or had no UC performed at w1 had UC performed 14 days (w2) thereafter., Results: Of 264 pregnant women enrolled, 216 joined group A, while 48 joined group B. At w1, 70.0% of group A patients and 43.2% of those in group B had negative UCs (p = 0.003). The reduction of bacterial load was 42.2% ± 8.0% and 4.5% ± 9.2%, respectively (p < 0.0001). At w1, symptoms disappeared in 135 patients (62.5%) in group A and 22 patients (45.8%) in group B (p = 0.03). At w2, 30 of 32 group B patients who switched to taking the supplement for the second week had negative UCs, including 20 who had been positive at w1. At w2, all group A patients had negative UCs. No side effects were reported., Conclusions: The food supplement provided effective treatment and might be an adjuvant or alternative to antibiotic therapy of symptomatic UTI in pregnancy.

This paper is the second of a series dealing with clusters formation mechanism. In part 1, water clusters with the addition of an electrophilic molecule such as ethanol were studied by Time Of Flight Mass Spectrometry (TOFMS). Mass distributions of molecular clusters of ethanol, water and ethanol-water mixed clusters, were obtained by means of two different ionization methods: Electron Ionization (EI) and picosecond laser Photo-Ionization (PI) at a wavelength of 355 nm. In part 2, the same experimental approach was employed to obtain mass spectra of clusters generated by acetone-water binary mixtures with a different composition. Strong dependence of the mass spectra of clusters with EI and PI on the acetone-water mixing ratio was observed. It was shown that the spectral pattern changes gradually and water-rich cluster signals become fainter while acetone-rich cluster signals become more intensive with increasing acetone concentrations from 0.3% to 40%. Owing to the hydrogen bond acceptor character of acetone, its self-association is discouraged with respect to ethanol. The autocorrelation function (AF) was used to analyze the variation of the water clusters composition with the increase of the acetone concentration in terms of fundamental periodicities. However, although acetone and ethanol present a very different hydrogen-bonding ability, similarly to ethanol-water system, in acetone-water system the formation of water-rich clusters and subsequent metastable fragmentation are the dominant process that determine the clusters distribution, irrespective of the ionization process, while the ionization process significantly affects the acetone-rich clusters distribution. Graphical Abstract ᅟ.

Rationale: Time-of-Flight (TOF) Mass Spectrometry is a powerful analytical technique, provided that an accurate calibration by standard molecules in the same m/z range of the analytes is performed. Calibration in a very large m/z range is a difficult task, particularly in studies focusing on the detection of high molecular weight clusters of different molecules or high molecular weight species., Methods: External calibration is the most common procedure used for TOF mass spectrometric analysis in the gas phase and, generally, the only available standards are made up of mixtures of noble gases, covering a small mass range for calibration, up to m/z 136 (higher mass isotope of xenon). In this work, an accurate calibration of a Molecular Beam Time-of Flight Mass Spectrometer (MB-TOFMS) is presented, based on the use of water clusters up to m/z 3000., Results: The advantages of calibrating a MB-TOFMS with water clusters for the detection of analytes with masses above those of the traditional calibrants such as noble gases were quantitatively shown by statistical calculations. A comparison of the water cluster and noble gases calibration procedures in attributing the masses to a test mixture extending up to m/z 800 is also reported. In the case of the analysis of combustion products, another important feature of water cluster calibration was shown, that is the possibility of using them as "internal standard" directly formed from the combustion water, under suitable experimental conditions., Conclusions: The water clusters calibration of a MB-TOFMS gives rise to a ten-fold reduction in error compared to the traditional calibration with noble gases. The consequent improvement in mass accuracy in the calibration of a MB-TOFMS has important implications in various fields where detection of high molecular mass species is required. In combustion products analysis, it is also possible to obtain a new calibration spectrum before the acquisition of each spectrum, only modifying some operative conditions. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

