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The present study explores the concurrent contribution to sleep problems of individual-related, family-related, and school-related factors in adolescence. Gathering from the Italian 2018 Health Behavior in School-Aged Children (HBSC) data collection, we used hierarchical logistic regression on a sample of 3397 adolescents (51% females, Mage = 13.99, SD = 1.62) to explore the contribution to sleep problems of the individual (Model 1: alcohol use, smoking, screen time, physical activity), familial (Model 2: parental communication, parental support), and school-related (Model 3: peer support, schoolmates/students support, teacher support and school pressure) variables. 28.3 percent of adolescents reported having sleep difficulties. Overall, Model 3 significantly improved over Model 2 and Model 1. Data showed that increasing smoking (OR = 1.11; 95% CI: 1.03–1.20) and screen time (OR = 1.05; 95% CI: 1.02–1.08) were associated with sleep difficulties but not alcohol use and physical activity. Also, impaired communication with both parents and increasing parental support (OR = 0.84; 95% CI: 0.78–0.90) were associated with decreased odds of sleep problems. Finally, both increases in school pressure (OR = 1.40; 95% CI: 1.26–1.56) and lack of student support (OR = 1.25; 95% CI: 1.10–1.42) were associated with a higher likelihood of sleep problems, while peer support and teacher support were not. Conclusion: Our findings highlight the importance of an integrated approach to the study of sleep difficulties in adolescence that includes specific psychosocial contributors such as the quality of parental communication and perceived parental support and considers the quality of the day-to-day relationship with schoolmates and the school level of demands.What is Known:• Adolescents' are at-risk of more significant sleep difficulties, and recent literature highlights the importance of an integrated approach to understanding this phenomenon, including biological, psychosocial, and contextual factors.• The literature lacks findings that consider the concurrent contribution of individual and psychosocial factors to sleep difficulties in adolescence.What is New:• The quality of parental communication and perceived parental support, as expressions of adult figures' emotional and behavioural availability in the adolescent's life, are significant determinants of sleep difficulties.• The quality of day-to-day relationships with schoolmates and the school level of demands contribute to adolescent sleep problems.

Background. Discussion on the impact of pocket money on positive behaviors is still debated.Objective. To investigate the effect of diverse money allowance schemes on risky behaviors (smoking, alcohol, binge drinking, drug use, gambling) during adolescence.Method. 989 students aged 15 from Lombardy (Italy) reported information on money availability in the 2018 wave of the Health Behaviour in School-aged Children study. To analyze the relationship between money availability and risky behaviors we computed odds ratios and 95% confidence intervals through unconditional multiple logistic regression models.Results. Spending more than 10(sic) weekly was associated with higher likelihood to smoke, binge drink or gamble. Receiving pocket money (rather than receiving money upon request) was related to higher likelihood to engage in risky behaviors.Conclusions. Pocket money may have a negative impact on adolescents, particularly with a substantial amount of money. More research is needed to understand why providing money only if needed may serve as a protective factor against risky behaviors.

Background: Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders. Aim: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. Methods: From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available. Results: Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children. Conclusions: There is a need for more, well- designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons.

Introduction: Pain is the most common and distressing medical symptom in hospitalized patients in all wards. Pain prevalence among hospitalized patients is an indicator of the quality of health care. Objective: The aim of this study is to describe pain prevalence in two Italian hospitals. Material and method: This is an observational study. It involved hospitalized patients of both sexes, able and unable to self-report. Descriptive analysis and multivariate analysis were applied. Results: A sample of 754 inpatients were included. In Terni Ho-spital (n = 255), pain prevalence was 80.8%. The mean pain severity was 5.2 (sd ± 3.33). At Rome's San Camillo Hospital (n=499), pain prevalence was 46.9%. Acute pain is more prevalent in women (OR= 0.65; CI 95% 0.43-0.99) and increases with age (OR= 0.97; CI 95% 0.96-0.99). Chronic pain is more prevalent in men (OR= 2.34; CI 95% 1.41-3.97) and increases with age (OR= 1.04; CI 95% 1.03-1.06). Discussion and conclusion.: San Camillo Hospital presents data showing reduced pain prevalence, and describing pain even in patients unable to self-report. It is reasonable to believe that pain control by the staff at San Camillo is better, even though both hospitals are equally important regional institutions.

