257 research outputs found

    Risks of hospitalization and drug consumption in children and young adults with diagnosed celiac disease and the role of maternal education: A population-based matched birth cohort study

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    Background: Celiac disease (CD) may affect healthcare use in children and young adults. Socio-economic factors may act as a confounder or effect modifier. We assessed such hypotheses in a population-based birth cohort of young celiac subjects and references matched by maternal education. Methods: The cohort included all newborns recorded in the Medical Birth Register of Friuli-Venezia Giulia Region (Italy) between 1989 and 2011. CD incident cases were identified through pathology reports, hospital discharges and copayment exemptions and matched with up to five references by sex, year of birth and maternal education. Cox regression models were used to estimate Hazard Ratios (HRs) for major causes of inpatient diagnosis and drug prescription occurring after diagnosis in CD patients compared to references, stratifying by time of first event and maternal education. Results: We identified 1294 CD cases and 5681 references. CD cases had a higher risk of hospital admission for any cause (HR: 2.34; 95 % CI 2.08-2.63) and for all major ICD9-CM categories except obstetric complications, skin and musculoskeletal diseases, and injuries and poisoning. Prescription of all major ATC drug categories, except dermatologicals and genito-urinary medications, was significantly increased in CD subjects. For most outcomes, HRs were highest in the first year after CD diagnosis but remained significant after five or more years. HRs were similar across different categories of maternal education. Conclusions: Diagnosed CD subjects had a higher risk of hospitalization and medication use compared to the general population, even five or more years after diagnosis, with no effect modification of maternal education

    Increased cancer risk in patients undergoing dialysis: a population-based cohort study in North-Eastern Italy