A natural pH gradient caused by marine CO2 seeps off Vulcano Island (Italy) was used to assess the effects of ocean acidification on coccolithophores, which are abundant planktonic unicellular calcifiers. Such seeps are used as natural laboratories to study the effects of ocean acidification on marine ecosystems, since they cause long-term changes in seawater carbonate chemistry and pH, exposing the organisms to elevated CO2 concentrations and therefore mimicking future scenarios. Previous work at CO2 seeps has focused exclusively on benthic organisms. Here we show progressive depletion of 27 coccolithophore species, in terms of cell concentrations and diversity, along a calcite saturation gradient from Ωcalcite 6.4 to <1. Water collected close to the main CO2 seeps had the highest concentrations of malformed Emiliania huxleyi. These observations add to a growing body of evidence that ocean acidification may benefit some algae but will likely cause marine biodiversity loss, especially by impacting calcifying species, which are affected as carbonate saturation falls., (© 2014 Marine Biological Laboratory.)

Water clusters are multimers of water molecules held together by hydrogen bonds. In the present work, multiphoton ionization in the UV range coupled with time of flight mass spectrometry has been applied to water clusters with up to 160 molecules in order to obtain information on the electronic states of clusters of different sizes up to dimensions that can approximate the bulk phase. The dependence of ion intensities of water clusters and their metastable fragments produced by laser ionization at 355 nm on laser power density indicates a (3+1)-photon resonance-enhanced multiphoton ionization process. It also explains the large increase of ionization efficiency at 355 nm compared to that at 266 nm. Indeed, it was found, by applying both nanosecond and picosecond laser ionization with the two different UV wavelengths, that no water cluster sequences after n = 9 could be observed at 266 nm, whereas water clusters up to m/z 2000 Th in reflectron mode and m/z 3000 Th in linear mode were detected at 355 nm. The agreement between our findings on clusters of water, especially true in the range with n > 10, and reported data for liquid water supports the hypothesis that clusters above a critical dimension can approximate the liquid phase. It should thus be possible to study clusters just above 10 water molecules, for getting information on the bulk phase structure.

Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P<0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P<0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future.

Aim: The aim of the study was to investigate if VEGF levels reflect the severity of endometrial cancer and the clinic relationship between microvasal density (MVD) and concentration of VEGF in tumor., Methods: The study was conducted on 22 patients affected by endometrial cancer who were submitted to total abdominal radical hysterectomy plus bilateral salpingo-ophorectomy. VEGF (pg/mL) and MVD values were measured on histologic specimens of endometrial cancer obtained during the surgical treatment. The means and standard deviations of estimated values were calculated and a statistical comparison was effected by student t test for not coupled data. Pearson correlation test was used to analyze the eventual correlation among VEGF and MVD values in overall patients., Results: We have documented that VEGF expression and MVD change according to FIGO stage, lympho-vascular infiltration and lymph node involvement. Pearson correlation test shows a good linear positive correlation in overall patients between VEGF and MVD values., Conclusions: Results obtained show a possible use of VEGF as prognostic factor in endometrial cancer. Confirmation of these data may permit both to identify high-risk patients, who must be treated with a more aggressive treatment, and to use an angiogenic therapy in endometrial cancer.

The term female adnexal tumor of probable Wolffian origin "FATWO" designs this tumor wich arises by the rare persisting remnants of the mesonephric duct (Wolffian duct). About 40 cases have been reported in literature. Few cases of recurrence have been reported, FATWO usually shows no signs of hormonal activity. We report a case of the youngest patient affected by FATWO in October 2002. At laparotomy the left adnexa were deformed by a well-capsulated mass, totally removed and sent to the pathologist with a specimen of peritoneal fluid and of the omentum. The histological examination showed a prevalent tubular structure with focal retiform area, without intraluminal mucines. Immunohistochemical findings of the case reported are similar to those described by other authors, except for inhibin which has not been detected by us. The cytofluorimetry showed the low presence of aneuploid cells, with a very low prolifing component (< 1%).