Yvan Vandenplas,1 Helen A Brough,2– 4 Alessandro Fiocchi,5 Mohamad Miqdady,6 Zakiudin Munasir,7 Silvia Salvatore,8 Nikhil Thapar,9 Carina Venter,10 Mario C Vieira,11 Rosan Meier12,13 1Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium; 2Department Women and Children’s Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 3Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, UK; 4Children’s Allergy Service, Evelina Children’s Hospital, Guy’s and St. Thomas’s NHS Foundation Trust, London, UK; 5Translational Research in Pediatric Specialities Area, Division of Allergy, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, Rome, Italy; 6Department of Pediatrics, Sheikh Khalifa Medical City, College of Medicine & Health Sciences, Khalifa University, Khalifa, United Arab Emirates; 7Department of Child Health, Ciptomangunkusumo Hospital-Medical Faculty Universitas Indonesia, Jakarta, Indonesia; 8Pediatric Department, Hospital “F. Del Ponte”, University of Insubria, Varese, Italy; 9Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Queensland, Australia; 10University of Colorado, Children’s Hospital Colorado, Denver, CO, USA; 11Center for Pediatric Gastroenterology -Hospital Pequeno Príncipe, Curitiba, Brazil; 12Department of Paediatrics, Imperial College, London, UK; 13Department Nutrition and Dietetics, University of Winchester, Winchester, UKCorrespondence: Yvan VandenplasVrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, BelgiumEmail Yvan.vandenplas@uzbrussel.beAbstract: Exclusive breast feeding is recommended in all guidelines as the first choice feeding. Cow milk allergy (CMA) can be diagnosed by a diagnostic elimination diet for 2 to 4 weeks with a hypo-allergenic formula, followed by a challenge test with intact cow milk protein. The most often used hypo-allergenic formula for the diagnostic elimination diet and the therapeutic diet is a CM based extensive hydrolysate. CM-based partial hydrolysates cannot be recommended in the management of CMA because of insufficient efficacy and possible reactions, but about half of the infants with CMA may tolerate a partial hydrolysate. The pros and cons of other dietary options are discussed in this paper. The use of an amino acid-based formula and/or rice based hydrolysate formula during the diagnostic elimination and therapeutic diet is debated. When available, there is sufficient evidence to consider rice hydrolysates as an adequate alternative to CM-based hydrolysates, since some infants will still react to the CM hydrolysate. The pros and cons of dietary options such as soy formula, buckwheat, almond, pea or other plant based dietary products are discussed. Although the majority of the plant-based beverages are nutritionally inadequate, some are nutritionally adapted for toddlers. However, accessibility and content vary by country and, thus far there is insufficient evidence on the efficacy and tolerance of these plant-based drinks (except for soy formula and rice hydrolysates) to provide an opinion on them.Conclusion: A diagnostic elimination diet, followed by a challenge remains the diagnostic standard. The use of an awareness tool may result in a decrease of delayed diagnosis. Breastmilk remains the ideal source of nutrition and when not available a CM extensively hydrolyzed formula, rice hydrolysate or amino acid formula should be recommended. More evidence is needed regarding plant-based drinks.Keywords: amino acid formula, challenge test, cow milk allergy, hydrolysate, plant-based drink, rice hydrolysate, soy formula

Purpose Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. Methods The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). Results The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%,p < 0.001) and NS prostatectomy (58.4% vs. 52.9%,p = 0.04), but received LND less frequently (47.7% vs. 76.7%,p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS >= (4 + 3) and positive cancer cores >= 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. Conclusions PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Purpose The World Health Organization recommends reduction of salt intake to Methods The study population was made of 1270 children and adolescents. Estimates of salt consumption and iodine intake were obtained by measuring 24 h urinary sodium and iodine excretion. Results The iodine intake increased gradually across quartiles of salt consumption independently of sex, age and body weight (p 10.2 g/day). We estimated that approximately 65–73% of the total iodine intake was derived from food and 27–35% from iodized salt and that iodized salt made actually only 20% of the total salt intake. Conclusion In this pediatric population, in face of an elevated average salt consumption, the use of iodized salt was still insufficient to ensure an adequate iodine intake, in particular among teenagers. In the perspective of a progressive reduction of total salt intake, the health institutions should continue to support iodoprophylaxis, in the context of the national strategies for salt reduction. In order for these policies to be successful, in addition to educational campaigns, it is needed that the prescriptions contained in the current legislation on iodoprophylaxis are made compelling through specific enforcement measures for all the involved stakeholders.

The Conoderinae (Coleoptera: Curculionidae) are one of the most distinctive Neotropical weevil groups in behaviour and appearance, attracting numerous hypotheses regarding the evolution and function of widespread apparent mimetic convergence. Conoderines have a poorly documented natural history, and a large fraction of the diversity of the group remains undescribed, presenting challenges to their study. In this analysis, 128 species of conoderine weevils previously or herein hypothesized to belong to three mimicry complexes are analysed in the first quantitative test of conoderine mimicry. Fifteen continuous and categorical characters describing the size, shape and coloration of these weevils were analysed using non-metric multidimensional scaling while statistically testing the resulting clusters in ordination space. Three similar, putatively mimetic complexes are recognized: (1) the ‘red-eyed fly’ complex of weevils, which are hypothesized to be evasively mimetic on various species of red-eyed flies; (2) the ‘striped/spotted’ complex, composed of weevils with a brightly coloured pronotum and red to white elytral stripes or spots; and (3) the ‘shiny blue’ complex of species with iridescent blue to blue–green pronotal scales. Each of these groups covers a wide geographical distribution and has evolved independently in multiple genera, although the red-eyed fly complex appears to be both the most species rich and widely distributed phylogenetically. Groupings were found to be statistically significant, although variation within each group suggests that the similarity in appearance of species in each group could be attributable to independent convergence on different, but phenotypically similar, models. Several avenues for future research on conoderine mimicry are discussed.

