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Background: There has recently been growing interest in the roles of inflammation in contributing to the development of anxiety in people with immune-mediated inflammatory diseases (IMID). Patient-reported outcome measures can facilitate the assessment of physical and psychological functioning. The National Institutes of Health (NIH)'s Patient-Reported Outcomes Measurement Information System (PROMIS®) is a set of Patient-Reported Outcomes (PROs) that cover physical appearance, mental health, and social health. The PROMIS has been built through an Item Response Theory approach (IRT), a model-based measurement in which trait level estimates depend on both persons' responses and on the properties of the items that were administered. The aim of this study is to test the psychometric properties of an Italian custom four-item Short Form of the PROMIS Anxiety item bank in a cohort of outpatients with IMIDs., Methods: We selected four items from the Italian standard Short Form Anxiety 8a and administered them to consecutive outpatients affected by Inflammatory Bowel disease ( n = 246), rheumatological ( n = 100) and dermatological ( n = 43) diseases, and healthy volunteers ( n = 280). Data was analyzed through an Item Response Theory (IRT) analysis in order to evaluate the psychometric properties of the Italian adaptation of the PROMIS anxiety short form., Results: Taken together, Confirmatory Factor Analysis and Exploratory Factor analysis suggest that the unidimensionality assumption of the instrument holds. The instrument has excellent reliability from a Classical Theory of Test (CTT) standpoint (Cronbach's α = 0.93, McDonald's ω = 0.92). The 2PL Graded Response Model (GRM) model provided showed a better goodness of fit as compared to the 1PL GRM model, and local independence assumption appears to be met overall. We did not find signs of differential item functioning (DIF) for age and gender, but evidence for uniform (but not non-uniform) DIF was found in three out of four items for the patient vs . control group. Analysis of the test reliability curve suggested that the instrument is most reliable for higher levels of the latent trait of anxiety. The groups of patients exhibited higher levels of anxiety as compared to the control group ( p s < 0.001, Bonferroni-corrected). The groups of patients were not different between themselves ( p = 1, Bonferroni-corrected). T-scores based on estimated latent trait and raw scores were highly correlated (Pearson's r = 0.98) and led to similar results., Discussion: The Italian custom four-item short form from the PROMIS anxiety form 8a shows acceptable psychometric properties both from a CTT and an IRT standpoint. The Test Reliability Curve shows that this instrument is mostly informative for people with higher levels of anxiety, making it particularly suitable for clinical populations such as IMID patients., Competing Interests: Marco Tullio Liuzza is an Academic Editor for PeerJ., (© 2021 Liuzza et al.)

Aims: To evaluate nursing activity through outcomes that are affected, provided, and/or influenced by nurses and defined as nursing-sensitive outcomes in adult IBD patients., Design: Systematic review without meta-analysis., Data Sources: PubMed, Embase, CINAHL, PsycINFO, and the Cochrane Library databases on August 2019., Review Methods: Peer-reviewed articles published between 2000-2020 were reviewed. The outcome measures were contextualized and presented by OMERACT Filter 2.0., Results: Twenty-four studies were included. Eighteen nursing-sensitive outcomes were identified. These outcomes defined eight domains for health intervention, fitting into three core areas (resource use/economic impact, life impact, pathophysiological manifestations). Fifty-three measurement instruments were identified., Conclusions: Through 53 measurement tools, with use of OMERACT framework, 18 nursing-sensitive outcomes in the main 3 core areas were identified, highlighting the multidimensional role of nursing. Further insights are to be carried out to define nursing outcomes included in IBD nursing intervention studies., Impact: These results could serve as a cornerstone for further investigations and validation by a panel of experts to standardizing nursing activity in a multidisciplinary context., (© 2021 John Wiley & Sons Ltd.)

Aims: To explore whether music can reduce anxiety and pain in patients who underwent diagnostic endoscopic examinations in conscious and deep sedation and to assess degree of satisfaction and willingness to repeat the procedure., Design: Prospective study led by nursing., Methods: Between March 2019-June 2019, consecutive outpatients undergoing endoscopic examinations were simple matched into four groups: Group 1: conscious sedation with music; Group 2: conscious sedation without music; Group 3: deep sedation with music and Group 4: deep sedation without music. Ten minutes before the procedure, two trainee nurses applied music. State-Trait Anxiety Inventory was used to evaluate anxiety., Results: Before and at the end of the procedure, patients who listened to music had a lower level anxiety than those who did not listen and, also, reported lower pain intensity during procedure. Only within Group 1 median anxiety, measured after the procedure, is lower than that measured before. In the bivariate logistic regression model, pain and listening to music were independent factors for satisfaction and willingness to repeat procedure., Conclusion: music in digestive endoscopy reduce pain and anxiety in conscious sedation, thus could be used to reduce anxiety in support to conscious sedation leading to lower usage of deep sedation and consequently reduction of costs and adverse events., Impact: Anxiety in digestive endoscopy limits patients' satisfaction. Music in digestive endoscopy as a specific nursing intervention could reduce anxiety of patients. This nursing intervention study confirms positive effect of music in digestive endoscopy. As part of nursing management, the addition of music to daily care practice in digestive endoscopy may reduce anxiety and increase the patient's degree of satisfaction. Use of music could limit deep sedation use in digestive endoscopy with consequent reduction of risks for patients, execution times, and costs of procedures., (© 2020 John Wiley & Sons Ltd.)