Introduction: Abdominal scar recurrence of endometrial carcinoma after abdominal total hysterectomy is very rare. We report a case of a 65-year-old woman who had two recurrences in the abdominal incisional scar after total hysterectomy., Case Report: A 65-year-old woman underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy because of well-differentiated endometrial adenocarcinoma (Stage IIB). Thus, the patient was treated by external beam radiotherapy. She developed two recurrences in the abdominal incisional scar two and three years after total hysterectomy, respectively. Surgery plus chemotherapy and surgery plus hormonal therapy were used for treatment of the first and second scar recurrence, respectively., Conclusions: It is a very intriguing and controversial biologic question how neoplastic cells can implant and grow in an abdominal scar without other concomitant metastases. We report a review of the literature and the possible mechanism of recurrences in laparotomy wounds.

Purpose: To assess CA-125 in defining tumor response in patients treated with paclitaxel., Patients and Methods: We analyzed 150 women treated for epithelial ovarian carcinoma with platinum or paclitaxel. We compared the patients treated with two agents, using a precise definition of CA-125 response, determined by 50% and 75% reductions, like other authors have published., Results: CA-125 criteria gave response rates very similar to the standard response rates, both for patients treated with platinum (75% vs 63%) and also for those treated with paclitaxel (40% vs 39%). Rates of false-positive prediction of response by CA-125 were also similar for patients treated with these two agents., Conclusion: Precise 50% or 75% CA-125 response criteria are as sensitive as standard criteria for assessing activity of therapy for the ovarian cancers treated with platinum or paclitaxel. We propose that they may be useful in defining response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer.

Objective: This study was conducted to examine the influence of insulin resistance on weight change in postmenopausal women of various ethnic groups., Subjects: Data were obtained from 3389 women (60% White, 20% Black, 12% Hispanic, and 8% Asian/Pacific Islander), ages 50-79, enrolled in either the Women's Health Initiative Clinical trial or Observational Study, whose blood samples were selected randomly from the full cohort of 161 809 women for analyses., Measurements: Glucose, insulin, and lipids were measured on fasting serum samples drawn at baseline and after 3 y of follow-up. Weight, height, waist circumference, and blood pressure were measured. Physical activity and energy intake were assessed via questionnaire. Insulin resistance was estimated using the HOMA (homeostasis model) calculation., Results: Average age was 62 y, average BMI (body mass index) was 27.4 kg/m2, and average weight change was a gain of 0.4 kg in 3 y. In a multivariate analysis, insulin resistance and insulin concentrations were independent predictors of increases in weight in White women (P=0.002 and 0.004, respectively) and in the combined group (P=0.027 and 0.039). For the whole group, after adjustment for other covariates, those in the highest quartile of insulin resistance gained 0.4 kg in 3 y, whereas those in the lowest quartile lost 0.06 kg. Similar trends were found for insulin resistance and weight gain in Hispanic and Asian/Pacific Islander women, but they did not reach statistical significance. In Black women, no relation was seen between either insulin or insulin resistance and weight change. A significant interaction between obesity and insulin resistance was observed (P=0.002 for White women and 0.032 for the whole group), so that there is weight gain with increasing insulin resistance in the leaner women, but weight loss with increasing insulin resistance in the most obese., Conclusion: Insulin resistance appears to be a predictor of weight gain in postmenopausal women, except for the most obese women. The effect is more pronounced in women who have a lower BMI, and the effect was not seen in the Black women who as a group had a higher BMI.