OBJECTIVES: The MOSAIC study aimed to evaluate if the Cow's Milk-related Symptom Score (CoMiSS) can be used as a stand-alone diagnostic tool for cow's milk protein allergy (CMPA). DESIGN: Single-blinded, prospective, multicentre diagnostic accuracy study. SETTING: 10 paediatric centres in China. PARTICIPANTS: 300 non-breastfed infants (median age 16.1 weeks) with suspected CMPA. INTERVENTIONS: After performing the baseline CoMiSS, infants commenced a cow's milk protein elimination diet with amino acid-based formula for 14 days. CoMiSS was repeated at the end of the elimination trial. Infants then underwent an open oral food challenge (OFC) with cow's milk-based formula (CMF) in hospital. Infants who did not react during the OFC also completed a 14-day home challenge with CMF. A diagnosis of CMPA was made if acute or delayed reactions were reported. PRIMARY OUTCOME MEASURES: A logistic regression model for CoMiSS to predict CMPA was fitted and a receiver-operator characteristic (ROC) curve generated. An area under the curve (AUC) of =0.75 was deemed adequate to validate CoMiSS as a diagnostic tool (target sensitivity 80%-90% and specificity 60%-70%). RESULTS: Of 254 infants who commenced the OFC, 250 completed both challenges, and a diagnosis of CMPA made in 217 (85.4%). The median baseline CoMiSS in this group fell from 8 (IQR 5-10) to 5 (IQR 3-7) at visit 2 (p

Objectives:The aim of this study was to assess the prevalence of functional gastrointestinal disorders (FGIDs) in children of Mediterranean area using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV and Rome III criteria.Methods:This was a cross-sectional study enrolling children and adolescents living in Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects were examined in relation to the presence of FGIDs, using the Rome IV criteria. Data were compared with the results of a previous study using Rome III data.Results:We analyzed 1972 children ages 4 to 9 years (group A), and 2450 adolescents 10 to 18 years old (group B). The overall prevalence of FGIDs was 16% in group A and 26% in group B, with statistical differences among countries in both groups (P

This is the eighth volume of the Yearbook of Idiographic Science, the editorial project aimed at rethinking idiographic sciences in a new (old) light. This editorial series has been trying over the years to promote reflection, discussions and proposals by researchers and scholars of every background and from around the world. The focus of this volume is health. As in previous editions, it has triggered great ferment, dialogue and debate, as well as elaborations and insights from different points of view. The volume reflects multiple perspectives and many different theoretical approaches—epistemological, medical, philosophical, semiotic, narrative, psychodynamic, hermeneutic, existentialist-phenomenological—and it also collects research reports and psychosocial interventions, extending its interest to a range of different contexts. Despite the fact that it is quite hard to define, health has passed under the scrutiny of a wide spectrum of epistemic instruments.

Objective: The aim of the present study was to assess the prevalence and incidence of pressure ulcers (PUs) in patients hospitalized in a University Hospital in central Italy. Methods: We carried out a prevalence and incidence study on PUs and an additional prevalence estimate of PUs was also produced ten days after the first assessment. All data were explored by descriptive statistics, the Chi-square test and a multivariate analysis. Results: The prevalence of pressure ulcers was of 6,5%, while it increased to 9,9% at the second assessment ten days after the first measurement. Prevalence was statistically significant and increased with the age of inpatients (p=0,004) and was correlated to the origin of the patients (p=0,002). The incidence of PUs ten days after hospital admittance was of 3,6%. Ulcers are more frequently observed in the general medicine rather than in the surgery and intensive care units. Results showed that there exists a meaningful relationship between increased risk (Braden 16) and the presence of PUs, with an OR of 1,40 (95% CI 1,03-1,62) in high risk patients (Braden -12) and with an OR of 1,61 (95% CI 1,06-2,42) in very high or prohibitive risk patients (Braden 13-16). The most affected areas are the sacrum, the heels and the ankles. Mobilization plans were scarcely available, or do not described. Conclusions: The obtained data confirmed the difficulty to measure whether PU prevention practices are being carried out in compliance with the set guidelines presently in use in all the University Hospital Units. There is still a very limited use of available risk assessment tools for predicting PU risk and mobilization plans are still poorly documented. A monitoring and follow-up strategy should be implemented to better understand prevalence and incidence rates.

The hypothesis of a general psychopathology factor (p factor) has been advanced in recent years. It is an innovation with breakthrough potential, in the perspective of a unified view of psychopathology; however, what remains a controversial topic is how its nature might be conceptualized. The current paper outlines a semiotic, embodied and psychoanalytic conceptualization of psychopathology – the Phase Space of Meaning (PSM) model – aimed at providing ontological grounds to the p factor hypothesis. Framed within a more general model of how the mind works, the PSM model maintains that the p factor can be conceived as the empirical marker of the degree of rigidity of the meaning-maker’s way of interpreting experience, namely of the dimensions of meanings used to map the environment’s variability. As to the clinical implications, two main aspects are outlined. First, according PSM model, psychopathology is not an invariant condition, and does not have a set dimensionality, but is able to vary it locally, in order to address the requirement of situated action. Second, psychopathology is conceived as one of the mind’s modes of working, rather than the manifestation of its disruption. Finally, the puzzling issue of the interplay between stability and variability in the evolutionary trajectories of patients along with their life events is addressed and discussed.

This study aims to examine the phenomenon of homicide with victims under 18 years-old in a wide and multiethnic metropoli-tan area in the north of Italy. We’re dealing with a type of crime that generates a widespread alarm and a common concern. The data analysis, approached with a multidisciplinary strategy, presented in this paper is based on forensic reports of the Institute of Legal Medicine of the University of Milan, to provide a detailed framework of the homicides of minors that took place in the territorial jurisdiction of Milan and Monza Prosecutor’s Office between 1993 and 2017. Quantitative and qualitative analysis were conducted regarding victims’ socio-demographic characteristics (gender, age, nationality), weapons used, places and modality of body discovery, murderers, motives of the killing and type of relationship between offenders and victims. Purpose of this paper is to compare the present set of data with the ones provided by the international literature, as well as make some crimi-nological observations on this matter with a view to preventing the phenomenon. To this end, some representative case studies have been added, their characteristics and also the relationships between offender and victim have been discussed.

