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Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) in children with inflammatory bowel disease (IBD) has been reported only anecdotally. This study aimed at describing the clinical features and outcomes of children diagnosed with both IBD and HLH/MAS. Data on IBD and HLH/MAS characteristics, biochemical, microbiological and genetic assessments, treatments, and outcomes were collected from the Italian Pediatric IBD Registry and presented using descriptive statistics. Out of 4643 patients with IBD, 18 (0.4%) were diagnosed with HLH/MAS, including 12 with ulcerative colitis and 6 with Crohn disease. Among the 18 patients, 7 (39%) had early-onset IBD, but the median age at HLH/MAS diagnosis was 14.0 years (IQR 11.9–16.0). Half of the patients had active IBD at HLH/MAS diagnosis, 11 (61%) patients were on thiopurines, and 6 (33%) were on anti-TNF biologics. An infectious trigger was identified in 15 (83%) patients. One (5%) patients was diagnosed with XIAP deficiency. All patients discontinued thiopurines and 5 (83.3%) discontinued anti-TNF biologics; 16 (80%) patients received steroids for HLH/MAS. Three (17%) patients had a relapse of HLH/MAS. No patient developed lymphoma or died during a median follow-up of 2.7 years (IQR 0.8–4.4). Conclusions: HLH/MAS mainly affects children with early-onset IBD but primarily develops during adolescence, following an infection while on immunosuppressant treatment. Although the prognosis is generally favorable, it is crucial to investigate an underlying immune deficiency. What is known? • Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) is a rare complication of inflammatory bowel disease (IBD). • HLH/MAS has been described in adult patients with IBD while pediatric cases are only anecdotal. What is new? • HLH/MAS primarily develops during adolescence in children with early-onset IBD and its prognosis is usually favorable. • HLH/MAS is generally triggered by an infection in children with IBD who are on immunosuppressant treatment. [ABSTRACT FROM AUTHOR]

An accurate estimation of leakages in water distribution networks is of primary importance for the definition of strategies aimed at ensuring an efficient management of water resources and avoiding water waste. However, in the case of methods based on water balance—such as the Minimum Night Flow method—inaccurate assessment of the minimum night consumption (MNC), e.g. the assumption of fixed MNC values from the literature, can heavily mislead the quantification of leakage level. This study aims at providing insights into the variability of MNC and the related drivers. In greater detail, hourly water consumption data of approximately 200 users are collected over a period of two years and subjected to a multi-phase methodology to obtain a detailed characterization of MNC, with and without considering the users affected by post-meter leakages. The study demonstrates that factors such as seasonality or the presence of post-meter leakages may strongly impact the MNC—the values of which can significantly deviate from the literature references—and thus lead to significant misestimation of network leakages in water systems. Highlights: A methodology for the statistical analysis of minimum night consumption (MNC) based on the daily water-consumption profiles at the user level is proposed. The methodology is applied to hourly-resolution water-consumption data collected over two years in a sample of over 200 users. Occupancy rate, seasonality, and presence of post-meter leakages affect MNC statistics. [ABSTRACT FROM AUTHOR]

Highlights: A method to investigate water consumption based on pressure data is developed. The method exploits the headloss-flowrate equation to obtain water-consumption data. The method is validated on a real case study, resulting in an average error of 2.3%. Limitations affecting the installation of domestic flow meters are overcome. Insights into the features of individual water-consumption events are provided. In the era of digital transformation of water distribution networks, an increasingly important role is played by smart metering technologies, which allow detailed characterization of water consumption up to the end-use (i.e., domestic-fixture) level. To this end, smart flow meters make the collection of water-consumption data at high temporal resolution possible, but their installation can be unfeasible due to technical and economic limitations. As an alternative to the traditional flow-measurement-based methods for end-use characterization, a pragmatic method to obtain information about end-use water consumption exclusively based on pressure data is proposed in this study. In particular, a dual-phase methodology is developed, exploiting (i) pressure data collected at two sections of the user's inlet pipeline and (ii) the pressure-flowrate relationship to discriminate between internal and external water-use events and estimate the household water-consumption time series, which is then subjected to individual-event analysis. The results obtained on a real case study undergone to 1-s resolution pressure monitoring over about one month and a half confirm the method's effectiveness in obtaining the flowrate time series with an average error of about 2.3% and successfully identifying water-consumption events along with their features. [ABSTRACT FROM AUTHOR]