Introduction: Inflammatory bowel diseases (IBDs) are a public health issue with over 3.5 million patients in Europe, but the advent of several biologic agents has completely changed their management. Pharmacovigilance is needed to early detect expected/unexpected adverse events (AEs) to assess the safety of drugs in a real-world setting. Aim of this prospective pharmacovigilance study was to evaluate the occurrence of AEs in patients treated with biologic drugs in gastroenterology units in Southern Italy., Methods: All consecutive patients treated with one biologic drug during a 2-years period (2017-2018) in six gastroenterology tertiary units and satisfying inclusion criteria were enrolled. Demographic and clinical characteristics of patients, type of treatment used, therapy discontinuation, failures, switch/swap to another biologic, and possible onset of AEs were collected. Adverse events have been compared to the number of AEs reported in the same centres in the two years before the protocol., Results: Overall, 623 patients (253 females) with Crohn's disease (352; 56.5%) or ulcerative colitis (271; 43.5%) have been included. Infliximab (IFX) was the most commonly used (308, 49.4%), followed by adalimumab (ADA; 215, 34.5%), vedolizumab (VED; 73, 11.7%), golimumab (GOL; 26, 4.2%) and ustekinumab (UST; 0.2%). Ninety-two patients have experienced AEs (14.8%) and 10 serious adverse events (SAEs) (1.6%) were recorded. Adverse events and SAEs have been reported with GOL (7/26; p  = .88), IFX (51/308; p  = .54), ADA (28/125; p  = .40) and VED (6/73; p  = .11), no AEs occurred with UST (0/1)., Conclusion: Overall, considering the low rate of AEs reported and discontinuation from therapy, our data seems to confirm the positive beneficial/risk ratio of biologic treatment for IBDs and provide useful data on biologic drugs in gastroenterology.

Background and objectives : Spreading of SARS-CoV-2 infection from China to countries with a higher prevalence of inflammatory bowel disease (IBD) has generated concern among gastroenterologists and patients. The aim of this survey is to evaluate knowledge about clinical importance of COVID-19, disease management, prevention measures, and anxiety level during pandemic among patients with IBD. Material and methods : From 15th March to 15th April 2020, a questionnaire survey was administered to 200 patients with IBD by email or phone application. The questionnaire consisted of five sections: (1) anthropometric, demographic and clinical characteristics, (2) knowledge about clinical importance of COVID-19, (3) IBD management, (4) prevention measures, (5) anxiety level during pandemic. Results : One hundred forty two questionnaires were completed. Ninety-seven patients (68.3%) were males with a mean age of 46 years (SD 13; range 17-76) . Fifty-four individuals (38%) were affected by Crohn disease and 88 (62%) by Ulcerative Colitis. Most patients reported high knowledge about clinical importance of COVID-19 (80%), IBD management (72%), and prevention measures (97%). Sixty-two percent of them showed moderate-high level of anxiety. High education level was independently associated with high knowledge about clinical importance of COVID-19 (odds ratio [OR] 5, 95% confidence interval [CI] 1.49-16.6, p = 0.009) and older age (OR 1, 95%, CI 1.01-1.1, p = 0.01), while the receipt of e-format educational material with low knowledge about clinical importance of COVID-19 (OR 3, 95%, CI 1.08-9.3, p = 0.03). Displaying an active disease appeared to be independently associated with low knowledge of IBD management (OR 5.8, 95% CI 1.4-22.8, p = 0.01) and no variables other than an older age was independently associated with higher level of anxiety (OR 1.04, 95% CI 1.009-1.09, p = 0.01). Conclusions : High educational level and aging promote knowledge about clinical importance of COVID-19, while e-format educational material does not. Taken together with findings that an active disease status compromises knowledge of IBD management and the high level of anxiety related to increasing age, these data suggest the need of further supporting patient-oriented strategies in IBD during Covid-19 pandemic.