BACKGROUND The MARTE study investigated the demographic, clinical, and therapeutic characteristics of rheumatoid arthritis (RA) patients ongoing methotrexate (MTX) treatment for longer than 8 years. METHODS This cross-sectional, observational study considered 587 RA patients from 67 Rheumatology Units across Italy. Data collected included demographic, clinical, and therapeutic characteristics, focusing on MTX prescription patterns (route of administration, dosing regimens, treatment duration, and discontinuation). RESULTS As initial therapy, 90.6% of patients received one conventional synthetic Disease Modifying Anti Rheumatic Drug (csDMARD), with treatment started within the first 3 months from diagnosis in half of the patients. MTX was the first csDMARD in 46.2% of patients. The prevalent route of administration at diagnosis was the intramuscular (60.5%), while at study entry (baseline) 57.6% were receiving subcutaneous MTX. Patients who required a higher MTX dose at study entry were those who received a significantly lower starting MTX dose (P

Background: Breast cancer (BC) is the most common female cancer worldwide. Menopausal symptoms are a well-known side effect in women with BC and have a significant negative impact on quality of life (QoL) and sexuality. Nowadays, hormonal replacement therapy and local estrogens are the most common prescriptions to treat vulvovaginal (VVA) symptoms. However, in women with a history of BC, proper therapy for such conditions remains an often inadequately addressed clinical problem. A treatment with microablative fractional CO2 laser (MLT) can produce a remodeling of the vaginal connective tissue without causing damage to the surrounding tissue. The aim of this pilot study is to assess the efficacy and safety of MLT for treating VVA symptoms in women with a history of BC at 20-week follow-up since the first laser treatment. Patients and Methods: Women with BC and VVA symptoms were enrolled in the study and treated with 5 laser applications (one every 4 weeks). The rate of satisfied patients at 20 weeks of follow-up was evaluated with a 5-point Likert scale. Changes of the Vaginal Health Index (VHI) after treatment was compared with baseline. Effects of the laser treatment on VVA symptoms was measured using a 10-cm visual analog scale (VAS). Changes in overall QoL were assessed with a generic QoL questionnaire: the Short Form 12 (SF-12) that we analyzed considering its physical (PCS12) and mental (MCS12) domains. Sexual function was evaluated by the Female Sexual Function Index (FSFI). Results: In this prospective cohort study, we enrolled 40 women with a history of BC and who currently were or (Group 2) who had been (Group 1) on treatment with endocrine therapy for their condition. Six (15.0%) women were very satisfied, 25 (62.5%) were satisfied, 6 (15.0%) were uncertain, and 3 (7.5%) were dissatisfied with the MLT. VVA symptoms and VHI improved significantly at 20 weeks from baseline (P < .05) with no differences between the 2 groups (P > .05). In terms of QoL measured by the SF-12, the PCS12 and the MCS12 significantly improved at the 20-week follow-up. A significant improvement in total FSFI and in all domains was reported in both study groups (P < .05) with no differences between groups (P > .05). Conclusion: MLT was safe and effective in treating VVA symptoms in women with a history of BC, irrespective of being previously or currently on endocrine therapies. © 2021 Elsevier Inc.

Background and Objective: To evaluate the safety and efficacy of transvaginal fractional microablative CO2 laser therapy (MLT) on urinary symptoms in postmenopausal women with genitourinary syndrome of menopause (GSM) in relation to the timing of their onset; if prior to or after menopause. Secondary, the efficacy of MLT on vulvovaginal atrophy (VVA)-related symptoms. Study Design/Materials and Methods: This is a retrospective analysis of prospectively collected data. Postmenopausal women affected by at least one urinary symptom (urinary frequency, urgency incontinence, stress urinary incontinence) and VVA symptom each (dryness, dyspareunia, itching, burning) were enrolled. Our population was divided into two groups in relation to the onset of urinary symptoms, prior to or after menopause. Women were treated with three CO2 MLT laser sessions, administered at a 4-week interval. For urinary symptoms evaluation, we used the following disease-specific questionnaires previously validated in Italy: the Urogenital Distress Inventory score (UDI-6) and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). For each single VVA symptom, we assessed patient's severity perception with a 10-point visual analog scale. Time points of the study were at entry (T0) and at 16 weeks since the first treatment (T1). Collected data were analyzed with the Pearson χ 2 test for categorical variables and the Wilcoxon rank-sum test (for non-normally distributed data), and statistical significance was defined with a P-value 0.05). Secondary, all VVA symptoms showed a statistically significant improvement (P < 0.05) at 16 weeks from baseline; no differences were registered between groups. No adverse events were recorded. Conclusion: This study confirms the safety and efficacy of CO2 MLT for GSM symptoms. When urinary symptoms are considered, it seems that MLT might have a higher efficacy when symptoms started after menopause, in particular when they are part of the OAB syndrome. Lasers Surg. Med. © 2021 Wiley Periodicals LLC. © 2021 Wiley Periodicals LLC