CDB-2914 (17 alpha-acetoxy-11 beta-[4-N,N-dimethylaminophenyl]-19-norpregna-4,9-diene-3,20-dione) is a 19-norprogesterone derivative that acts as an antagonist in progesterone-responsive tissues. It binds to progesterone receptors A and B with high affinity. After oral dosing in humans, CDB-2914 serum levels peak at 60-90 min. CDB-2914 binds to serum proteins and is cleared slowly. Doses of 1, 10 and 50 mg exhibit proportional increases in peak serum levels, but serum levels from higher doses, 100 and 200 mg, are not dose-dependent, suggesting saturation of carrier sites. The biological effects of CDB-2914 vary according to time of the menstrual cycle that the drug is given. In the mid-follicular phase, CDB-2914 (50 mg) inhibits follicular development and delays ovulation and menses. At 100 mg, in some cases the original follicle ceases development and a new follicle is recruited. Endometrial maturation is delayed at all doses tested (10, 50, 100 mg). Given at mid-luteal phase, there was a dose-dependent effect on menses, with higher doses (100-200 mg) resulting in earlier menses. On average, CDB-2914 tends to lengthen the menstrual cycle by approximately 1-2 days although the amount of delay varies with timing in the menstrual cycle and dose.

Background: The aim of this study is to define the role of the intestinal removal for the therapy of ovarian cancer in advanced stadium., Methods: We have examined 247 females with epithelial ovarian cancer in advanced stadium, that had intestinal removal., Results: The survival in the females that had a very good intestinal removal is greatest than in the females that hadn't a very good intestinal removal.

Background: The aim of this study is to evaluate the efficacy of cytoriductive surgical in females with ovarian carcinoma in advanced stadium, and to define the role of this surgical for the survival of females with hepatic metastases., Methods: This is a retrospective study. 164 females with ovarian cancer in IV stadium was examined. 64 females had hepatic metastasis. All patients had cytoriductive surgical., Results: The survival in the patients without hepatic metastasis was 38 months if the cytoreduction was very good; it was 18.3 months if there is residual disease. The survival in the patients with hepatic metastasis was 50.1 months if the cytoreduction was very good; it was 27 months if there is residual disease., Conclusions: A very good surgical is very important for the survival of patients with ovarian cancer in advanced stadium. This is true also in the patients with hepatic metastases.

The aspecific and exiguous symptoms and the lacking information are among the reasons of the diffusion of the vulvo-vaginal papillomatosis. We carried out the present study between 1995 and 1999 in the outpatient clinic of cervico-vaginal pathology of the Second University of Naples. 680 patients (aged between 18 and 56 years) underwent vulvoscopic and colposcopic examination. The did not show any relevant symptoms specific for HPV infection. Among the viral strains, HPV-16 and HPV 18 are able to induce a cervical cancer. To eliminate the pathology the primary prevention is necessary: it consist of both an adequate information about the micro-condilomatosis, the role of the activator agent, the modality of the infection, and the annual screening examinations such as pap-test and colposcopy. As first line treatment during secondary prevention, we utilize Roferon A, and perform diathermocoagulation according with the local diffusion and the degree of the disease (mild, moderate, severe). At the end of the therapy with Roferon A we observed that the infective focus was eliminated in about 60% of the cases and, only for moderate and severe micro-condilomatosis a diathermocoagulation was necessary.

Objective: The purpose of our studies has been that to individualize the in partnership factors of risk to infection Herpes Simplex Virus-Type 2 in pregnant women and to appraise the role of the job in such context., Methods: A champion of 79 pregnant women with infection from HSV-2 has responded to a questionnaire regarding the appearance of the infection, her own job and the degree of stress, if they used services hygienic public., Results: In this champion of pregnant women 63% they are workers. Of these the 85% they introduced signs of a reinfection. For the housewives in 67% there was a reinfection. 84% of the housewives it uses services hygienic privacies. The infection from HSV has appeared in 28.5% of the been born by women with first infection from HSV genitalis, and in 12.5% of the been born by women with reinfection from HSV., Conclusions: The women that work are mostly to risk of reinfection, they have more evident troubles. This is consequence of a style of life that contemplates a state of superior stress and a great tiredness from the same and of the appearance of vulvo-vaginal infections sustained by microorganisms transmitted through the hygienic services.