Background: A growing number of functional foods have been proposed to reduce cholesterol levels and the Portfolio Diet, which includes a combination of plant sterols, fibres, nuts, and soy protein, reduces low density lipoprotein cholesterol (LDL-C) from 20% to 30% in individuals with hyperlipidaemia. In this pilot study, the aim was to investigate whether a Mediterranean Diet incorporating a new and simple combination of cholesterol-lowering foods, excluding soy and nuts (namely the Portfolio-Mediterranean Diet), would reduce LDL-C levels, in the short-term, better than a Mediterranean Diet plus a sterol-enriched yogurt or a Mediterranean Diet alone., Methods: We retrospectively evaluated 24 individuals on a Portfolio-Mediterranean Diet and 48 matched individuals on a Mediterranean Diet with or without a sterol-enriched yogurt (24 each groups) as controls., Results: At follow-up (after 48±12 days), we observed an LDL reduction of 21±4, 23±4, and 44±4 mg/dL in the Mediterranean Diet alone, Mediterranean Diet plus yogurt and Portfolio-Mediterranean Diet respectively (P&lt;0.001)., Conclusion: A Portfolio-Mediterranean Diet, incorporating a new combination of functional foods such as oats or barley, plant sterols, chitosan, and green tea but not soy and nuts, may reduce LDL of 25% in the short term in individuals with hypercholesterolemia.

Background and Objectives : Nursing management in Inflammatory Bowel Disease (IBD) is focused on global patient care. Starting from basic knowledge of diagnostic and therapeutic management, nurses can assess the impact of IBD on patients' quality of life not only at the physical level, but also at the psychological, social, and emotional levels. The aim of this study was to evaluate the impact of gastrointestinal symptoms on psychosocial changes in IBD patients in remission through nursing-led Patient-Reported Outcomes. Materials and Methods : We performed a cross-sectional study of 109 IBD patients in clinical and endoscopic remission. Specialist nurses invited patients to complete questionnaires on gastrointestinal symptoms and quality of life through the Patient-Reported Outcomes Measurement Information System (PROMIS). Results : We found that the gastrointestinal symptoms that the patients reported had a significant impact on the analyzed aspects of health. More specifically, belly pain, diarrhea, and bloating were associated with depressive symptoms ( p < 0.001), anxiety ( p < 0.001), fatigue ( p < 0.001), and sleep disturbances ( p < 0.001). Moreover, these symptoms also significantly affected patients' social dimension in terms of satisfaction with participation in social roles ( p < 0.001, p < 0.05, and p < 0.001 for belly pain, diarrhea, and bloating, respectively) and physical functions ( p < 0.001). The results were virtually the same in a multivariable analysis adjusted by age, gender, body mass index (BMI), and disease duration. Conclusions : Even during remission, gastrointestinal symptoms are the main factors that influence quality of life in IBD patients. This exploratory study highlights the need to adopt validated questionnaires in clinical practice, and demonstrates that PROMIS is a valid, objective, and standardized instrument that can help nursing staff to better define the consequences of the disease in a patient's daily life., Competing Interests: The authors declare no conflicts of interest.

Background and Aim: Most studies focused on the benefits of weight loss on hepatic steatosis and no studies have been specifically designed to assess the role of weight gain on the development of liver steatosis in patients affected by inflammatory bowel diseases. The aim of this study was to analyse the relation between weight change over time and liver steatosis in patients with inflammatory bowel diseases., Methods: We retrospectively evaluated a population of 89 ambulatory patients in clinical remission or affected by mild disease, as determined from disease activity indices, with at least one follow-up visit. Transient elastography was used to quantify liver steatosis., Results: A total of 49 individuals (55%) were overweight/obese at baseline. A significant difference in weight change was found between participants that improved, were stable and worsened, over a mean follow-up of four years. (-1.0 kg ± 4; 2.5 kg ± 6; and 5.4 kg ± 5; respectively, p = 0.009). We found a greater probability of worsening in the hepatic fat content in individuals who gained more than 6% of body weight than in those gaining less than this value (log⁻rank (Mantel⁻Cox) χ² test = 9.85; df = 1; p = 0.002)., Conclusions: A body weight gain of 6% increases the probability of deterioration in liver steatosis over a period of four years in patients with inflammatory bowel diseases. Weight gain prevention with lifestyle interventions may be the cornerstone treatment of these patients.

Purpose: Diabetes has been linked to an impaired ability to oxidize fatty acids. Fat oxidation can be assessed clinically by a respiratory quotient measurement during fasting. We hypothesized that a respiratory quotient might predict metabolic syndrome and type 2 diabetes onset. Methods: In this longitudinal study we used an existing database of 233 individuals who had complete nutritional and biochemical data at baseline and after 12-month follow-up. All participants underwent an indirect calorimetry to measure the respiratory quotient. We excluded participants with diabetes, metabolic syndrome, chronic diseases, and those who had changed food habits in the previous 3 months. Only 88 subjects met the inclusion criteria. Results: Two individuals developed type 2 diabetes and 10 metabolic syndrome after 1 year. Participants in the high respiratory quotient group (>0.91) had a higher incidence of metabolic syndrome/diabetes than those in the low quotient group (25 vs. 8% p = 0.04). In this group, mean basal respiratory quotient was 0.97 ± 0.04. In the high respiratory quotient group, Kaplan-Meier curves showed a greater probability of having metabolic syndrome/diabetes than those in the low respiratoryquotient group (log Rank χ 2 -test = 8.44; p = 0.004). A multivariable Cox proportional hazards model demonstrated that energy expenditure and weight increase did not predict metabolic syndrome/diabetes [HR (95% CI) = 1 (0.996-1.005), p = 0.86 and 3.9 (0.407-38.061), p = 0.23, respectively). Conclusions: A greater probability of metabolic syndrome/diabetes was found in individuals with a basal respiratory quotient of >0.91 than in those with a respiratoryquotient of ≤ 0.91 after 1 year. In the short-term anthropometric measurements and their variation overtime were not correlated with metabolic syndrome/diabetes.