Growing concern surrounds the impact of social media platforms on public discourse1–4 and their influence on social dynamics5–9, especially in the context of toxicity10–12. Here, to better understand these phenomena, we use a comparative approach to isolate human behavioural patterns across multiple social media platforms. In particular, we analyse conversations in different online communities, focusing on identifying consistent patterns of toxic content. Drawing from an extensive dataset that spans eight platforms over 34 years—from Usenet to contemporary social media—our findings show consistent conversation patterns and user behaviour, irrespective of the platform, topic or time. Notably, although long conversations consistently exhibit higher toxicity, toxic language does not invariably discourage people from participating in a conversation, and toxicity does not necessarily escalate as discussions evolve. Our analysis suggests that debates and contrasting sentiments among users significantly contribute to more intense and hostile discussions. Moreover, the persistence of these patterns across three decades, despite changes in platforms and societal norms, underscores the pivotal role of human behaviour in shaping online discourse.Long conversations online consistently exhibit higher toxicity, yet toxic language does not invariably discourage people from participating in a conversation, and toxicity does not necessarily escalate as discussions evolve. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer survivors (BCS) suffer severe vulvo-vaginal atrophy (VVA) and some of the most effective therapies are contraindicated. In literature we have no data about the non-ablative CO2 laser on these women. The aim of this study was to examine its efficacy, safety and acceptability in BCS. Materials and methods: The enrolled women underwent 3 sessions of laser therapy (t0, t1, t2) and a one-month follow up examination (t3). At each time point we measured objective signs of VVA via VHI (Vaginal Health Index) and VuHI (Vulvar Health Index) and subjective parameters (Dryness, Burning, Itching, Dysuria) via visual analog scales (VAS). In sexually active women we evaluated the sexual function with FSFI (Female Sexual Function Index), FSDS (Female Sexual Distress Score) scores and MENQOL (menopause quality of life questionnaire). Results: We enrolled 26 BCS. The mean VHI, VuVHI, dryness and burning VAS scores improved significantly and this improvement was not influenced by the initial VVA grade. MENQOL sexual domain, Lubrication, Orgasm and Pain domains and FSFI total score improved significantly, while Desire, Arousal and Satisfaction domains of FSFI and FSDS did not. At t0 women using Aromatase Inhibitors suffered more severe vaginal dryness than women using Tamoxifen or no therapy, but the three subgroups improved without differences. No adverse event and minimum discomfort were reported. Conclusions: The non-ablative CO2 laser is a safe and effective treatment of VVA and has positive effects on sexual function in BCS regardless the use of adjuvant therapies and the initial grade of VVA. [ABSTRACT FROM AUTHOR]

Introduction: High-density EEG (hdEEG) is a validated tool in presurgical evaluation of people with epilepsy. The aim of this national survey is to estimate diffusion and knowledge of hdEEG to develop a network among Italian epilepsy centers. Methods: A survey of 16 items (and 15 additional items) was distributed nationwide by email to all members of the Italian League Against Epilepsy and the Italian Society of Clinical Neurophysiology. The data obtained were analyzed using descriptive statistics. Results: A total of 104 respondents were collected from 85 centers, 82% from the Centre-North of Italy; 27% of the respondents had a hdEEG. The main applications were for epileptogenic focus characterization in the pre-surgical evaluation (35%), biomarker research (35%) and scientific activity (30%). The greatest obstacles to hdEEG were economic resources (35%), acquisition of dedicated personnel (30%) and finding expertise (17%). Dissemination was limited by difficulties in finding expertise and dedicated personnel (74%) more than buying devices (9%); 43% of the respondents have already published hdEEG data, and 91% of centers were available to participate in multicenter hdEEG studies, helping in both pre-processing and analysis. Eighty-nine percent of respondents would be interested in referring patients to centers with established experience for clinical and research purposes. Conclusions: In Italy, hdEEG is mainly used in third-level epilepsy centers for research and clinical purposes. HdEEG diffusion is limited not only by costs but also by lack of trained personnel. Italian centers demonstrated a high interest in educational initiatives on hdEEG as well as in clinical and research collaborations. [ABSTRACT FROM AUTHOR]

Flow cytometry (FCM) can investigate dozens of parameters from millions of cells and hundreds of specimens in a short time and at a reasonable cost, but the amount of data that is generated is considerable. Computational approaches are useful to identify novel subpopulations and molecular biomarkers, but generally require deep expertize in bioinformatics and the use of different platforms. To overcome these limitations, we introduce CRUSTY, an interactive, user-friendly webtool incorporating the most popular algorithms for FCM data analysis, and capable of visualizing graphical and tabular results and automatically generating publication-quality figures within minutes. CRUSTY also hosts an interactive interface for the exploration of results in real time. Thus, CRUSTY enables a large number of users to mine complex datasets and reduce the time required for data exploration and interpretation. CRUSTY is accessible at https://crusty.humanitas.it/. CRUSTY is an interactive webtool for flow cytometry data analysis, offering popular algorithms and visualizations, and generating publication-quality figures in minutes. It enables users without bioinformatics expertize to mine complex datasets, supports real-time exploration, and is freely available online. [ABSTRACT FROM AUTHOR]

Model-based methods for leakage localization in water distribution systems have recently been gaining more attention. These methods identify the leakage position by comparing the measured network data with the corresponding values simulated by a hydraulic model. In this study two model-based methods already proposed in literature, one based on the Sensitivity Matrix method and the other one on the Linear Approximation method, are analysed and compared to each other. The methods are applied to the same case study network, exploiting only data provided by pressure sensors. Various analyses are undertaken in order to investigate the main critical issues tied to the two methods, i.e. a) the use of different amounts of data averaged over different time windows, b) the impact of the model's accuracy in terms of water demands and pipe roughness, and c) the effect of the number of pressure measuring points. The results show that higher efficiency is obtained by considering the hourly averaged data all together. Moreover, the Linear Approximation method is on average 3 times more accurate than the Sensitivity Matrix when a perfect hydraulic model is used, even with a reduced number of pressure sensors. However, when a hydraulic model and/or measured data affected by errors are considered, the Sensitivity Matrix is more accurate, with an average error almost 10% lower than the Linear Approximation. [ABSTRACT FROM AUTHOR]

