Search

Introduction The RhoA/ROCK calcium-sensitizing pathway plays a role in clitoral contractility, and therefore we deemed interesting to investigate its involvement in the vagina. Objective The aim of this study was to investigate the sex steroid regulation of the vagina contractility through the RhoA/ROCK pathway, using a validated animal model. Methods Ovariectomized Sprague-Dawley rats (OVX) were treated with 17β-estradiol (E2), testosterone (T), with or without letrozole (T+L), and compared with intact animals. Contractility studies were performed on vaginal strips to test the effect of ROCK inhibitor Y-27632 and NO synthase inhibitor L-NAME. In vaginal tissues, ROCK1 immunolocalization was investigated, mRNA expression was analyzed by semi-quantitative RT-PCR, and RhoA membrane translocation was evaluated by Western blot (Wb) analysis. Finally, rat smooth muscle cells (rvSMCs) were isolated from distal vagina of intact animals and the quantification of RhoA inhibitory protein RhoGDI was performed by Wb after stimulation with NO-donor SNP, with or without the soluble guanylate cyclase inhibitor ODQ or the PKGR1 inhibitor KT5823 administration. Results The results show that ROCK1 was immunolocalized in the smooth muscle bundles and in the blood vessel wall of vagina, while a weak positivity was detected in the epithelium. Y-27632 induced a dose-dependent relaxation of noradrenaline pre-contracted vaginal strips, decreased by OVX and completely restored by E2, while T and T+L further decreased it even below OVX level increased it. Accordingly, in Wb analysis, compared to controls, OVX significantly induced RhoA activation, as reveled by its membrane translocation, with T reverting it at a level significantly lower than in controls. This effect was not exerted by E2. Abolishing the NO formation via L-NAME increased Y-27632 responsiveness in the OVX+T group; L-NAME had only a partial effect in controls whilst it did not modulate Y-27632 responsiveness in OVX. Finally, stimulation of rvSMCs with SNP significantly increased the RhoGDI protein expression, an effect counteracted by ODQ and, partially, by the protein kinase inhibitor KT5823 incubation. Conclusions In conclusion, in vagina androgen administration in OVX functionally decreases RhoA/ROCK activity by hampering RhoA membrane translocation and plays a critical role in the inhibitory mechanism of the smooth muscle distal vagina contractility. Accordingly, androgens, by inhibiting the RhoA/ROCK pathway, could positively contribute to vaginal smooth muscle relaxation, favoring the sexual intercourse. Disclosure No

Purpose Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model. Methods Subgroups of OVX Sprague–Dawley rats were treated with 17β-estradiol, testosterone, or testosterone and letrozole, and compared with a group of intact animals. Masson’s trichrome staining was performed for morphological evaluation of the distal vaginal wall, in vitro contractility studies investigated the effect of OVX and in vivo treatments on vaginal smooth muscle activity. RNA from vaginal tissue was analyzed by semi-quantitative RT-PCR. Results Immunohistochemical analysis showed that OVX induced epithelial and smooth muscle structural atrophy, testosterone and testo + letrozole increased the muscle bundles content and organization without affecting the epithelium while 17β-estradiol mediated the opposite effects. In vitro contractility studies were performed on noradrenaline pre-contracted vaginal strips from each experimental group. Acetylcholine (0.001–10 µM) stimulation induced a concentration-dependent relaxation, significantly reduced by NO-synthase inhibitor L-NAME and by guanylate cyclase inhibitor ODQ. OVX resulted in a decreased responsiveness to acetylcholine, restored by testosterone, with or without letrozole, but not by 17β-estradiol. OVX sensitivity to the NO-donor SNP was higher than in the control. Vardenafil, a PDE5 inhibitor, enhanced SNP effect in OVX + testosterone as well as in control, as supported by RNA expression analysis. Conclusions Our study demonstrates that testosterone improves the NO-mediated smooth muscle vaginal cells relaxation confirming its role in maintaining the integrity of muscular relaxant machinery.