A controlled evolution generated by nonlinear interactions is required to perform full manipulation of a quantum system, and such control is only coherent when the rate of nonlinearity is large compared to the rate of decoherence. As a result, engineered quantum systems typically rely on a bare nonlinearity much stronger than all decoherence rates, and this hierarchy is usually assumed to be necessary. In this work, we challenge this assumption by demonstrating the universal control of a quantum system where the relevant rate of bare nonlinear interaction is comparable to the fastest rate of decoherence. We do this by introducing a novel noise-resilient protocol for the universal quantum control of a nearly-harmonic oscillator that takes advantage of an in-situ enhanced nonlinearity instead of harnessing a bare nonlinearity. Our experiment consists of a high quality-factor microwave cavity with weak-dispersive coupling to a much lower quality superconducting qubit. By using strong drives to temporarily excite the oscillator, we realize an amplified three-wave-mixing interaction, achieving typical operation speeds over an order of magnitude faster than expected from the bare dispersive coupling. Our demonstrations include preparation of a single-photon state with $98\pm 1(\%)$ fidelity and preparation of squeezed vacuum with a squeezing level of $11.1$ dB, the largest intracavity squeezing reported in the microwave regime. Finally, we also demonstrate fast measurement-free preparation of logical states for the binomial and Gottesman-Kitaev-Preskill (GKP) quantum error-correcting codes., Comment: 31 pages, 14 figures

Introduction and hypothesis: Various surgical techniques have been described for vaginal vault prolapse repair, but the best surgical approach is still to be proven. The aim of this study is to report the long-term objective and subjective outcomes of women who underwent iliococcygeus fixation for the treatment of vaginal vault prolapse with a minimum follow-up of 10 years. Methods: Women with symptomatic vaginal vault prolapse (Pelvic Organ Prolapse Quantification [POP-Q] stage ≥ 2) who had previously undergone hysterectomy for any reason were prospectively enrolled and treated with iliococcygeus fixation. Subjective success was defined as Patient Global Impression of Improvement (PGI-I) ≤ 2 and an absence of bulging symptoms. Objective success was defined as stage of prolapse < 2 in all compartments. Overall success rate was defined as women without prolapse symptoms, PGI-I ≤ 2, stage of prolapse < 2, and no need for other surgery. Prolpase Quality of Life (P-QOL) questionnaires were completed at the preoperative visit and at every follow-up visit. Multiple logistic regression was performed to identify factors involved in the risk of recurrent POP. Results: After a median (range) follow-up of 120 (120–132) months, the subjective, objective, and overall cure rates were 82% (32/39), 74.4% (29/39), and 74.4% (29/39), respectively. Only stage IV vault descensus independently predicted POP recurrence after ICG (OR: 7.66 [95% CI: 1.21–9.02]; p < 0.001). Conclusion: Iliococcygeus fixation seems to be a safe and effective option for the treatment of vaginal vault prolapse at 10 years' follow-up. © 2020, The International Urogynecological Association.

Purpose: This study aimed to clarify the efficacy of intravaginal CO2-laser treatment in postmenopausal women with genitourinary syndrome of menopause (GSM). Materials and methods: This double-blind, randomized, sham-controlled trial included postmenopausal women diagnosed with GSM and bothersome dryness and dyspareunia. Treatment consisted of three sessions. Active CO2-laser treatments (active group) were compared to sham treatments (sham group) with the primary endpoints being changes in dryness and dyspareunia intensity, as assessed by the 10-cm visual analog scale. Secondary endpoints were as follows: changes in Female Sexual Function Index (FSFI; total score and all domains), itching, burning, dysuria, and Urogenital Distress Inventory (UDI-6); incidence of symptoms; and presence of adverse events. All outcomes were evaluated at baseline and 4 months post baseline. Results: Fifty-eight women (28 in the active group and 30 in the sham group) were eligible for inclusion. In the active group, dryness, dyspareunia, FSFI (total score), itching, burning, dysuria, and UDI-6 were significantly improved (mean [standard deviation] –5.6 [2.8], −6 [2.6], 12.3 [8.9], −2.9 [2.8], −2.3 [2.8], −0.9 [2.1], and −8.0 [15.3], respectively). In the sham group, dryness, itching, and burning were significantly improved (–1.9 [2], −1.4 [1.9], and −1 [1.9], respectively). All changes were in favor of the active group. After completion of the protocol, the proportion of participants with dryness, dyspareunia, and sexual dysfunction was significantly lower in the active group compared to those in the sham group (all p < 0.005). Conclusions: CO2 laser could be proposed as an effective alternative treatment for the management of GSM as it is superior to sham treatments. © 2020 International Menopause Society.

Confronted with the illness, people live a crisis of continuity of their systems of meaning, of their social and professional routines, of their relational and emotional ties. In general, a person struggling with a disease lives a biographical event of discontinuity that questions her own subjectivity. The traumatic issue from a psychological point of view is mainly due to sudden and unexpected rupture of signifying systems that found the relation between the subject and the external world and to the interruption of processes of temporal continuity of one’s own experience.