Background: The search for biomarkers to evaluate ovarian cancer (OC) homologous recombination (HR) function and predict the response to therapy is an urgent clinical need to improve the selection of patients who could benefit from platinum- and olaparib (poly-ADP ribose polymerase inhibitors, PARPi)-based therapies.Methods: We used a large collection of OC patient-derived xenografts (PDXs) (n = 47) and evaluated their HR status based on BRCA1/2 mutations, BRCA1 promoter methylation and the HRDetect score. RAD51 foci were quantified in formalin-fixed, paraffin-embedded untreated tumour specimens by immunofluorescence and the messenger RNA expression of 21 DNA repair genes by real-time PCR.Results: Tumour HR deficiency predicted both platinum and olaparib responses. The basal level of RAD51 foci evaluated in geminin-positive/replicating cells strongly inversely correlated with olaparib response (p = 0.011); in particular, the lower the foci score, the greater the sensitivity to olaparib, while low RAD51 foci score seems to associate with platinum activity.Conclusions: The basal RAD51 foci score is a candidate predictive biomarker of olaparib response in OC patients as it can be easily translatable in a clinical setting. Moreover, the findings corroborate the importance of OC-PDXs as a reliable tool to identify and validate biomarkers of response to therapy. [ABSTRACT FROM AUTHOR]

Objective: The aim was to assess the awareness and real-life use of biosimilars in inflammatory bowel disease (IBD) among the members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). Methods: An anonymous web survey involving all SIGENP IBD units which can prescribe biosimilars was conducted between July 1st and December 1st, 2020. The questionnaire included 18 questions addressing the most relevant aspects of biosimilars in pediatric IBD, i.e., advantages, disadvantages, costs, traceability, general knowledge, and real-life use. A descriptive analysis of responses was performed. Results: Responses came from 26 pediatric IBD units in Italy, with representation of the North, the Center, and the South of Italy. The majority of participants (n = 20) had spent > 10 years caring for pediatric IBD patients, and worked in a center which had between 100 and 500 registered pediatric IBD patients (n = 14). Most participants (n = 18) reported they were aware that biosimilars have similar efficacy and safety to those of the originator, and all regarded cost-sparing as the main advantage of biosimilars. Most respondents (n = 20) reported they switch from originator to biosimilar in their everyday clinical practice, mostly during the maintenance phase. Most respondents (n = 20) registered no acute adverse events. Nearly all participants felt totally or very confident in using biosimilars. Conclusions: A few years after the introduction of the first biosimilar into the market, real-life data coming from the major IBD units in Italy confirm a favorable and confident position on the use of biosimilars in pediatric IBD. [ABSTRACT FROM AUTHOR]

Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127− CD39hi Trm cells, preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, retains enhanced degranulation capacity compared to the CD127+ CD39lo Trm counterpart ex vivo, and is specifically associated with positive prognosis. Nevertheless, such prognostic benefit is lost in the presence of highly-suppressive CCR8hi ICOShi IRF4+ effector Tregs. Thus, combinatorial strategies aiming at boosting Trm function and infiltration while relieving from Treg-mediated immunosuppression should be investigated to achieve proper tumor control in luminal-like BCs. Losurdo et al analyze breast cancer-infiltrating T cells by single-cell technologies. The find that the extent of infiltration of a small subset of tissue-resident memory CD8+ T cells identify patients with improved survival, highlighting the importance of the specific T cell immune microenvironment. [ABSTRACT FROM AUTHOR]

Functionally, cluster of differentiation 14 (CD14) is a co-receptor of the complex formed by lipopolysaccharide (LPS) and LPS-binding protein expressed on the membrane of a variety of cells. However, CD14 can be shed from the cell membrane into the circulation as soluble CD14 (sCD14) upon cell activation. Previously, our group reported that elevated sCD14 serum levels were associated with the clinical and laboratory findings in the context of visceral leishmaniasis (VL), but not in the context of LPS stimulation or bacterial infection. In the present study, we investigated the secretion dynamics of sCD14 in the context of Leishmania infantum (syn. L. chagasi) in vitro infection. Macrophages from treated VL patients and delayed-type hypersensitivity positive (DTH+) subjects were infected with L. infantum (syn. L. chagasi) promastigotes, and the infection index was evaluated (number of amastigotes per 100 infected macrophages). Additionally, the levels of sCD14, Inteleukin (IL)10, IL-6 and tumour necrosis factor alpha (TNF-α) were measured in the culture supernatants using the Luminex assay. Interestingly, the release of sCD14 was inversely correlated with the L. infantum (syn. L. chagasi) infection index. Of note, the release of sCD14 was upregulated and downregulated in the context of infected macrophages from DTH+ subjects and treated VL patients, respectively. Additionally, we also observed that the levels of sCD14 in the culture supernatants were positively correlated with the levels of TNF-α, IL-6 and IL-10. Therefore, our data suggest that macrophages from treated VL patients and DTH+ subjects respond differently to L. infantum (syn. L. chagasi) infection in the context of the release of sCD14; therefore, the release of sCD14 may be associated with the outcome of VL. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to create standardized protocol for language examination in patients who underwent video-EEG recording and assessed its efficacy in the characterization of ictal language impairment, its ability to differentiate this from impaired awareness, and interobserver reliability in clinical practice. Methods: From our database of video-EEG recordings, we selected a representative sample of 63 focal seizures with presumed language impairment. A multidisciplinary team of epileptologists, EEG technicians, and speech therapists analyzed the selected videos to highlight the critical issues of ordinary ictal language evaluation. We subsequently followed a multi-step process to develop the protocol and assess its interobserver reliability. Results: A protocol based on seven tests in hierarchical succession was created, summed up in the acronym CA-P-S C-A-R-E (Closed Answers, Pro-speak question, Simple orders, Common object denomination, Audio repetition, Reading, Evoke). Following its preliminary administration for 5 months, we assessed the inter-observer reliability of 16 healthcare professionals in distinguishing between language impairment and impaired awareness among a sample of 10 seizures, finding a substantial agreement (kappa 0.61). Conclusion: The proposed protocol, made of simple and easy to memorize tests, is an effective tool that evaluates multiple domains beyond language. Its use could help to recognize ictal aphasia effectively and differentiate it from impaired awareness, minimizing inter-examiner variability. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether prostate cancer (PCa) patients' coping strategies (i.e., fighting spirit, anxious preoccupation, fatalism, helplessness/hopelessness, and avoidance) significantly change during the first 3-year follow-up period of active surveillance (AS). Materials and methods: Altogether, 104 patients on AS completed the Mini-Mental Adjustment to Cancer (Mini-MAC) at baseline (T0), at 10 and 12 months after diagnostic biopsy (T1 and T2, respectively) and then at 24- (T3) and 36-month (T4) follow-up. Paired samples T test was used to detect statistically significant changes over time. Changes ≥ 1 point (or ≤ − 1) were hypothesized to be clinically relevant. Results: During the first 3 years on AS, men experienced decreased anxiety, avoidance thoughts/behaviors, and fight-against-cancer attitudes, and these changes were found to be statistically significant. When considering clinically significant changes between inclusion in AS (T0) and 3-year follow-up (T4), avoidance decreased in 19% of patients. Conclusions: Most patients were observed to have adopted functional coping strategies at baseline, which were maintained through the first 3 years on AS. Overall, men on AS may perceive increasing control over their cancer and comfort with the AS protocol over time and experience slight decreases in anxious preoccupation, cancer-related avoidance thoughts and behaviors, and fight-against-cancer reactions. For those men who find it difficult to cope with AS, psychological monitoring and interventions could be helpful throughout the monitoring journey. [ABSTRACT FROM AUTHOR]