Introduction Female sexual response is a complex phenomenon that involves multiple psychophysiological factors. Sex steroids play a fundamental role in the mechanisms of regulation of sexual arousal, modulating the sexual response and preserving the integrity and functionality of the vaginal tissue. For this reason, imbalances in the sexual environment of steroids in women favor the onset of important pathophysiological conditions such as hypoactive sexual desire disorder (HSDD) and genitourinary syndrome of menopause (GSM). Previous research has focused primarily on the effects of estrogen supplementation on vaginal physiology, but only few studies evaluated the effects of androgen administration, particularly on the vaginal smooth muscle compartment. The calcium sensitizing pathway of RhoA/ROCK may play a role in regulating vaginal contractility but, at present, the regulatory mechanisms of RhoA/ROCK signaling in the female genitourinary tract have yet to be fully elucidated. In particular, no specific research has been conducted on the effects of testosterone (T) on the contractility mechanism of smooth muscle in the vagina. Objective The aim of this study was to evaluate the sex steroid regulation on the distal vagina contractility mechanism, mediated by the RhoA/ROCK pathway, using a validated animal model of female ovariectomized rats. Methods Ovariectomized Sprague-Dawley rats (OVX) were treated with 17β-estradiol (OVX+E), testosterone (OVX+T), or testosterone and letrozole (OVX+T+L) and compared with an intact animals’ group (CTRL). In vitro contractility studies were performed on noradrenaline (NA) pre-contracted vaginal strips to investigate the effect of OVX and in vivo treatments on vaginal smooth muscle activity. The mRNA from vagina tissues isolated from each experimental group was analyzed by semi-quantitative RT-PCR, and membrane translocation of RhoA was evaluated by Western blot analysis. Results Y-27632 induced a dose-dependent relaxation on NA pre-contracted vaginal strips that was significantly decreased by OVX; T, with or without L, further decreased OVX-induced hyporesponsiveness to Y-27632, whilst it was fully restored up to control level by 17β-estradiol (E) supplementation. Accordingly, gene expression analysis indicated that OVX decreased the expression of RhoA/ROCK pathway markers, which was normalized by E. However, at variance with contractility results, androgen receptor (AR) activation upregulated, rather than downregulating, RhoA/ROCK expression. In Western blot analysis, OVX induced activation and membrane translocation of the active form of RhoA as compared to controls. Interestingly, T reverted this effect by reducing RhoA translocation to membrane to a level even significantly below the control one. This effect was not exerted by E administration. Considering that AR activation increases NO signaling (as measured by Prkg1 mRNA expression), we tested the effect of abolishing NO formation through the NO synthase inhibitor L-NAME. Pre-incubation with L-NAME substantially increased Y-27632 responsiveness in the OVX +T group and partially in the CTRL one and, but not in the OVX group. Conclusions This study confirms that in vagina estrogens increase the expression of the calcium-sensitizing pathway RhoA/ROCK, while androgen administration functionally decreases RhoA/ROCK activity, by hampering RhoA translocation to the membrane, a mechanism which is most probably driven by NO. Disclosure No

Helicobacter pylori is the most frequent cause of chronic active gastritis (CAG), namely the first step for gastric cancer development. When infection is not detected at histology, another test is advised. EndoFaster is novel device that reveal the presence of H. pylori by determining ammonium concentration in the gastric juice during endoscopy. We evaluated whether this test may improve etiological diagnosis in CAG patients. In 595 consecutive patients who underwent upper endoscopy gastric juice was analysed with EndoFaster and standard biopsies were taken. CAG with typical bacteria was detected in 102 (17.1%) patients, and CAG without H. pylori was found in 36 (6.3%) cases. EndoFaster detected the infection in 22 (61.1%) of these patients. Neither ongoing proton pump inhibitor therapy nor previous eradication therapy affect the test accuracy. By using EndoFaster, another test to search for the infection in H. pylori-negative CAG patients may be avoided in more than 60% of cases, impacting on both patients discomfort and health resources use.

Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model.Subgroups of OVX Sprague-Dawley rats were treated with 17β-estradiol, testosterone, or testosterone and letrozole, and compared with a group of intact animals. Masson's trichrome staining was performed for morphological evaluation of the distal vaginal wall, in vitro contractility studies investigated the effect of OVX and in vivo treatments on vaginal smooth muscle activity. RNA from vaginal tissue was analyzed by semi-quantitative RT-PCR.Immunohistochemical analysis showed that OVX induced epithelial and smooth muscle structural atrophy, testosterone and testo + letrozole increased the muscle bundles content and organization without affecting the epithelium while 17β-estradiol mediated the opposite effects. In vitro contractility studies were performed on noradrenaline pre-contracted vaginal strips from each experimental group. Acetylcholine (0.001-10 µM) stimulation induced a concentration-dependent relaxation, significantly reduced by NO-synthase inhibitor L-NAME and by guanylate cyclase inhibitor ODQ. OVX resulted in a decreased responsiveness to acetylcholine, restored by testosterone, with or without letrozole, but not by 17β-estradiol. OVX sensitivity to the NO-donor SNP was higher than in the control. Vardenafil, a PDE5 inhibitor, enhanced SNP effect in OVX + testosterone as well as in control, as supported by RNA expression analysis.Our study demonstrates that testosterone improves the NO-mediated smooth muscle vaginal cells relaxation confirming its role in maintaining the integrity of muscular relaxant machinery.

Pancreatic neoplasia if early detected is potentially curable. This increases the importance of screening in patients at risk. Despite having an incomplete understanding of risk factors for pancreatic cancer, some guidelines are now available helping to select and to screen high-risk individuals. Five groups of high-risk individuals have been detected: patients with a family history of pancreatic cancer, pancreatic cancer associated with inherited cancer syndrome (mutation carriers), history of pancreatitis, elderly patients with new-onset of type 2 diabetes, and patients with precancerous lesions of the pancreas. Principal modalities of imaging to detect pancreatic tumor are endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography, multidetector computed tomography, positron emission tomography, probe-based confocal laser endomicroscopy, and endoscopic cholangiopancreatography but EUS and MRI are considered the most accurate choice for pancreatic imaging screening. In particular, evidence suggests that EUS may have distinct advantages in pancreatic cancer diagnosis when compared to other modalities. EUS can provide high-resolution images of the pancreas, can accurately detect IPMNs, and can visualize characteristics that are signal of increased risk of malignancy.

Background and aims: Adequate bowel cleansing is critical to ensure quality and safety of a colonoscopy. A novel 1-L polyethylene glycol plus ascorbate (1L-PEG+ASC) regimen was previously validated against low-volume regimens but was never compared with high-volume regimens. Methods: In a phase IV study, patients undergoing colonoscopy were randomized 1:1 to receive split-dose 1L PEG+ASC or a split-dose 4-L PEG-based regimen (4L-PEG) in 5 Italian centers. Preparation was assessed with the Boston Bowel Preparation Scale (BBPS) by local endoscopists and centralized reading, both blinded to the randomization arm. The primary endpoint was noninferiority of 1L-PEG+ASC in colon cleansing. Secondary endpoints were superiority of 1L-PEG+ASC, patient compliance, segmental colon cleansing, adenoma detection rate, tolerability, and safety. Results: Three hundred eighty-eight patients (median age, 59.8 years) were randomized between January 2019 and October 2019: 195 to 1L-PEG+ASC and 193 to 4L-PEG. Noninferiority of 1L-PEG+ASC was demonstrated for cleansing in both the entire colon (BBPS≥ 6: 97.9% vs 93%; relative risk [RR], 1.03; 95% confidence interval [CI], 1.001-1.04; P superiority= .027) and in the right-sided colon segment (98.4% vs 96.0%; RR, 1.02; 95% CI, .99-1.02; P noninferiority= .013). Compliance was higher with 1L-PEG+ASC than with 4L-PEG (178/192 [92.7%] vs 154/190 patients [81.1%]; RR, 1.10; 95% CI, 1.05-1.12), whereas no difference was found regarding safety (moderate/severe side effects: 20.8% vs 25.8%; P= .253). No difference in adenoma detection rate (38.8% vs 43.0%) was found. Conclusions: One-liter PEG+ASC showed noninferiority compared with 4L-PEG in achieving adequate colon cleansing and provided a higher patient compliance. No differences in tolerability and safety were detected. (Clinical trial registration number: NCT03742232.).