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    open116noBACKGROUND: In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. METHODS: A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998-2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15-1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42-2.45 for age 40-59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89-10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06-4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46-2.22), oral cavity (SIR = 2.42, 95% CI: 1.36-4.00), and Kaposi's sarcoma (SIR = 10.29, 95% CI: 1.25-37.16). CONCLUSIONS: The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.openTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Sarah Shalaby, Raffaella Petrara, Patrizia Burra, Giacomo Zanus, Stefano Zanini,Paolo Rigotti; Maria Rendina, AlfredoDi Leo, Francesco Paolo Schena, Giuseppe Grandaliano, Marco Fiorentino, Augusto Lauro, Antonio Daniele Pinna, PaoloDi Gioia, Sara Pellegrini, Chiara Zanfi, Maria Piera Scolari, Sergio Stefoni, PaolaTodeschini, Laura Panicali, Chiara Valentini, Umberto Baccarani, Andrea Risaliti, Gian Luigi Adani, Dario Lorenzin, Giuseppe Maria Ettorre, Giovanni Vennarecci,Marco Colasanti, Manuela Coco, Fabrizio Ettorre, Roberto Santoro, LuciaMiglioresi, Francesco Nudo, Massimo Rossi,Gianluca Mennini, Luca Toti, GiuseppeTisone, Annachiara Casella, Laura Fazzolari, Daniele Sforza, Giuseppe Iaria,Carlo Gazia, Chiara Belardi, ClaudiaCimaglia, Alessandro Agresta, Gianpiero D’Offizi, Ubaldo Visco Comandini,Raffaella Lionetti, Marzia Montalbano, Chiara Taibi, Giovanni Fantola, Fausto Zamboni, Gian Benedetto Piredda,Maria Benigna Michittu, Maria Gavina Murgia, Bruno Onano, Lucia Fratino, Luigino Dal Maso, Paolo De Paoli, Diana Verdirosi,Emanuela Vaccher, Francesco Pisani, Antonio Famulari, Federica Delreno, Samuele Iesari, LindaDe Luca, Maurizio Iaria, Enzo Capocasale,Elena Cremaschi, Silvio Sandrini, Francesca Valerio,Valentina Mazzucotelli, Nicola Bossini, Gisella Setti, Massimiliano Veroux, Pierfrancesco Veroux, Giuseppe Giuffrida,Alessia Giaquinta, Domenico Zerbo, GhilBusnach, Laura Di Leo, Maria Luisa Perrino, Marialuisa Querques, ValerianaColombo, Maria Chiara Sghirlanzoni , Piergiorgio Messa, Antonio Leoni , Laura Galatioto, Salvatore Gruttadauria, Vito Sparacino, FlaviaCaputo, Barbara Buscemi ,Franco Cit-terio, Gionata Spagnoletti, Maria Paola Salerno, Evaldo Favi Giuseppe Paolo Segoloni, Luigi Biancone, AntonioLavacca, Maria Cristina Maresca, CarmeloCascone, Bice Virgilio, Donato Donati, Fiorella Dossi, Andrea Fontanella, Andrea Ambrosini, Marco Di CiccoTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Shalaby, Sarah; Petrara, MARIA RAFFAELLA; Burra, Patrizia; Zanus, Giacomo; Zanini, Stefano; Rigotti, Paolo; Maria, Rendina; Alfredodi, Leo; Francesco Paolo Schena, ; Giuseppe, Grandaliano; Marco, Fiorentino; Augusto, Lauro; Antonio Daniele Pinna, ; Paolodi, Gioia; Sara, Pellegrini; Chiara, Zanfi; Maria Piera Scolari, ; Sergio, Stefoni; Paolatodeschini, ; Laura, Panicali; Chiara, Valentini; Umberto, Baccarani; Andrea, Risaliti; Gian Luigi Adani, ; Dario, Lorenzin; Giuseppe Maria Ettorre, ; Giovanni, Vennarecci; Marco, Colasanti; Manuela, Coco; Fabrizio, Ettorre; Roberto, Santoro; Luciamiglioresi, ; Francesco, Nudo; Massimo, Rossi; Gianluca, Mennini; Luca, Toti; Giuseppetisone, ; Annachiara, Casella; Laura, Fazzolari; Daniele, Sforza; Giuseppe, Iaria; Carlo, Gazia; Chiara, Belardi; Claudiacimaglia, ; Alessandro, Agresta; Gianpiero, D’Offizi; Ubaldo Visco Comandini, ; Raffaella, Lionetti; Marzia, Montalbano; Chiara, Taibi; Giovanni, Fantola; Fausto, Zamboni; Gian Benedetto Piredda, ; Maria Benigna Michittu, ; Maria Gavina Murgia, ; Bruno, Onano; Lucia, Fratino; Luigino Dal Maso, ; Paolo De Paoli, ; Diana, Verdirosi; Emanuela, Vaccher; Francesco, Pisani; Antonio, Famulari; Federica, Delreno; Samuele, Iesari; Lindade, Luca; Maurizio, Iaria; Enzo, Capocasale; Elena, Cremaschi; Silvio, Sandrini; Francesca, Valerio; Valentina, Mazzucotelli; Nicola, Bossini; Gisella, Setti; Massimiliano, Veroux; Pierfrancesco, Veroux; Giuseppe, Giuffrida; Alessia, Giaquinta; Domenico, Zerbo; Ghilbusnach, ; Laura Di Leo, ; Maria Luisa Perrino, ; Marialuisa, Querques; Valerianacolombo, ; Maria Chiara Sghirlanzoni, ; Piergiorgio, Messa; Antonio, Leoni; Laura, Galatioto; Salvatore, Gruttadauria; Vito, Sparacino; Flaviacaputo, ; Barbara, Buscemi; Franco, Cit-terio; Gionata, Spagnoletti; Maria Paola Salerno, ; Evaldo Favi Giuseppe Paolo Segoloni, ; Luigi, Biancone; Antoniolavacca, ; Maria Cristina Maresca, ; Carmelocascone, ; Bice, Virgilio; Donato, Donati; Fiorella, Dossi; Andrea, Fontanella; Andrea, Ambrosini; Marco Di Cicco

    Efficacy of acute administration of inhaled argon on traumatic brain injury in mice