The clinical usefulness of pancreatic elastography (PE) in the assessment of the pancreatic texture before pancreatic resection still remains uncertain. The aims are: to evaluate the value of pancreatic stiffness in both healthy volunteers and patients affected by pancreatic tumor; to evaluate the ability of PE in predicting clinically relevant postoperative pancreatic fistula (CR-POPF). Pancreatic stiffness of healthy subjects was compared with those of pancreatic tumors measuring shear wave velocity (SWV). In the last group, the ability of preoperative SWV in predicting CR-POPF was evaluated using linear regression. Ninety subjects were consecutively enrolled. No difference was found in SWV in the two groups (1.33 ± 0.31 vs 1.26 ± 0.30, p = 0.337). Multivariate analyses showed that male gender was associated with a softer pancreas (OR 0.74, CI 0.55–0.98, p = 0.035). In the 45 patients suitable for a secondary endpoint, the presence of soft pancreas assessed by surgeon's palpation (OR 61.21; CI 2.14– > 1000; p = 0.016) and preoperative risk score (OR 1.72; CI 1.01–2.96; p = 0.049) was predictors of CR-POPF. SWV showed a trend in predicting CR-POPF. The pancreatic stiffness far to the pancreatic neoplasm is the same as healthy controls. SWV showed a trend in predicting CR-POPF but the clinical utility is limited. [ABSTRACT FROM AUTHOR]

In this paper we analyze the effects of the introduction (by either firms or authorities) of a composite good consisting of a fixed proportion of two imperfectly substitutable stand-alone products. First, we find that such a "cocktail" rises the Bertrand equilibrium prices as it introduces a certain degree of complementarity. It also creates incentives to price discriminate and products can be sold at a discount or at a premium (depending on their degree of substitutability) when they are used as part of the composite good. We consider two distinct forms of price discrimination: a traditional one, in which producers set their prices independently of each other and a coordinated one, in which producers cooperate (collude) when setting the price of the composite good. Composite goods might have either a positive or a negative impact on consumer surplus. The sign of the impact depends on the form of price discrimination and consumers tend to be better off if producers coordinate. The impact is also more likely to be positive if "cocktails are done right", i.e., if their quality is high compared to the quality of the stand-alone products. [ABSTRACT FROM AUTHOR]