Introduction The human vagina is extremely sensitive to hormonal changes occurring during the woman's lifetime, in particular the decline in estrogens that characterizes the menopause is known to induce a range of genital and sexual symptoms (dryness, burning, irritation, lack of lubrication, discomfort, pain), known as “genitourinary syndrome of menopause” (GSM). However, this reduction in estrogen levels is also accompanied by a progressive ageing-dependent decline in androgens for which the role of androgens in the development and treatment of GSM has received more attention. It is known that peripheral tissues compensate for circulating hormonal imbalances through the in-situ production of small quantities of sex hormones deriving from inactive precursors metabolized by specific cellular enzymes. This non-classical production and local activity of hormones is defined as “intracrinology”. Objective The aim of the study was to investigate whether the human vagina possesses the specific enzymatic machinery to convert weak androgen precursors, such as DHEA, into active androgens [Δ4-androstenedione (A), testosterone (T) and dihydrotestosterone (DHT)] as already described in other species. Methods In this study, a well established model of human smooth muscle cells (hSMCs), isolated from vagina tissues of women undergoing surgery for benign gynecological diseases, was used. Semi-quantitative RT-PCR was employed in order to evaluate the mRNA expression of the steroidogenic markers in hSMCs and corrispective tissue. The production of androgens was quantified in hSMCs medium by liquid chromatography tandem-mass spectrometry (LC-MS/MS). Results In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α (ERα), whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of pro-androgenic steroidogenic enzymes (HSD3β1/β2, HSD17β3/β5), along with 5α-reductase isoforms and sulfo-transferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone (T) and dihydrotestosterone (DHT) secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. Conclusions This study provides evidence for the presence of steroidogenic machinery in the human vagina, supporting, for the first time, the construct of intracrinology in this organ, emphasizing that the vagina is an androgen-dependent organ. These observations suggest the potential mechanism and resulting action of intravaginally administered DHEA, recently indicated for the treatment of GSM and open new perspectives for the treatment of this common and bothersome condition. Disclosure Work supported by industry: no.

Active restoration is considered a profitable strategy to return ecosystems to their predisturbance state, in a reasonable time frame. However, ecological restoration of marine ecosystems is still in its infancy if compared to the terrestrial context. A review of 498 studies published in the last 25 years was carried out within the MERCES H2020 EU project to understand the effects of marine restoration actions across coastal habitats at global scale. Here, an overview focused on the Mediterranean Sea was carried out to identify both contextual and methodological determinants of restoration success in the basin. Results show that restoration efforts across habitats are increasing, especially in seagrasses and saltmarshes, but never approached at ecosystem level. Targets, methods, response variables and standards are still very heterogeneous. Short project duration (one-two years), small restoration areas (< 1 ha), lack of controls and knowledge of baselines are still a limit for deriving generalities. Finally, restorations rarely consider future challenges linked to global change, thus impairing long- term success stories. Marine restoration is a promising approach to counteract habitat loss in coastal areas. However, restoration science needs more robust approaches leading to the development of best practices (e.g. protocols, monitoring of the effects, reasons for failure) to be applied at spatial and temporal scales so as to answer to present and future disturbance regimes.

Low Back Pain (LBP) is the most common spine disease and it is the most common cause of absence from work in developed countries. At lumbar level, the natural history of herniated disc is characterized by a disappearance of clinical symptoms in up to 60% with conservative treatment through simple rest for about 6 weeks and reduction of the disk heniation revealed by CT or MR scans within eight to nine months after the onset of back pain. Surgery is considered the treatment of choice for extruded, migrated and free fragment herniated disk associated to clinical symptomatology of cono-cauda syndrome, progressive foot droop and hyperalgic radiculopathy. patients with a small or contained herniated disk, without any benefit from conservative medical treatment, can be candidates for one of minimally invasive percutaneous techniques, whose outcome, though, depends on the characteristics of hernia itself and on the chosen technique. The aim of this paper is to discuss about O2-O3 treatment for symptomatic not extruded herniated disk at lumbar level, highlighting about indication inclusion exclusion criteria and our results.

The potential role of the probe-based confocal laser endomicroscopy (pCLE) has been analyzed in different pathologic conditions of the gastrointestinal tract. Here, we analyzed a case of extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) using, for the first time, the pCLE system. A 72-year old man was diagnosed with an 8 cm diameter rectal HGNEC by standard colonoscopy integrated with the pCLE system. The diagnosis of neuroendocrine carcinoma was confirmed by immunohistochemical analyses. By using the pCLE system, we well defined and resolved vascular structures and mucosal architecture. An altered mucosal pattern and vascular defects, peculiar for HGNEC, were observed at high magnification, allowing the identification of a pattern which was quite different from that observed in poorly differentiated adenocarcinomas (PDA) where tissues appear darker, very irregular, even if glandular structures can still be recognized. This underlines the usefulness of pCLE in discriminating HGNECs from PDAs. In conclusion, pCLE could represent a valid and helpful method for in vivo HGNEC diagnosis, allowing prompt and careful management of the patient.