Background: Inflammatory bowel disease (IBD) is due to the interaction of genetic and environmental factors that trigger an unbalanced immune response ultimately resulting in the peculiar inflammatory reaction. Experimental models of IBD point to a role of T-cell-derived cytokines (Th17) and to SGK1 as mediator of the Th17 switch. We hypothesize that SGK1, a salt inducible kinase, directs lymphocytic behavior and tissue damage., Methods: Eleven controls and 32 ulcerative colitis (UC) patients were randomized according to endoscopic Mayo score. Mucosal biopsies from different intestinal tracts were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction to check the expression of disease markers including SGK1. Peripheral blood mononuclear cells (PBMCs) from patients and controls were analyzed by fluorescence-activated cell sorting. Finally, an in vitro cell model was developed to test the hypothesis., Results: SGK1 mRNA and protein expression in lesional areas of UC patients were lower than in normal peri-lesional areas of the same patients and in normal tissues of healthy controls. SGK1 expression was increased in PBMCs from UC patients, particularly in the CD4+ cell population, enriched in Th17 cells. IL17/IL13 was increased in patients and correlated with SGK1 expression. Genetically engineered Jurkat cells confirmed the effect of SGK1 overexpression on viability of RKO cells., Conclusions: These observations suggest a pathogenic mechanism whereby SGK1 overexpression in CD4+ T cells induces the secretion of the inflammatory cytokines IL17 and IL13, which downregulate the expression of SGK1 in target tissues. Our data suggest a novel hypothesis in the pathogenesis of UC, integrating colonic epithelial cells and lymphocytes., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Several biologically active molecules including nutrients can affect the vascular endothelium which becomes dysfunctional and, as a consequence, predisposes to atherosclerosis. However, the impact of the intake of sodium and polyunsaturated fatty acids on carotid atherosclerosis in a population of elderly women has scarcely been studied. Our aim was to investigate the association between carotid intima-media thickness and atherosclerotic plaque and nutrient intake in asymptomatic elderly women. Carotid atherosclerosis was determined by duplex ultrasound in 108 elderly women. Dietary intake was assessed by a combination of a 24-hour recall and a 7-day food record. A physical examination and laboratory tests were performed. We found an association between the C-IMT and polyunsaturated fatty acid (negative, B = -0.014; p = 0.03; CI -0.027/-0.001) and sodium (positive, r = 0.16; P = 0.09) intake. When linoleic acid was added to the multivariable regression analysis instead of polyunsaturated fatty acids, C-IMT was associated with linoleic acid (B = -0.017; p = 0.02; CI -0.032/-0.003). In normotensive women we found a positive association between the C-IMT and sodium intake. The atherosclerotic plaque prevalence increased with the increase in sodium intake (66% vs 90% Tertile I vs Tertile III; p = 0.02). Iin conclusion, A low salt diet to a level of about 1.5 g/d and a polyunsaturated fatty acid intake of >9 g/d were found to be associate with a low atherosclerotic plaque prevalence in an elderly female population. Sodium and polyunsaturated fatty acids-mediated functional changes of the carotid endothelium may be implicated in atherosclerosis development., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Unlabelled: Chronic hepatitis C virus (HCV) infection may progress to cirrhosis and hepatocellular carcinoma (HCC). Recently, two genetic variants, DEPDC5 rs1012068 and MICA rs2596542, were associated with the onset of HCC in Asian subjects with chronic HCV infection. The aim of the present study was to analyze whether DEPDC5 and MICA genetic variants were associated with liver disease progression in European subjects with chronic HCV infection. In a Northern Italian discovery cohort (n = 477), neither DEPDC5 rs1012068 nor MICA rs2596542 were associated with HCC (n = 150). However, DEPDC5 rs1012068 was independently associated with cirrhosis (n = 300; P = 0.049). The association of rs1012068 with moderate to severe fibrosis was confirmed in an independent cross-sectional German cohort (n = 415; P = 0.006). Furthermore, DEPDC5 rs1012068 predicted faster fibrosis progression in a prospective cohort (n = 247; P = 0.027). Next, we examined the distribution of nonsynonymous DEPDC5 variants in the overall cross-sectional cohort (n = 912). The presence of at least one variant increased the risk of moderate/severe fibrosis by 54% (P = 0.040). To understand the molecular mechanism underlying the genetic association of DEPDC5 variants with fibrosis progression, we performed in vitro studies on immortalized hepatic stellate cells (LX-2). In these cells, down-regulation of DEPDC5 resulted in increased expression of β-catenin and production of its target matrix metallopeptidase 2 (MMP2), a secreted enzyme involved in fibrosis progression., Conclusion: DEPDC5 variants increase fibrosis progression in European subjects with chronic HCV infection. Our findings suggest that DEPDC5 down-regulation may contribute to HCV-related fibrosis by increasing MMP2 synthesis through the β-catenin pathway., (© 2015 The Authors. HEPATOLOGY published by Wiley Periodicals, Inc., on behalf of the American Association for hte Study of Liver Diseases.)