Objective: The aim of this study was to compare the time length until the human chorionic gonadotropin titer became negative after medical or surgical treatment of ectopic pregnancy., Experimental Design: Prospective, randomized study. PARTECIPANTS AND INTERVENTIONS: We compared time to resolution in 30 cases of tubal pregnancies successfully treated, 15 underwent laparoscopic linear salpingostomy (group 1) and 15 medical treatment with single-ose methotrexate (group 2). The patients of both groups had no meaningful differences of age, gestational age and human chorionic gonadotropin mean values., Measures: During the follow-up human chorionic gonadotropin serum values were obtained every two days until the titer was negative., Results: The time to resolution was 33.6 +/- 6.6 days in group 1, 31.5 +/- 7.8 in group 2 with no statistically meaningful differences., Conclusion: The data, comparable with results obtained by laparoscopic treatment, suggest that human chorionic gonadotropin value becomes negative independently of type of treatment and residual trophoblast.

Objective: To evaluate the impact of endometriosis on bone metabolism., Materials and Methods: We compared bone mineral density and biochemical markers (plasma osteocalcin, bone alkaline phosphatase, fasting urinary hydroxyproline, urinary excretion of cross-linked N-telopeptide of type I collagen) of bone turnover in forty-nine perimenopausal women undergoing laparotomy because of benign gynecologic pathology: in twenty-four of them (group A) endometriosis was diagnosed, the remaining twenty-five represented the control group (group B). Statistical analysis was performed by means of Student "t"-test; significance was set at p < 0.05., Results: Bone density of the lumbar spine (0.898 +/- 0.325 vs 0.940 +/- 0.350) and bone markers failed to show statistically significant differences between the two groups. No significant correlation was observed between any bone density measurement and severity of endometriosis., Conclusion: Endometriosis does not seem to induce even in advanced stages, a reduction of bone density.

Objective: To evaluate the relationship between hormone replacement therapy and glucose metabolism, and the possible role played by the administration route., Design: Prospective randomized study., Materials and Methods: Eighty-four patients in either surgical or spontaneous menopause were randomly allocated into four groups: 15 patients in surgical menopause were treated with estrogens alone administered transdermically (17 beta-estradiol, 50 micrograms/day); 15 patients in surgical menopause were treated with oral conjugated equine estrogens (0.625 mg/day); 18 patients in spontaneous menopause were treated with transdermic estrogens plus oral progestagen (17 beta-estradiol 50 micrograms/day, acetate medroxyprogestogen 10 mg/day for 12 days per month); 16 patients in spontaneous menopause were treated with oral conjugated equine estrogens (0.625 mg/day) plus oral progestagen (10 mg/day for 12 days per month). Twenty patients not given any medication represented the control group. Before starting the trial and after six months of therapy, glucose and insulin levels before and after an oral glucose loading test were evaluated. Data analysis was performed by means of Student's "t"-test, ANOVA was used to compare mean levels between the groups. Significance was set at p < 0.005., Results: Dosages made after 6 months of therapy showed comparable basal glucose levels in all the studied group, while basal insuline levels in patients taking estrogen alone were lower (76.88 +/- 23.66 vs 95.91 +/- 24.57 in group 1, 80 +/- 13.34 vs 96.91 +/- 18.97 in group 2) than pretreatment values. No significant difference in glucose levels was found after glucose load in the four groups. CONCLUSION. Women treated with estrogen alone have a tendency to a lower insulin response, which could indicate a greater insulin sensitivity. This effect seems to be more evident in transdermic administration than with oral administration. The addition of progestagen seems to wane the increase in insulin sensitivity induced by estrogens.