In this contribution, we present the main results of the recent and ongoing research activities on metamaterials developed as a joint collaboration between Roma Tre University and Finmeccanica. The main goal of the applied research is focused on the development of miniaturized microwave components for radar and communication systems. The exploitation of innovative metamaterial concepts has led to the development of innovative industrial products for passive beam-forming networks of polarimetric antennas and compact radiating systems. This research has been awarded with the Finmeccanica Innovation Award in 2014 and the Finmeccanica Innovation Award for young researchers in 2015, respectively. The research activities leading to these two prestigious industrial awards are briefly summarized in this paper.

Background In patients with asthma, particularly severe asthma, poor adherence to inhaled drugs negatively affects the achievement of disease control. A better adherence rate is expected in the case of injected drugs, such as omalizumab, as they are administered only in a hospital setting. However, adherence to omalizumab has never been systematically investigated. The aim of this study was to review the omalizumab drop-out rate in randomized controlled trials (RCTs) and real-life studies. A comparative analysis was performed between published data and the Italian North East Omalizumab Network (NEONet) database. Results In RCTs the drop-out rate ranged from 7.1 to 19.4 %. Although the reasons for withdrawal were only occasionally reported, patient decision and adverse events were the most frequently reported causes. In real-life studies the drop-out rate ranged from 0 to 45.5 %. In most cases lack of efficacy was responsible for treatment discontinuation. According to NEONet data, 32 % of treated patients dropped out, with an increasing number of drop outs observed over time. Patient decision and lack of efficacy accounted for most treatment withdrawals. Conclusions Treatment adherence is particularly crucial in patients with severe asthma considering the clinical impact of the disease and the cost of non-adherence. The risk of treatment discontinuation has to be carefully considered both in the experimental and real-life settings. Increased knowledge regarding the main reasons for patient withdrawal is important to improve adherence in clinical practice.

This study assessed the impact and modification of intradiscal, intraforaminal, epidural and intramuscular swine injection of a new material, Discogel®- radiopaque gelified ethanol-recently introduced for the mini-invasive treatment of herniated disc. Discogel® is a sterile viscous solution containing ethyl alcohol, cellulose derivative product, added to a radio-opaque element, tungsten. The pig was sedated and under fluoroscopy guidance a needle was positioned within disc L1-L2 followed by intradiscal, intraforaminal, epidural and intramuscular injection of 1 ml of Discogel. As disc control level L4-L5 was considered where nothing was injected. The pig was sacrifed 48 h after injection of discogel and the spine from D10 to S1 was removed and fixed in 10% buffered formalin. The anatomical specimens were cut with an electric saw and analyzed by routine technique then stained with formalin. The specimens containing bone material were treated by DEKAL solution. The specimens were stained with hematoxylin-eosin method and then analyzed by histochemical (Masson — Van Gieson PAS and trichromic stains) and immunochemical methods. Morphostructural examination disclosed a granular material coloured black by hematoxylin-eosin method (tungsten) in paravertebral tissue both in the muscular and connective tissue. Some inflammatory elements like lymphomonocyte cells and venous stasis were found. No alteration was found where discogel was injected, and the nucleus pulposus, disc, chondromixoid and root ganglium were normal. After intradiscal, intraforaminal, epidural and intramuscular injection of Discogel® no morpho-structural changes in nuclear tissue and annulus were found. Further studies on pigs with immunohistochemical analysis after treatment will confirm the morphological alterations induced by discogel and its action.

We consider the process of hemodialysis performed by means of a hollow fiber dialyzer with a special focus on the dynamics of the light solutes (including metabolic waste products) through the porous fibers membrane. The model we illustrate here completes the one formulated in a previous paper in which solutes concentrations in the dialyzate were neglected. Exploiting the large difference between the characteristic time of the processes in the machine and the relaxation time to equilibrium in the body, we confine our study to the case of constant input data in order to emphasize the role of the solute transport mechanisms. Numerical solutions show that diffusion is dominant at the early stage of filtration.