Background: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels., Methods: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography., Results: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001)., Conclusions: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.

We present clinical cases, which underline some difficulties in diagnosis and treatment of hepatitis C virus (HCV) infection. Case report #1 shows a patient who avoided clinical follow-up for HCV until the development of hepatocellular carcinoma. In this patient, non-invasive procedures did not allow to make a differential diagnosis between hydatidosis and hepatocellular carcinoma but diagnosis was only made with liver biopsy.

Familial adenomatous polyposis (FAP) is one of the most important clinical hereditary forms of inherited susceptibility to colorectal cancer and is characterized by a high degree of phenotypic heterogeneity. We used a mass spectrometry driven-proteomic strategy to identify serum molecules differently expressed in FAP patients. The data obtained were subsequently processed by bioinformatic analysis and confirmed by Western blotting. Significant differences were highlighted in the expression of serum proteins of FAP patients. In particular, two proteins (alpha-2-HS-glycoprotein and apoliprotein D) were down-regulated (about 0.5- and 0.7-fold, respectively) in carpeting versus diffuse FAP patients and healthy donors, while alpha-2-antiplasmin was up-regulated (about 1.4-fold). Moreover, mass spectrometry approach enabled us to identify serum biomarkers specific for two distinct clinical form of FAP, i.e. carpeting and diffuse FAP. In particular, vitronectin was up-regulated (more than 1.4-fold) in diffuse FAP patients versus carpeting FAP and versus healthy donors, and two additional proteins (Haptoglobin and alpha-1-acid glycoprotein 1) were up-regulated in 2 out of 3 carpeting FAP patients. Our study suggests that mass spectrometry combined to a strong bioinformatics analysis is a valuable tool for the identification of quali/quantitative differences in the serum proteome of otherwise indistinguishable FAP phenotypes. Moreover, the definition of a proteomic profile, supported by the supervised classification, is a powerful and highly sensitive approach for the identification molecular signatures that are able to outperform the traditional disease markers and can therefore be efficiently applied for the diagnosis and clinical management of FAP patients.

Ascaris presence in humans has been associated with high levels of blood eosinophils and serum IgE. This study was designed to address the influence of Ascaris infection on allergic and inflammatory parameters of atopic subjects. A cross-sectional design was used, and atopic individuals to be assessed were divided into 3 groups including Ascaris-infected, anti-Ascaris IgG-positive (seropositive), and control subjects. All subjects enrolled had positive skin test reactivity to at least 1 perennial or seasonal allergen; however, levels of C-reactive protein, C3, and C4 were within normal range values. Eosinophil percentage was not significantly different among the groups studied. Total IgE and specific anti-Ascaris IgE levels in the seropositive group were significantly higher than concentrations found in both control and infected groups. Interleukin (IL)-4 release in Ascaris-infected patients was significantly increased versus seropositives, who were able to produce more IL-4 than controls. The levels of IL-10 were lower in the seropositives as well as infected subjects in comparison with controls. CD25(+) lymphocyte populations were significantly increased in the infected group versus the seropositives as well as the controls. Lung function tests of some selected seropositive subjects were significantly impaired. The same parameters of a representative infected patient were not different from controls. Our data on T helper type 2 cells (Th2) and regulatory T cells (Treg) features, as well as CD25(+) lymphocyte increase, suggest an Ascaris-induced mechanism leading to parasite survival. Moreover, the stable control of both T helper type 1 cells (Th1) and Th2 immunity cascades, paralleled by the absence of overwhelming inflammatory systemic reactions and lack of allergic syndromes, may result in a favorable host condition.