Objective: During the Covid-19 pandemic, government restrictions limited health care to urgent needs. Neurophysiology centers had to suddenly reschedule their activities, with a lack of specific recommendations about electroencephalography (EEG) execution. During the pandemic phase 1, we launched an online survey to understand the flaws and strengths of the EEG management in Italy at the time of Covid-19 pandemic. Methods: A 45-item online survey (published from April 16 to 30, 2020), endorsed by the Italian Society of Clinical Neurophysiology (SINC), the Italian League Against epilepsy (LICE), and the Italian Association of Neurophysiology technologists (AITN), collected EEG management data (EEG's number and type, indications, personnel and patients safety, devices' sanification) during the Covid-19 pandemic. Results: We received responses from 206 centers. The number of EEGs performed was reduced by 76 ± 20%, and several types of specific EEG (video-EEG, ambulatory-EEG, LTM, polysomnography) were reduced at a minimum. Half of the centers performed inpatient EEGs only for urgencies. Repetitive seizures, encephalitis, and non-convulsive status epilepticus were the most common indications. Covid-19-positive patients received less EEG than negative ones (p < 0.0001). EEG requests came mainly not only from neurologists (n = 176) but also from general practitioners (n = 40), emergentists (n = 79), intensivists (n = 72), and other specialists (n = 53). Those centers which continued performing outpatient EEG examinations were instructed to perform the EEG after a Covid-19-related symptom screening for patients and using personal protective equipment (PPE) through all the procedure. Inpatient EEGs were performed using FFP2/FFP3 masks by neurophysiology technologists in only 50% of cases. Patients executed hyperventilation only for real clinical needs, but often (56%) with a mask. Conclusions: Italian neurophysiology centers strongly adhered to government restrictions of lockdown. Some issues emerged, ranging from the evaluation of a proper indication for EEG, technical procedures of EEG recording, and protection of neurophysiology technicians. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Data regarding possible associations between metabolic syndrome (MS) and pelvic organ prolapse (POP) are scarce. The primary hypothesis was that the prevalence of MS and its components was higher in postmenopausal women with POP than in age-matched women without POP staged with the Pelvic Organ Prolapse Quantification system (POP-Q). The secondary aim of the study was to analyze the association between MS and its components with POP severity. Methods: Presence of MS and its components [elevated triglycerides (TG), waist circumference, blood pressure, and fasting glucose (FG) and decreased high-density lipoprotein cholesterol (HDL-C)] were assessed in 122 women with POP (POP-Q stage I–IV) and 77 without (POP-Q 0). Fasting insulin resistance [homeostasis model assessment for fasting insulin resistance (HOMA-IR)] was also assessed. Results: TG levels, FG, and HOMA index were significantly higher in POP-Q stage I–IV compared with POP-Q 0 (p = 0.04, p = 0.0005 and p = 0.04); HDL-C was significantly reduced in POP-Q stage I-IV compared with POP-Q 0 (p = 0.0003). TG levels (p = 0.0315) were significantly higher in POP-Q stage III and IV vs. POP-Q 0; FG and HOMA-IR (p = 0.0015 and p = 0.0204) were significantly higher in POP-Q stage IV vs. POP-Q 0; HDL-C (p = 0.0047) was significantly lower in all stages vs. POP-Q 0. The prevalence of MS was different between groups (p = 0.04) and higher in POP-Q IV. Elevated TG [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.5–9.3, p = 0.004] and reduced HDL-C (OR 2.0, 95% CI 1.1–3.7, p = 0.0241) significantly increased the risk of POP-Q stage ≥III. Conclusions: MS and its components may be associated with POP. Elevated TG and reduced HDL-C are associated with POP severity. [ABSTRACT FROM AUTHOR]

Zymoseptoria tritici, a globally distributed pathogen, is responsible of Septoria tritici blotch (STB), one of the most damaging wheat diseases. In Italy the incidence of STB has increased during the past few years. The presence of Z. tritici on flag leaves of susceptible durum wheat plants, cultivar San Carlo, after a single artificial inoculation with two inoculum concentrations at different vegetative stages has been evaluated in the plain of Bologna (North of Italy), in a two year field study (2012–2013). The pathogen presence was also assessed in natural infection conditions after a fungicide application in the second year (2013). The results obtained, by visual examination (Incidence, Disease Severity) and DNA quantification by Real time PCR, demonstrated that BBCH 39 (flag leaf stage) is the most susceptible vegetative stage, independently of inoculum concentration and climatic conditions. A good correlation between Disease Severity and DNA quantity was observed in either sampling methods, entire flag leaves and flag leaf discs. Thereafter the most suitable period to obtain the best crop protection with only one fungicide treatment is the flag leaf stage. [ABSTRACT FROM AUTHOR]

This paper presents a comparison of different short-term water demand forecasting models. The comparison regards six models that differ in terms of: forecasting technique, type of forecast (deterministic or probabilistic) and the amount of data necessary for calibration. Specifically, the following are compared: a neural-network based model (ANN_WDF), a pattern-based model (Patt_WDF), two pattern-based models relying on the moving-window technique (αβ_WDF and Bakk_WDF), a probabilistic Markov chain-based model (HMC_WDF) and a naïve benchmark model. The comparison is made by applying the models to seven real-life cases, making reference to the water demands observed over 2 years in district-metered areas/water distribution networks of different sizes serving a different number and type of users. The models are applied in order to forecast the hourly water demands over a 24-h time horizon. The comparison shows that a) models based on different techniques provide comparable, medium-high forecasting accuracies, but also that b) short-term water demand forecasting models based on moving-window techniques are generally the most robust and easier to set up and parameterize. [ABSTRACT FROM AUTHOR]

The orexin-immunoreactive neurons are part of an important arousal-promoting hypothalamic population. Several groups have investigated these neurons during the lactation period, when numerous physiological alterations occur in the dam’s body to cope with the newly acquired metabolic needs of the litter. Although those studies have probed this population during the early and intermediate stages of lactation, few works have examined its response to weaning, including the cessation of the tactile suckling stimulus as the litter stops nursing. Using double immunohistochemistry for orexin and FOS combined with three-dimensional reconstruction techniques, we investigated orexin-synthesizing neurons and their activation at different times during weaning, in addition to the role played by the suckling stimulus. We report here that weaning promoted a decline in the anterior population of orexin-immunoreactive neurons and decreased the number of double orexin-FOS neurons labeled in the central dorsomedial hypothalamus, in addition to reducing the overall number of FOS-immunoreactive cells in the whole tuberal hypothalamus. Disruption of the suckling stimulus from the pups impaired the decrease in the number of anteriorly located orexin-immunoreactive neurons, attenuated the activation of orexin-synthesizing cells in the dorsomedial hypothalamus and reduced the number of FOS-immunoreactive neurons across the tuberal hypothalamus. When taken together, our data suggest that the weaning period is necessary to restore neurochemical pathways altered during the lactation period and that the suckling stimulus plays a significant role in this process. [ABSTRACT FROM AUTHOR]