This cross-sectional study included postmenopausal women, aged 45-75 years, with the aim to assess the presence of vulvovaginal atrophy (VVA) confirmed by a clinical assessment in the Italian population attending menopausal/gynecological centers. Apart from baseline variables, women scored vaginal, vulvar and urinary VVA symptoms. Impact of VVA on sexual function and quality of life (QoL) was assessed thorough EuroQoL questionnaire (EQ5D3L), Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-revised (FSDS-R). A physical examination was carried out in accordance with routine gynecological practice. VVA was confirmed in 90% of the 1226 evaluable patients (aged 59.0 ± 7.3 years). The prevalence of postmenopausal women with VVA confirmed by gynecological clinical assessment was 75.3%. The patients with VVA confirmed (n = 926) had more severe symptoms (p

Stefano Salvatore,1 Montserrat Espuña-Pons,2 Andrea Tubaro3 1Urogynecology Unit, Obstetrics and Gynecology Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy; 2Urogynecology Unit, ICGON, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain; 3Department of Urology, Sant’Andrea Hospital, Sapienza University, Rome, ItalyCorrespondence: Stefano SalvatoreUrogynecology Unit, Obstetrics and Gynecology Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, ItalyTel +39 02 26432579Email stefanosalvatore@hotmail.comAbstract: Urgency, defined as “a sudden, compelling desire to pass urine which is difficult to defer”, is not always reported by patients with overactive bladder, and is not usually described in these words. Urgency is known to have a strong negative impact on patients’ quality of life and requires attention from healthcare professionals, as they play a key role in establishing the diagnosis and in deciding, together with the patient, the most appropriate treatment. This topic was debated during the symposium “Urinary Urgency: A Symptom in Need of a Cure?”, held at the 11th Annual Meeting of the European Urogynaecology Association (EUGA) in October 2018 in Milan, Italy. The presentation of two clinical cases, those of a young, active woman and a retired teacher, illustrated the importance of this cornerstone symptom and demonstrated how fesoterodine may represent an important option in the management of this condition. The experts concluded that the physician should not leave urgency undeclared or untreated; that the patient should be involved in the choice of treatment; and that fesoterodine, which offers flexible dosing and has proven, consistent positive results on urgency episodes and urgency urinary incontinence, with very low/no risk of impairment of cognitive function, appears to be one of the good choices in the treatment of this symptom.Keywords: antimuscarinic agents, cognitive function, fesoterodine, incontinence, overactive bladder

Come si leggerà nell'Introduzione della sezione propriamente scientifica del Volume, il presente testo nasce dalla volontà e, soprattutto, dall'esigenza culturale di omaggiare il fu Prof. Antonio Fusco. Un debito scientifico ed umano che trova il suo locus naturale in questa prima parte del testo stesso, cui farà poi seguito la parte propriamente scientifica. In siffatta parentesi dovuta per le ragioni appena menzionate, il lettore, l'amico o l'allievo dell'opera del Prof. Fusco potranno trovare un suo sintetico Curriculum Vitae, correlato da una specifica ed accurata prosa, svolta dal già Magnifico Rettore Carlo Cipolli; il quale, oltre che evidenziare, ricordando, i meriti del collega oramai scomparso, aggiunge alsuo scritto un elemento che sarebbe imprescindibile a non trasformare lo stesso in una mera sequenza di parole: l'amicizia e l'affetto per un amico che, oramai, non c'è più. A fine lettura, evidente risuonerà il fatto che la vita di ognuno, se mossa dalla passione per ciò per cui si è predisposti cognitivamente e psicologicamente, può essere ricca di riconoscimenti, riconoscenze e soddisfazioni che, lungi dal divenire un cuscino di allori su cui adagiarsi, per una mente creativa come quella del Prof. Fusco hanno funto solo da motivazioni ad agire instancabilmente guardando sempre al futuro. Il lavoro di una vita che, materialmente, è sancito da un supporto poco più di cm 25x15: una targa. Una materialità evidente che, con grande commozione e riconoscenza, è stata affissa il 25 ottobre 2019 sull'aula fronte l'Aula Magna del Campus "La Folcara", a testimonianza che quello spirito creativo in continua evoluzione non si ferma; non si arresta neppure con la fine biologica di chi lo ha "posseduto". Rimangono le opere ed il pensiero del Prof. Fusco e restano gli affetti. A tal proposito, il lettore troverà una breve e sentita sezione su Testimonianze; coloro i quali hanno avuto modo, nell'arco della vita accademica ed umana, personale, di Fusco di conoscerlo. Ecco, allora, che i ricordi saranno i veri protagonisti di questa parentesi. Dopo di ciò, prima dei contributi prettamente scientifici dei lavori, tenutisi in occasione del Convegno Internazionale Psicologia, Arte, Letteratura. Antiche e Nuove Tendenze, seguiranno i saluti delle autorità che in quei due giorni si sono succedute a rappresentare non solo l'istituzione affiliata, ma anche la relazione di stima e di affetto che le legava al compianto Professore. Si passerà, infine, al volume tradizionalmente inteso.