Objective: To evaluate the hospital care rendered to hyperglycemic individuals who did not have a diagnosis of diabetes before admission., Research Design and Methods: A total of 1,034 consecutively hospitalized adult patients at a 750-bed inner-city teaching hospital were evaluated. Patients with one or more plasma glucose values > 200 mg/dl were identified by the laboratory data system on a daily basis. Patients without a diagnosis of diabetes at the time of admission were evaluated to determine if and how physicians addressed the hyperglycemia, whether a new diagnosis of diabetes was made during admission, and whether follow-up was planned to address the hyperglycemia., Results: After excluding patients who were admitted for a primary diagnosis of diabetes, 37.5% of all hyperglycemic medical patients and 33% of hyperglycemic surgical patients were without a diagnosis of diabetes at the time of admission. These patients had a mean peak glucose of 299 mg/dl, and 66% had two or more elevated values during their hospitalization. Fifty-four percent received insulin therapy, and 59% received bedside glucose monitoring, yet 66% of daily patient progress notes failed to comment on the presence of hyperglycemia or diabetes. Diabetes was documented in only three patients (7.3%) as a possible diagnosis in the daily progress notes., Conclusions: Despite marked hyperglycemia, most medical records made no reference to the possibility of unrecognized diabetes. Given the average delay of a decade between the onset and diagnosis of type 2 diabetes, further evaluation of hyperglycemic hospitalized patients may present an important opportunity for earlier detection and the initiation of therapy.

The sensory nerves, containing substance P and calcitonin gene-related peptide, and noradrenaline-containing sympathetic nerves of the rat uterus were analyzed following long-term sympathectomy with guanethidine in prepubertal (four weeks), young adult (eight weeks) and fully adult animals (18 weeks). Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) long-term guanethidine treatment completely abolished the noradrenergic innervation of the uterine horn and parametrial tissue and markedly reduced the tissue levels of noradrenaline in both regions at the three ages analysed; (2) in the uterine horn guanethidine treatment had no effect on the tissue levels of either calcitonin gene-related peptide or substance P or on the density of calcitonin gene-related peptide-containing nerves, at any of the three ages studied; (3) in the parametrial tissue increased levels of calcitonin gene-related peptide were observed at 8 and 18 weeks of age, together with a significant increase in the density of calcitonin gene-related peptide-containing nerves. Substance P levels showed a transient increase in this tissue at eight weeks. In conclusion, long-term sympathectomy with guanethidine resulted in an increase in calcitonin gene-related peptide and substance P in sensory nerves in the parametrial tissue, but not in the uterine horn. The changes in the parametrial tissue only occurred after puberty. It is suggested that sensory nerves in the uterine horn may be less responsive to sympathetic denervation since loss of sympathetic nerves occurs as part of a normal physiological process during pregnancy in this region.

The plasticity of the sympathetic and sensory innervation of the rat uterus was examined, before and after puberty, in controls and in animals where primary sensory nerves had been destroyed by neonatal capsaicin treatment. Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) Puberty was associated with a marked increase in the weight of the uterine horn, uterine cervix and parametrial tissue. This was unaffected by capsaicin treatment. (2) The sympathetic innervation of the uterine horn and parametrial tissue was reduced following puberty as revealed by a decrease in the density of noradrenaline-containing nerves and a marked decrease in the tissue concentration of noradrenaline. Sympathetic nerves supplying the uterine cervix and the blood vessels of the uterus appeared to be unaffected by puberty. (3) In contrast, the sensory supply of the uterus by substance P and calcitonin gene-related peptide-containing nerves increased in parallel with uterine growth during puberty resulting in no change in nerve density and only a slight reduction in peptide concentration. (4) Neonatal capsaicin treatment caused a long-lasting depletion of substance P- and calcitonin gene-related peptide-containing nerves. In the uterine horn and parametrial tissue, capsaicin-resistant calcitonin gene-related peptide, but not substance P, still increased with tissue weight during puberty, indeed, in the uterine horn, the relative increase was greater than in controls. (5) Sensory denervation resulted in an increase in the non-vascular sympathetic supply of the uterus, although there was a regional variation in the time course of the response. Perivascular sympathetic nerves were unaffected by capsaicin treatment. The pattern of change in non-vascular noradrenaline-containing nerves associated with puberty was similar in nature to controls. Thus, there is considerable plasticity in the innervation of the uterus both during puberty and following sensory denervation. A complex pattern of change occurs with differential responses in vascular and nonvascular nerves and in different regions of the uterus. Such differences may be due in part to the different origins of individual nerve populations and/or to their relative sensitivities to sex hormones.