Objectives and design: We investigated the effect of balanced (BS) and unbalanced (UBS) solutions in the absence or presence of hydroxyethyl starch (HES) on neutrophil functionality, evaluating the release of matrix metalloproteinase (MMP)-9, myeloperoxidase (MPO), and MMP-8. Materials and methods: Neutrophils were isolated by gradient centrifugation and dextran sedimentation and incubated in BS or UBS without or with HES, in the absence or presence of Interleukin-8 (IL-8) or Lipopolysaccharide (LPS). MMP-9, MPO, and MMP-8 were assayed by commercially available ELISA kits. Results: There was not any influence of volume replacement solutions on the release of the enzymes from resting neutrophils. After IL-8 stimulation, the release of MMP-9 was higher in BS than in UBS or RPMI-1640, whereas HES enhanced its release regardless of the composition. After LPS stimulation, the release of MMP-9 was higher in both UBS and BS than RPMI-1640, but HES brought its release back to physiological conditions. No difference was found in the release of MPO and MMP-8 after stimulation with IL-8 or LPS. Conclusion: Volume replacement solutions might have an impact on the release of MMP-9 depending on the inflammatory milieu, suggesting that the use of balanced or unbalanced solutions is not a neutral choice. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the acute effect of hyperoxemia on the comfort and the respiratory variables in patients undergoing pressure support ventilation (PSV) for acute respiratory failure (ARF).Design and Setting: Prospective, observational study performed in the intensive care unit of a university hospital.Patients: Thirteen semirecumbent patients were ventilated in PSV mode, the setting of which was established by the treating physician who was blinded to the study.Measurements: The variables measured at different levels (21-80%) of FiO(2) randomly applied were: minute volume (V (E)), respiratory frequency (f) and the pressure develing during the first 100 ms of an occluded breath (P(0.1)). These variables were firstly measured at the level of FiO(2) chosen by the treating physician. Severity of dyspnea was rated using the visual analogue scale 15' after each FiO(2) variation.Results: Modulation of FiO(2) was able to vary significantly the respiratory variables, since a FiO(2) increase was associated with a decrease in dyspnea, P(0.1), f, and V (E). While valuable variations were detected at both lower and higher values of FiO(2) than those established by the treating physician, a significant improvement in the respiratory variables was detected at FiO(2) 60%. The reduction in respiratory drive was statistically related to an amelioration of dyspnea (R(2)=0.89) even at values of FiO(2) higher than 60%.Conclusions: During PSV the respiratory drive can be heavily modulated by varying the FiO(2) since even at FiO(2) greater than 0.6 dyspnea and respiratory variables continued to improve. [ABSTRACT FROM AUTHOR]

This paper compares different recently proposed methods for pressure-driven snapshot simulations of water distribution networks using the EPANET software interface and proposes a new one. The proposed method is based on the insertion of a sequence of devices consisting of a General Purpose Valve (GPV), a fictitious junction, a reach with a check valve and a reservoir at each water demand node. The proposed method differs from other methods previously proposed in the literature - and similarly based on the insertion of sequences of devices consisting of a valve and a reservoir or emitter - in that it uses a GPV; more specifically, for this valve the user can fix the relationship between outflow discharge (or the flow delivered to users) and the available pressure head at the node, thus allowing for a flexible representation of the relationship between these two parameters, whereas with the other methods this relationship remains fixed, based on the structure of the sequence of devices used. Practical applications to three different real-life cases show the unreliability and limits, in terms of accuracy, of some of the methods previously proposed in the literature. They also show, by contrast, the validity of the new method, which has proven to be reliable and accurate, as well as flexible, since it enables any relationship to be defined between the delivered flow and available head. [ABSTRACT FROM AUTHOR]

Objective: Elective abdominal aneurysm repair can be performed by using the transperitoneal or the retroperitoneal approach. The latter has been described as having a better outcome, reducing the impairment of respiratory function or the incidence of lung complications. Hence, the retroperitoneal approach has been proposed for treatment of medically high-risk patients. However, the superiority of one technique or the other in preserving pulmonary function has not been conclusively demonstrated. The aim of this study was to ascertain whether the retroperitoneal and the transperitoneal approaches affect respiratory function differently.Design: A prospective randomized study.Setting: Two four-bed surgical-medical ICUs of a University hospital.Patients: Twenty-three consecutive patients undergoing abdominal aortic aneurysm repair were randomized to the retroperitoneal (12 patients) and transperitoneal approach (11 patients). They were studied: a). within 30 min the end of surgery; b). 8 h after the end of surgery; and c). during a T-piece tube-weaning trial.Measurements: The comparison between the two groups was based on respiratory mechanics, partitioned between lung and chest wall components, basic spirometry, tension-time index of the inspiratory muscle, weaning indexes, and length of stay both in ICU and hospital.Results: The two surgical techniques do not differ in their impact on either respiratory mechanics or inspiratory muscle function or weaning indexes. However, there was a tendency for retroperitoneal patients to stay for less time both in ICU and in the hospital.Conclusions: During the first 24 h after surgery, the postoperative impairment of respiratory function is independent of the surgical approach. [ABSTRACT FROM AUTHOR]