Background The aim of this study was to define clusters of activity in a population-based cohort during the first 5 years after diagnosis in children with ulcerative colitis [UC] and to identify early prognostic risk factors. Methods All UC patients from the SIGENP IBD registry with a complete follow-up of at least 5 years were included. Active disease was defined every 6 months in the presence of at least one of the following: clinical activity [Paediatric Ulcerative Colitis Activity Index ≥ 35]; endoscopic activity [Mayo score ≥ 1]; faecal calprotectin > 250 µg/g; hospitalization; surgery; or treatment escalation. Formula-based clusters were generated based on four published questionnaire-based activity patterns in adults, plus one additional cluster. Results In total, 226 patients were identified. Forty-two [19%] had moderate–severe chronically active disease, 31 [14%] chronic–intermittent, 75 [33%] quiescent, 54 [24%] active disease in the first 2 years after the diagnosis, then sustained remission, and 24 [11%] a remission in the first 2 years then an active disease. Mild disease onset along with a lower clinical severity not requiring the use of corticosteroids at 6 months were related to a quiescent disease course at the next follow-up (logistic model area under the curve 0.86 [95% confidence interval 0.78–0.94]; positive predictive value 67%; negative predictive value 70%). Eight per cent of patients needed surgery, none in the quiescent group [p = 0.04]. Conclusions More than one-third of children with UC present with a chronically active or intermittent course during the first 5 years of follow-up. A significant group of patients has active disease in the first 2 years and then sustained remission. Interestingly, after initial treatment, one-third of patients have well-controlled disease throughout.

ADAMTS-5 is a major protease involved in the turnover of proteoglycans such as aggrecan and versican. Its aggrecanase activity has been directly linked to the etiology of osteoarthritis (OA), identifying ADAMTS-5 as a pharmaceutical target for OA treatment. However, most existing ADAMTS-5 inhibitors target its active site and therefore suffer from poor selectivity. Here, using a novel approach, we have designed a new class of sugar-based arylsulfonamide inhibitors, which are selective for ADAMTS-5 through binding to a previously unknown substrate-binding site (exosite). Docking calculations combined with molecular dynamics simulations demonstrated that our lead compound is a cross-domain inhibitor that targets the interface of the metalloproteinase and disintegrin-like domains. Targeted mutagenesis identified disintegrin-like domain residues K532 and K533 as an exosite which is critical for substrate recognition. Furthermore, we show that this exosite acts as major determinant for inhibitor binding and, therefore, can be targeted for development of selective ADAMTS-5 inhibitors.

Reviews assessing mirabegron's safety and efficacy, synthesize data from both genders, without providing specific details for female patients with OAB. The aim of this study is to qualitatively and quantitatively synthesize data evaluating mirabegron's use on female patients with OAB. PubMed/Scopus/Cochrane library/Web of Knowledge were searched for full texted, published in English-language and in peer-reviewed journals, up to November 2019, using the keyword “mirabegron”.Jadad score modified by adding allocation concealment, MINORS and RoB were used for the Methodological quality and risk of bias assessment. Twenty-one studies were included in this review;7 RCTs, 3 non-RCTs and 11 observational studies. Controlled trials were of unclear (75%), high (12.5%) or serious risk (12.5%) of bias. Twelve weeks of mirabegron use resulted in significant decrease of urgency, frequency, nocturia and UUI by 1.3–2.2,2.04–2.33,0.42−0.5 and 0.9–1.04 episodes/24 h, respectively. Quality of life and sexual health was improved significantly. Sexual dysfunction decreased from 98% (84/85) at baseline, to 60% (51/85) after 12-weeks of mirabegron (p-value < 0.001). Mirabegron had the same efficacy as anticholinergics in improving all OAB symptoms but with fewer adverse events. Hypertension and antimuscarinics’ effects (i.e dry mouth, constipation) had an incidence of 2% (28/1221) and 1.9% (23/1221) when mirabegron was administered, respectively. Mirabegron is a safe and effective alternative therapy for females with OAB. However, there is a paucity of high-quality RCTs, with large sample sizes, long-term follow-up focusing on mirabegron's comparison to other therapies, quality of life and sexual health of female patients with OAB. © 2020 Elsevier B.V.

Aim: To assess the efficacy and safety of tension-free vaginal tape-obturator (TVT-O) 13 years after implantation for the treatment of female pure stress urinary incontinence (SUI). This is the longest-term evaluation available of TVT-O outcomes. Methods: A multicenter, prospective study was conducted in five tertiary referral centers in three countries. All consecutive women with urodynamically proven pure SUI treated by TVT-O were included. Data regarding subjective outcomes (International Consultation on Incontinence Questionnaire-Short Form, Patient Global Impression of Improvement, and patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Univariable and multivariate analyses was performed to investigate outcomes. Results: One hundred sixty-eight women had TVT-O implantation. At 13 year after surgery, 150 of 157 patients (95%) declared themselves cured (P =.8). Similarly, at 10-year evaluation, 148 of 160 patients (92%) were objectively cured. No significant deterioration of objective cure rates was observed over time (P =.1). The multivariate analysis showed that previous anti-incontinence procedures and obesity independently predicted the subjective (odd ratio [OR]: 6.2 [95% confidence interval [CI], 1.8-13.6]; P =.02 and OR, 1.8 [95% CI, 1.3-3.0]; P =.03, respectively) and objective failure of TVT-O (OR, 5.8 [95% CI, 1.6-13.2]; P =.02 and OR, 1.6 [95% CI, 1.2-3.2]; P =.03, respectively). We found four cases of sling exposure; all of them occurred after the 10-year follow-up. Conclusions: The 13-year results of this study showed that TVT-O is a highly effective and safe option for the treatment of SUI. We found that there is a significantly higher risk of having a sling exposure over 10 years after the procedure; however, the incidence is very low. © 2020 Wiley Periodicals, Inc.