The effects of lipid composition and preparation conditions on the physicochemical and technological properties of gemcitabine-loaded liposomes, as well as the in vitro anti-tumoral activity of various liposome formulations were investigated. Three liposome formulations were investigated: DPPC/Chol/Oleic acid (8:3:1 molar ratio, liposomes A), DPPC/Chol/DPPS (6:3:1 molar ratio, liposomes B) and DPPC/Chol/DSPE-MPEG (6:3:1 molar ratio, liposomes C). Multilamellar liposomes were prepared by using the TLE, FAT and DRV methods, while small unilamellar liposomes were obtained by extrusion through polycarbonate filters. Light scattering techniques were used to characterize liposome formulations. Loading capacity and release profiles of gemcitabine from various liposome formulations were also investigated. Caco-2 cells were used to evaluate in vitro the antitumoral activity of gemcitabine-loaded liposomes with respect to the free drug and also the intracellular drug uptake. Preparation methods and liposome lipid composition influenced both physicochemical parameters and drug delivery features. Liposomes with a size ranging from 200 nm to 7 microm were obtained. The gemcitabine entrapment was higher than that expected probably due to an interaction with the liposome lipid components. The following decreasing loading capacity order was observed: liposome B>liposome C>liposome A. Gemcitabine release from various liposome formulations is modulated by two different processes, i.e. desorption from and permeation through liposomal bilayers. MTT assay showed a greater cytotoxic effect of gemcitabine-loaded liposomes with respect to the free drug. The following decreasing anticancer activity order was observed between the various liposome formulations: liposome C>liposome A>liposome B. The increased anticancer activity is correlated to the ability of the colloidal carrier to increase the intracellular drug uptake. Due to the encouraging results and to the high liposome modularity various applications of potential therapeutic relevance can be envisaged for liposomes.

Germline mutations within the mismatch repair (MMR) genes are generally found in colorectal cancer (CRC) patients with a positive family history for the presence of the neoplasia. Clinical standard criteria have been established to define hereditary-non-polyposis-colorectal cancer (HNPCC)-prone families. Interestingly, the number of MMR gene mutations found in kindreds not fulfilling these criteria is still increasing. In this work we report the identification of a novel germline mutation of the hMSH2 gene, in two CRC-bearing subjects. The two probands belong to a large kindred from South Italy with no history suggestive for cancer aggregation. On the other hand, the early-onset of the neoplasia as well as the presence of a high number of tumor infiltrating lymphocytes (TILs) in the histological specimens of both patients, prompted us to perform a comprehensive genetic analysis. This analysis included the evaluation of the microsatellite instability (MSI) status with five markers according to the National Cancer Institute recommendations, followed by direct sequencing of the hMLH1 and hMSH2 genes. Both probands were found to carry a germline missense (277 C>T) mutation leading to the change (L93F) of an amino acid residue in a highly conserved domain of the MSH2 protein. This mutation is accompanied by the loss of expression of the hMSH2 gene in the tumor tissue. Our findings suggest that in the presence of the above-mentioned criteria it may be useful to perform a molecular analysis of the MMR genes, even if the pedigree does not show marked aggregation of cancers.

Objective: To evaluate the effectiveness of gonadotropin-releasing hormone agonists (GnRH-a) with or without coadministration of tibolone in women with menstrual cycle-related irritable bowel syndrome (IBS)., Design: Prospective, randomized, placebo-controlled clinical trial., Setting: Universities of Catanzaro and Naples., Patient(s): One hundred twenty young premenopausal women with menstrual cycle-related IBS (Rome II criteria)., Intervention(s): Administration of leuprolide acetate depot (LAD, 11.25 mg IM/3 months) plus tibolone (group A), LAD plus placebo tablets (group B), and injection of a placebo solution plus placebo tablets (group C)., Main Outcome Measure(s): Severity of bowel symptoms or signs of IBS and quality of life (QoL), at baseline and after 6 months of treatment., Result(s): In all groups, the mean scores for each symptom or sign of IBS and for QoL were significantly improved after treatment. A significant difference was observed between group C and groups A and B. No difference between these last groups was detected in symptoms or signs of IBS. The QoL scores were significantly higher in group A than in group B., Conclusion(s): Gondotropin-releasing hormone agonist administration is effective in women with menstrual cycle-related IBS. The addition of tibolone does not reduce effectiveness compared with agonist alone and increases QoL.

At present, it is unclear what the role is of laparoscopic ovarian diathermy (LOD) and of metformin administration as second-line treatments for ovulation induction in women with polycystic ovary syndrome (PCOS) after failure of clomiphene citrate (CC) treatment. The aim of the present study was to compare in a randomized double-blind placebo-controlled fashion the effectiveness of LOD with metformin administration in the treatment of CC-resistant women with PCOS. A total of 120 overweight primary infertile anovulatory CC-resistant women with PCOS were enrolled and randomized into two groups of treatment. Group A underwent diagnostic laparoscopy, whereas group B underwent LOD. At hospital discharge, the patients were treated for 6 months with metformin cloridrate (group A; 850 mg twice daily) or with multivitamins (group B). The ovulation, pregnancy, abortion, and live-birth rates were evaluated. At the end of the study, the total ovulation rate was not statistically different between both treatment groups (54.8 vs. 53.2% [correction] in groups A and B, respectively), whereas the pregnancy (21.8 [correction] vs. 13.4%), the abortion (9.3 [correction] vs. 29.0%), and the live-birth (86.0 [correction] vs. 64.5%) rates were significantly (P < 0.05) different between the two groups. Our data show that metformin administration is more effective than LOD in overall reproductive outcomes in overweight infertile CC-resistant women with PCOS.