Objective: Although computerized methods of analyzing respiratory system mechanics such as the least squares fitting method have been used in various patient populations, no conclusive data are available in patients with chronic obstructive pulmonary disease (COPD), probably because they may develop expiratory flow limitation (EFL). This suggests that respiratory mechanics be determined only during inspiration. Setting: Eight-bed multidisciplinary ICU of a teaching hospital. Patients: Eight non-flow-limited postvascular surgery patients and eight flow-limited COPD patients. Intervention: Patients were sedated, paralyzed for diagnostic purposes, and ventilated in volume control ventilation with constant inspiratory flow rate. Measurements: Data on resistance, compliance, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) obtained by applying the least squares fitting method during inspiration, expiration, and the overall breathing cycle were compared with those obtained by the traditional method (constant flow, end-inspiratory occlusion method). Results and conclusion: Our results indicate that (a) the presence of EFL markedly decreases the precision of resistance and compliance values measured by the LSF method, (b) the determination of respiratory variables during inspiration allows the calculation of respiratory mechanics in flow limited COPD patients, and (c) the LSF method is able to detect the presence of PEEPi,dyn if only inspiratory data are used. [ABSTRACT FROM AUTHOR]

Aims of this study were to evaluate: (1) whether upper gastrointestinal endoscopy (UGE) is used appropriately according to the American Society for Gastrointestinal Endoscopy (ASGE) and British Society of Gastroenterology (BSG) guidelines in a hospital setting and (2) whether there is any relationship between appropriateness of UGE and the presence of lesions detected by endoscopy. Indications and endoscopic findings for 734 consecutive UGE performed in 697 inpatients were retrospectively evaluated using ASGE and BSG guidelines to determine appropriateness of referrals. UGE showing endoscopic findings that had direct therapeutic or prognostic consequences were classified as "positive"; the other UGEs were classified as "negative." In all, 46% of UGEs were "positive," 54% "negative," and 61.7% and 23.2% of UGEs were inappropriate according to ASGE and BSG guidelines, respectively (P < 0.001). The probability of finding a positive endoscopy was significantly higher in UGE rated as appropriate than in those rated as inappropriate on the basis of ASGE guidelines (P < 0.001), but not on the basis of BSG guidelines. Endoscopies rated as inappropriate according to ASGE and BSG criteria showed a positive finding in 37.3% and 42.3% of cases, respectively (not significant difference). Multivariate analysis showed that the positive finding is directly related to age (P < 0.05), male gender (P < 0.001), prior UGE (P < 0.05), hematemesis (P < 0.001), and inversely related with upper abdominal pain (P < 0.01) and dyspepsia (P < 0.05). In hospitalized patients, UGE is frequently used for inappropriate indications, according to both ASGE and BSG guidelines. However, the actual clinical usefulness of appropriateness criteria, such as those proposed by ASGE and BSG, is questionable, as their strict observance could lead to missing a large number of significant endoscopic findings. [ABSTRACT FROM AUTHOR]

Objective: In chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF), bronchodilating agents administered by inhalation have, in general, little effect on dynamic hyperinflation and concurrent static intrinsic positive end-expiratory pressure (PEEPi,st). Since in COPD the severely obstructed segments of the lung may not be reached by inhaled medication, we reasoned that drug efficiency may be enhanced by intravenous administration of the agent. Design: Physiological study. Setting: Two four-bed surgical-medical ICUs of a university hospital. Patients: Fourteen COPD patients were studied within 36 h from the onset of ARF. Measurements and results: Static compliance (Cst,rs), minimal (Rmin,rs) and additional (ΔRrs) resistance of the respiratory system, and PEEPi,st were measured before and after intravenous administration of salbutamol. All patients had limitation of air flow before and after salbutamol administration. On average, after salbutamol there was a small, though significant, decrease in Rmin,rs (-9%), ΔRrs (-12%) and PEEPi,st (-8%). Conclusion: The changes in resistance and PEEPi,st after intravenous administration of salbutamol were too small to be of clinical significance. [ABSTRACT FROM AUTHOR]

Objective: To validate two instruments measuring quality of life (QOL) suitable for patients admitted to the intensive care unit (ICU): QOL-IT and QOL-SP.Design: Prospective study using patient interviews.Setting: Two four-bed surgical-medical ICUs in a 960-bed teaching hospital.Patients and Methods: One hundred seventy-two adult, co-operative patients consecutively admitted to ICU for more than 24 h were interviewed. One year after hospital discharge, 84 survivors were interviewed again. Inter-observer reproducibility was investigated in 36 patients. To validate the instruments, the QOL-IT and QOL-SP scores reported by patients were considered according to the functional limitation evaluated by the interviewer. Moreover, the theoretical prediction that patients with chronic diseases should have a worse QOL before ICU admission than patients with only acute illness was tested. QOL-IT and QOL-SP scores given 1 year after hospital discharge were compared with those recorded at the first interview.Results: Inter-observer reproducibility was excellent. The possible range of QOL-IT is 0-20 and that of QOL-SP 0-29. According to the functional limitation (absent, mild or severe), the median QOL-IT score increased from 3 to 6 to 13 and QOL-SP from 2 to 6 to 12 (p< 0.0001). The patients with chronic diseases gave scores significantly higher than the patients with only acute illness (median QOL-IT 8 versus 3, p< 0.013; QOL-SP 8 versus 4, p< 0.004). The median QOL-IT score changed from 3 to 4 one year after hospital discharge, a difference which is statistically (p< 0.001), but not clinically, significant. The median QOL-SP score was 3 and did not change.Conclusions: QOL-IT and QOL-SP are instruments able to discriminate between different health states. [ABSTRACT FROM AUTHOR]