A systematic review and meta-analysis was undertaken to assess the efficacy and safety of intravaginal energy-based therapies (laser and radiofrequency) on sexual health of cancer survivors (CS) (breast cancer (BCS) and/or gynecological cancer (GCS)). PubMed, Scopus, Web of Science, and Cochrane Library were searched until 21/02/2019. Quality of reporting, methodology, and body of evidence were assessed using STROBE, MINORS, and GRADE. Primary outcomes were dyspareunia, dryness, and sexual health (FSFI, FSDS-R). Secondary outcomes were burning, itching, dysuria, incontinence, Vaginal Health Index Score (VHIS), microbiome-cytokine evaluation, and adverse events. Main analyses, subgroup analyses, and sensitivity analyses were performed. Eight observational studies (n = 274) were eligible for inclusion. None of the studies evaluated radiofrequency. BCS and BCS-GCS were included in 87% and 13% of studies, respectively. All primary outcomes improved significantly with the exception of FSDS-R (dyspareunia (5 studies (n = 233), standardized mean difference (StdMD) (− 1.17), 95%CI [− 1.59, − 0.75]; p < 0.001; I2 = 55%), vaginal dryness (4 studies (n = 183), StdMD (− 1.98), 95%CI [− 3.31, − 0.65]; p = 0.003; I2 = 91%), FSFI (2 studies, n = 28, MD (12.79), 95%CI [7.69, 17.89]; p < 0.001; I2 = 0%). Itching, dysuria, and VHIS increased significantly, while burning was not improved. Serious adverse events were not observed by any of the studies. Intravaginal laser therapies appear to have a positive effect on dyspareunia, vaginal dryness, and FSFI of CS. However, the quality of evidence is “very low,” with no data on intravaginal radiofrequency therapy. Further research with high-quality RCTs and long-term follow-up is needed to evaluate the value of energy-based devices as a therapeutic option for CS with sexual problems. © 2019, Springer-Verlag London Ltd., part of Springer Nature.

to investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants.patients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI13, RFS7, acid exposure index7%, total reflux episodes100/24 h in infants or70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age (/12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated.197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS7, and in 17/31 with RSI13. RFS7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index.RSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations.

Little is known about the prevalence of functional gastrointestinal disorders (FGIDs) in children from the Mediterranean area of Europe. We aimed to assess the prevalence of FGIDs in children and adolescents in this region.We collected data on 13,750 children (4-18 years old) enrolled in the Mediterranean-European Area Project, a school-based health study performed in Croatia, Greece, Israel, Italy, Jordan, Lebanon, Macedonia, Serbia, and Spain. Data were collected from March to June and in September of 2016. We analyzed data from 6602 students 4 to 10 years old (group A; mean age, 7.7 ± 1.9 y), and 7148 subjects 11 to 18 years old (group B; mean age, 13.8 ± 2.1 y). Children with FGIDs were identified based on answers to questionnaires on pediatric gastrointestinal symptoms, selected based on Rome III criteria.In group A, the prevalence of FGIDs was 20.7%. The most frequent disorders were functional constipation (11.7%), irritable bowel syndrome (IBS, 4%), aerophagia (3.5%), and abdominal migraine (3.1%). The prevalence of abdominal migraine was significantly higher in girls than in boys (P = .007). In group B, the overall prevalence of FGIDs was 26.6%. The most frequent disorders were functional constipation (13.1%), abdominal migraine (7.8%), aerophagia (6.3%), and IBS (5.6%). In group B, FGIDs had a higher prevalence among girls than boys (P .001). In both groups, we found significant differences in the prevalence of specific disorders among specific countries.In an analysis of data on children 4 to 18 years old from the Mediterranean-European Area Project, we found FGIDs to be more frequent in girls. Functional constipation, aerophagia, abdominal migraine, and IBS are the most common disorders. However, the prevalence of FGIDs varies significantly among countries.

This chapter outlines the implication of the Re.Cri.Re. analysis of European societies’ cultural milieu for policy-making. It is claimed the strategic need of carrying out policies of cultural development, as intended within the Re.Cri.Re. framework, a policy of cultural development is aimed at two main purposes: on the one hand, to define social practices that promote semiotic capital, namely the positive experience of institutions and more in general of the systemic rules; on the other hand, to introduce constraints on the opacification of the system, in order to reduce the deficit of sense it fuels. The chapter is dedicated to outline the purpose and the methodological framework of policies of cultural development as well as to present thirteen suggestions of possible actions of this kind. These suggestions target three broad domains: institutions, economy and vital worlds. In order to clarify the methodological tenets and the suggestion, a few stylized excerpts from case-studies examined during the Re.Cri.Re. project are provided.

Cow’s milk proteins cause allergic symptoms in 2% to 3% of all infants. In these individuals, the physiological mechanism of tolerance is broken with subsequent possible sensitization to antigens, which can lead eventually to allergic responses. The present review aims to provide an overview of different aspects of immune modulation by dietary intervention in cow’s milk allergy (CMA). It focuses on pathogenetic mechanisms of different CMA related disorders, e.g., gastroesophageal reflux and eosinophilic esophagitis, highlighting the role of dietary management on innate and adaptive immune systems. The traditional dietary management of CMA has greatly changed in the last years, moving from a passive approach, consisting of an elimination diet to relieve symptoms, to a “proactive” one, meaning the possibility to actively modulate the immune system. Thus, new insights into the role of hydrolysates and baked milk in immunomodulation are addressed here. Additionally, nutritional components, such as pre- and probiotics, may target the immune system via microbiota, offering a possible road map for new CMA prevention and treatment strategies.