Attention to patient experience and words represents one of factors that contribute to outcome of care. Beginning from a preliminary analysis of characteristics of scientific and common language, this paper means to contribute to reflection about necessity, for nurse and patient, to share illness meaning in order to effectiveness of relationship.

Objective: To evaluate the effectiveness of the injection of bupivacaine plus epinephrine before laparoscopic myomectomy., Methods: Sixty premenopausal women with uterine leiomyomata were enrolled in a randomized controlled design and intraoperatively treated with injection of bupivacaine plus epinephrine (group A) or saline solution (group B) during laparoscopic myomectomy. Uterine size and volume, number of leiomyomata, hematological parameters, total operative time, enucleation time of each myoma, suturing time of the myomectomy, blood loss, degree of surgical difficulty, and postoperative pain were evaluated. Just before and after the injection of vasoconstrictive or saline solution, systolic and diastolic blood pressure and heart rate were recorded in each subject., Results: Blood loss, total operative and enucleation time, and degree of surgical difficulty was significantly (P <.05) lower in group A than in group B. No difference was observed between groups in suturing time of the myomectomy. The number of vials of pain medication used postoperatively was significantly (P <.05) lower in group A than in group B. No differences in systolic and diastolic blood pressure or heart rate was recorded between the 2 groups., Conclusion: The injection of bupivacaine plus epinephrine during laparoscopic myomectomy is effective in reducing blood loss, total operative and enucleation time, degree of surgical difficulty, and postoperative pain.

Background: Our aim was to evaluate the long-term effectiveness and safety of GnRH agonist plus raloxifene administration in women with symptomatic uterine leiomyomas., Methods: Fifty pre-menopausal women with uterine leiomyomas were treated with leuprolide acetate depot at dose of 3.75 mg/28 days and raloxifene hydrochloride at 60 mg/day for 18 cycles. At admission and after each six cycles of treatment, bone mineral density (BMD), uterine, leiomyoma and non-leiomyoma dimensions, serum bone metabolism markers, lipid, glucose and insulin levels were evaluated. Leiomyoma-related and climacteric-like symptoms were assessed using a daily diary., Results: Throughout the study, no significant change in BMD or in any bone metabolism markers was observed. A significant decrease in uterine, leiomyoma and non-leiomyoma sizes was detected in comparison with baseline already after 6 months. No other significant change was observed at the successive follow-up visits. No significant change in lipid and glucose profile was detected throughout the study. The treatments were well tolerated. All treatment withdrawals (16%, eight out of 50) were due to lack of compliance, and none to drug-related adverse experiences., Conclusion: GnRH agonist plus raloxifene administration is an effective and safe treatment for pre-menopausal women with uterine leiomyomas.

This paper presents the outcomes of a research oriented to exploration and description of the motivations and expectations that concur to assumption af an active and intentional role from students engagaged for achievement of knowledges, skills and highly qualitative consistent attitudes with practice of nursing service.

Crohn' s disease (CD) is a chronic intestinal inflammatory disorder characterized by aberrant mucosal Th1 cell activation and production of IL-12, the major Th1-driving factor. The T cell response to IL-12 is dependent on the expression of a specific receptor composed of two subunits, termed IL-12Rbeta1 and IL-12Rbeta2. The content of IL-12Rbeta2, as measured at the mRNA level, is crucial in regulating Th1 differentiation. In this study we therefore investigated IL-12Rbeta2 RNA transcripts in CD. IL-12Rbeta2 expression was increased in active CD as well as Helicobacter pylori (HP)-associated gastritis and Salmonella colitis compared with that in inactive CD, ulcerative colitis, noninflammatory controls, and celiac disease. In contrast, IL-12Rbeta1 transcripts were expressed at comparable levels in all samples. In CD, IL-12Rbeta2 expression strictly correlated with tyrosine phosphorylation of STAT4, a key component of the IL-12-dependent Th1 polarization. This was associated with a pronounced expression of IFN-gamma. Transcripts for IL-12/p40 were detected in CD, HP-positive, and Salmonella colitis patients, but not in celiac disease, indicating that IL-12Rbeta2 up-regulation occurs only in IL-12-associated Th1 gastrointestinal diseases. Finally, we showed that stimulation of lamina propria mononuclear cells with IL-12 enhanced IL-12Rbeta2, suggesting that IL-12 regulates IL-12Rbeta2 expression in human gastrointestinal mucosa. The data show that the signaling pathway used by IL-12 to induce Th1 differentiation is increased at the site of disease in CD, further supporting the view that IL-12/IL-12R signals contribute to the inflammatory response in this condition.