Electrophysiological assessment provides valuable information on physiological and pathophysiological characteristics of human swallowing. Here, new electrophysiological measures for the evaluation of oropharyngeal swallowing were assessed: (1) the activation pattern of the submental/suprahyoid EMG activity (SHEMG); (2) the reproducibility of the oral and pharyngeal phases of swallowing, by calculating the similarity index (SI) of the SHEMG (SI-SHEMG) and of the laryngeal-pharyngeal mechanogram (SI-LPM) during repeated swallows; and (3) kinesiological measures related to the LPM. An electrophysiological-mechanical method for measuring the activation pattern of the SHEMG, the SI-SHEMG, and the SI-LPM, and maximal LPM velocity and acceleration during swallowing was applied in 65 healthy subjects divided into three age groups (18-39, 40-59, 60 years or over). All the measures were assessed during three trials of eight consecutive swallows of different liquid bolus volumes (3, 12, and 20 ml). A high overall reproducibility of oropharyngeal swallowing in healthy humans was recorded. However, while values of SI-SHEMG were similar in all the age groups, the SI-LPM was found to fall significantly in the older age group. Both the SI-SHEMG and the SI-LPM were found to fall with increasing bolus volumes. The activation pattern of the SHEMG and the LPM kinesiological measures were differently modified by bolus volume and age in the older subjects with respect to the others. We describe a new approach to the electrophysiological study of swallowing based on computed semi-automatic analyses. Our findings provide insight into some previously uninvestigated aspects of oropharyngeal swallowing physiology, considered in relation to bolus volume and age. The new electrophysiological measures here described could prove useful in the clinical setting, as it is likely that they could be differently affected in patients with different kinds of dysphagia. [ABSTRACT FROM AUTHOR]

A procedure for optimal design of District Metered Areas (DMAs) within a water distribution network based on a multilevel balancing and refinement algorithm to partition the network and determine the optimal meter positions, coupled with a pressure driven hydraulic simulator to quantify the hydraulic performance of the districtualized system, is presented. Unlike other procedures based on graph partitioning techniques proposed in the scientific literature, the two main issues involved in the design of the DMAs, namely a) how to partition the nodes into the required number of districts, and b) which pipes linking districts to leave open, and fitted with an assigned number of flow meters, and which to close, are simultaneously resolved. The application of this procedure to a real case shows that this approach provides design solutions well adapted to different numbers of measuring points, yielding superior performance indicator values to similar procedures reported in the literature and used here for comparative purposes. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Several immune-mediated gastrointestinal disorders, including celiac disease (CD), are associated with neuroendocrine cell hyperplasia. However, neuroendocrine cells have never been explored in refractory CD (RCD).METHODS:Serial duodenal sections from 17 patients with RCD (6 type 1 and 11 type 2), 16 uncomplicated CD patients before and after gluten-free diet, 14 patients with potential CD, 27 patients with non-CD villous atrophy, i.e., common variable immunodeficiency (n=12), Whipple's disease (n=10) and giardiasis (n=5), and 16 healthy subjects were processed for the immunohistochemical detection of chromogranin A (CgA), serotonin, and somatostatin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative reverse transcription-PCR. Serum CgA and 24-h urine 5-hydroxyindoleacetic acid (5-HIAA) were assessed. Biopsies from treated CD patients were cultured with serotonin or peptic tryptic digest of gliadin (PT-gliadin), and interferon (IFN)-γ was detected by ELISA in culture supernatants.RESULTS:Epithelial cells positive for CgA and serotonin, but not somatostatin, were significantly increased in RCD. Raised mucosal transcripts of TpH-1, but not SERT, were found in RCD. On biopsies from treated CD patients, serotonin upregulated IFN-γ production at levels comparable to those induced by PT-gliadin. Serum CgA, but not urine 5-HIAA, was increased in RCD. No significant difference was found between RCD type 1 and type 2 in terms of neuroendocrine cells, mucosal TpH-1 transcripts, and serum CgA.CONCLUSIONS:Serotonin-producing neuroendocrine cells are increased in RCD mucosa. IFN-γ upregulation induced by serotonin suggests that this monoamine may have a role in sustaining the local inflammatory response in CD. [ABSTRACT FROM AUTHOR]

Immunoglobulin G antibodies against deamidated gliadin peptides are now known to have diagnostic accuracy comparable to tissue transglutaminase and endomysium autoantibodies in patients with coeliac disease. However, little is known about their predictive value in infants with a suspected gluten enteropathy. We tested whether deamidated gliadin immunoglobulin G antibodies are more reliable than traditional tests for coeliac disease screening in infancy. Sixty-five children under 2 years of age (42 with malabsorption, 23 controls) were tested for deamidated gliadin immunoglobulin G, tissue transglutaminase and endomysium immunoglobulin A, and gliadin immunoglobulins A and G . Thirty-seven of the 42 children with malabsorption had deamidated gliadin antibodies, associated with tissue transglutaminase and endomysial antibodies in 33, and with gliadin immunoglobulins A and G in 21 and 29, respectively. Intestinal biopsy was performed in 34 of the 37 children positive for deamidated gliadin antibodies. Thirty-two/34 showed villous atrophy consistent with coeliac disease, while the remaining two had a Marsh 1 and a normal mucosa, respectively. Only gliadin immunoglobulins A (4.3 %) and G (39.1 %) were found in controls. The sensitivity of deamidated gliadin, tissue transglutaminase and endomysial antibodies for coeliac disease was significantly higher than that of gliadin immunoglobulins G and A. High titre deamidated gliadin antibodies correlated with severe intestinal damage. Deamidated gliadin antibodies showed a higher diagnostic accuracy for coeliac disease than gliadin antibodies in infancy. High titre deamidated gliadin antibodies predict a severe gluten-dependent duodenal damage. [ABSTRACT FROM AUTHOR]

Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies. Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein?U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies. [ABSTRACT FROM AUTHOR]