In this study we examined mechanisms that regulate T-helper lymphocyte 1 (Th1) commitment in Helicobacter pylori -infected human gastric mucosa. The levels of gamma interferon (IFN-γ), interleukin-4 (IL-4), and IL-12 in total extracts of gastric biopsies taken from H. pylori -infected and uninfected patients were determined by an enzyme-linked immunosorbent assay. The levels of signal transducer and activator of transcription 4 (STAT4), STAT6, and T-box expressed in T cells (T-bet) in total proteins extracted from gastric biopsies were determined by Western blotting. Finally, the effect of a neutralizing IL-12 antibody on expression of Th1 transcription factors and the levels of IFN-γ in organ cultures of H. pylori -infected biopsies was examined. Increased levels of IFN-γ and IL-12 were found in gastric biopsy samples of H. pylori -infected patients compared to the levels in uninfected patients. In addition, H. pylori -infected biopsies exhibited high levels of expression of phosphorylated STAT4 and T-bet. Higher levels of IFN-γ and expression of Th1 transcription factors were associated with greater infiltration of mononuclear cells in the gastric mucosa. By contrast, production of IL-4 and expression of phosphorylated STAT6 were not associated with the intensity of mononuclear cell infiltration. In ex vivo organ cultures of H. pylori -infected biopsies, neutralization of endogenous IL-12 down-regulated the expression of phosphorylated STAT4 and T-bet and reduced IFN-γ production. Our data indicated that IL-12 contributes to the Th1 cell commitment in H. pylori -infected human gastric mucosa.

RADIOLOGIE ET IMAGERIE MEDICALE : Musculosquelettique - Neurologique - Maxillofaciale - 31-644-A-10

Ghrelin is a gastric hormone circulating in acylated (AG) and unacylated (UG) forms, and higher plasma total ghrelin (TG) and UG may be cross-sectionally associated with lower insulin resistance in metabolic syndrome patients. The potential value of ghrelin forms in predicting insulin resistance and its time-related changes in community-based population cohorts remains unknown.We measured TG, AG and calculated UG (TG-AG) in 716 individuals from the North-East-Italy MoMa study (age: 55 ± 9 years, BMI: 29 ± 5 kg/m(2), M/F:349/367) to test the hypothesis that circulating TG and UG, but not AG are negatively associated with insulin resistance (HOMA). We further hypothesized that baseline TG and UG negatively predict 5-year HOMA changes in a 350-individual subgroup.Baseline TG and UG were associated negatively with HOMA after adjusting for gender and body mass index (BMI). Baseline gender- and BMI-adjusted TG and UG were also negatively associated with HOMA at 5-year follow-up (n = 350), and changes in TG and UG were negatively associated with changes in HOMA (P 0.05) after adjustment for anthropometric and metabolic confounders. No statistically significant correlations were observed between AG and baseline or 5-year HOMA.In a North-East Italy community-based population cohort, plasma TG and UG but not AG are negatively associated with HOMA. TG and UG and their changes also independently predict 5-year HOMA changes. TG and UG are therefore novel potential modulators of insulin resistance and may contribute to predict its time-related changes in humans.

"A new family of waveguide power splitters based on the use of connected bi-omega particles is presented. The new layout consists of a H-plane T-junction, whose ports are characterised by the same crosssection. The output ports are both closed with a metallic screen and energy is allowed to pass through by means of a vertical slit drilled into each metallic screen. To make the transmission efficient, two identical particles, printed on the two faces of a dielectric slab, are placed across the slits. Depending on the design, at the resonant frequencies of the two bi-omega particles, either balanced or unbalanced power splitting is obtained between the two output ports. A proper set of numerical simulations and measurements confirm the effectiveness of the proposed design, which can be successfully used for realising compact and highly selective waveguide power splitters."

We describe two patients with meningiomas atypically appearing as long-standing forehead and vertex lumps. In both cases, CT scan and MRI identified large neoplasms arising in the frontal and parietal regions respectively with extra-cranial extension through the destroyed calvarium and intracranial development. At surgery in the first case the tumour was found adherent to the external dural layer without involvement of the internal layer thus falling into the ectopic class of meningiomas. In the second case, the dura appeared completely infiltrated by the neoplasm. Histological examination did not reveal any malignancy in either patient. Consequently, osteolysis was no of prognostic value. The role of neuroimaging is discussed, the relevant literature on extracranially protruding meningiomas is reviewed, and the clinical-surgical outcome is described.