Objective: Several studies support the view that Helicobacter pylori is acquired in early life and within families. However, the exact route of transmission remains unknown. Given that H. pylori colonizes only the human gastric mucosa, the hypothesis that history of vomiting in siblings may be a relevant risk factor was tested in a paediatric setting., Methods: One hundred urban children (age range 0.8-16.6 years, median 9), 44% with evidence of active H. pylori infection, were recruited. A structured questionnaire dealing with socio-economic issues was completed. Vomiting siblings and siblings of vomiting index children were screened for H. pylori by means of (13)C-urea breath test. Serum samples from index children were assayed for immunoglobulin G to hepatitis A (HAV) and Epstein-Barr virus (EBV) in order to check for faecal-oral and oral-oral exposure, respectively., Results: Vomiting siblings of H. pylori-infected index children and siblings of H. pylori-infected vomiting index children had a high rate of active H. pylori infection (60 and 67%, respectively). History of vomiting in siblings was positively associated with active H. pylori infection in the index children (multivariate odds ratio 2.4, 95% confidence interval 1.3-4.3). Seropositivity for HAV and EBV was found in 1 and 68 index children, respectively. The agreement between active H. pylori infection and EBV seropositivity was not significant (kappa = 0.26)., Conclusions: History of vomiting in siblings is an independent risk factor for H. pylori. Nowadays, transmission of H. pylori in urban children may involve the gastro-oral route more than the faecal-oral or oral-oral pathways.

Background: Mesalazine enemas are of well proven efficacy for the topical treatment of distal ulcerative colitis. Although new rectal formulations of mesalazine are not expected to be superior in efficacy and tolerability to standard formulations, they may offer secondary advantages in terms of overall acceptability., Aim: To compare the efficacy, tolerability and overall acceptability of a new mesalazine rectal foam (Salofalk foam) with mesalazine enema in the treatment of active distal ulcerative colitis., Patients and Methods: A multicentre study was carried out in patients with active proctitis, proctosigmoiditis and left-sided ulcerative colitis as evaluated by the Clinical Activity Index (CAI > or =4) and Endoscopic Index (EI > or =6). Patients were randomly assigned to receive, in open-label fashion, either mesalazine foam 2 g twice a day or mesalazine enema (2 g/60 ml twice a day) for 3 weeks. Patients who did not achieve remission (defined as CAI <4 and EI <6) after 3 weeks continued the study receiving the alternative galenic formulation for a further 3 weeks., Results: A total of 195 patients were enrolled. Characteristics at baseline were similar except for concomitant therapy with oral 5-ASA products: during the 1st treatment phase, 41% of patients on enema received such treatment vs only 29% of those on foam. Patients with at least one post-treatment efficacy evaluation were included in the intent-to-treat analysis (n=89 foam, n=96 enema). After 3 weeks of treatment, 112 patients were in remission and only 59 patients entered the 2nd treatment phase thus providing data on acceptability. Remission was achieved after 3 weeks in 54% of patients treated with foam and in 67% of those treated with enema. The 90% confidence interval for the difference in remission rates was 0 to 24 and thus within the clinically acceptable range of therapeutic equivalence. At the end of the 2nd phase, 70% of patients switched to foam were in remission vs 65% to the enema. Two patients discontinued treatment with foam prematurely due to anal burning. No clinically important changes were seen in the laboratory tests., Conclusions: Salofalk foam and enema are equally effective for the treatment of proctitis, proctosigmoiditis and left-sided ulcerative colitis. The new foam preparation is as well tolerated and accepted as enemas and can be used as a therapeutic alternative to conventional mesalazine enema formulations.

Background: An oral-to-oral route of transmission of Helicobacter pylori infection has been postulated, which is supported by the observation that H. pylori is present in the saliva and in dental plaque. On the basis of this assumption, an increased risk of H. pylori infection among dentists was postulated., Method: Serum and salivary H. pylori immunoglobulin (lg)G antibodies were measured in a group of practising dentists. For comparison we also studied a group of controls from the same urban area matched for age, sex, smoking habits, alcohol and non-steroidal anti-inflammatory drug consumption, and history of dyspepsia., Results: There was no significant difference in serum H. pylori lgG antibodies titres between dentists and controls [optical density (OD) 0.991 +/- 0.588 versus 1.025 +/- 0.591, respectively]. Salivary H. pylori lgG were 0.693 +/- 0.726 and 0.661 +/- 0.614 OD in the dentists and control groups, respectively. The frequency of H. pylori-seropositive subjects did not differ between the two groups [22 out of 39 (56%) versus 46 out of 71 (64%)]. A positive saliva assay was found in 23 out of 39 (59%) dentists and in 44 out of 71 (62%) controls. The odds ratio for a dentist being H. pylori-positive was 0.7 (95% confidence interval 0.3-1.7) by serology and 0.9 (95% confidence interval 0.4-2.1) by salivary antibody assay., Conclusion: The data of this study do not support the concept that dentists are a high-risk group for H. pylori infection.

The evidence of a beneficial role of antibacterial drugs in Crohn's disease is largely empirical. Data accumulate to show that these drugs may well be used as an adjunctive therapy to oral anti-inflammatory drugs. Circumstantial evidence has also been provided that antibacterial drugs are effective in relieving symptoms related to bacterial overgrowth and when used for specific indications such as perianal lesions.