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    BACKGROUND: Whilst there has been progress in supportive treatment for traumatic brain injury (TBI), specific neuroprotective interventions are lacking. Models of ischaemic heart and brain injury show the therapeutic potential of argon gas, but it is still not known whether inhaled argon (iAr) is protective in TBI. We tested the effects of acute administration of iAr on brain oedema, tissue micro-environmental changes, neurological functions, and structural outcome in a mouse model of TBI. METHODS: Anaesthetised adult C57BL/6J mice were subjected to severe TBI by controlled cortical impact. Ten minutes after TBI, the mice were randomised to 24 h treatments with iAr 70%/O2 30% or air (iCtr). Sensorimotor deficits were evaluated up to 6 weeks post-TBI by three independent tests. Cognitive function was evaluated by Barnes maze test at 4 weeks. MRI was done to examine brain oedema at 3 days and white matter damage at 5 weeks. Microglia/macrophages activation and functional commitment were evaluated at 1 week after TBI by immunohistochemistry. RESULTS: iAr significantly accelerated sensorimotor recovery and improved cognitive deficits 1 month after TBI, with less white matter damage in the ipsilateral fimbria and body of the corpus callosum. Early changes underpinning protection included a reduction of pericontusional vasogenic oedema and of the inflammatory response. iAr significantly reduced microglial activation with increases in ramified cells and the M2-like marker YM1. CONCLUSIONS: iAr accelerates recovery of sensorimotor function and improves cognitive and structural outcome 1 month after severe TBI in adult mice. Early effects include a reduction of brain oedema and neuroinflammation in the contused tissue

    Accuracy of intracranial pressure monitoring : systematic review and meta-analysis

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    Introduction: Intracranial pressure (ICP) measurement is used to tailor interventions and to assist in formulating the prognosis for traumatic brain injury patients. Accurate data are therefore essential. The aim of this study was to verify the accuracy of ICP monitoring systems on the basis of a literature review. Methods: A PubMed search was conducted from 1982 to 2014, plus additional references from the selected papers. Accuracy was defined as the degree of correspondence between the pressure read by the catheter and a reference "real" ICP measurement. Studies comparing simultaneous readings from at least two catheters were included. Drift was defined as the loss of accuracy over the monitoring period. Meta-analyses of data from the studies were used to estimate the overall mean difference between simultaneous ICP measurements and their variability. Individual studies were weighted using both a fixed and a random effects model. Results: Of 163 articles screened, 83 compared two intracranial catheters: 64 reported accuracy and 37 drift(some reported both). Of these, 10 and 17, respectively, fulfilled the inclusion criteria for accuracy and zero drift analysis. The combined mean differences between probes were 1.5mmHg (95% confidence interval (CI) 0.7-2.3) with the random effects model and 1.6mmHg (95% CI 1.3-1.9) with the fixed effects model. The reported mean drift over a long observation period was 0.75mmHg. No relation was found with the duration of monitoring or differences between various probes. Conclusions: This study confirms that the average error between ICP measures is clinically negligible. The random effects model, however, indicates that a high percentage of readings may vary over a wide range, with clinical implications both for future comparison studies and for daily care

    Label-free monitoring of tissue biochemistry following traumatic brain injury using Raman spectroscopy.

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    Traumatic brain injury (TBI) constitutes a major cause of death and long-term disability. At present, we lack methods to non-invasively track tissue biochemistry and hence select appropriate interventions for patients. We hypothesized that detailed label-free vibrational chemical analysis of focal TBI could provide such information. We assessed the early spatial and temporal changes in tissue biochemistry that are associated with brain injury in mice. Numerous differences were observed in the spectra of the contusion core and pericontusional tissue between 2 and 7 days. For example, a strong signal from haem was seen in the contusion core at 2 days due to haemorrhage, which subsequently resolved. More importantly, elevated cholesterol levels were demonstrated by 7 days, which may be a marker of important cell repair processes. Principal component analysis revealed an early 'acute' component dominated by haemorrhage and a delayed component reflecting changes in protein and lipid composition. Notably we demonstrated changes in Raman signature with time even in the contralateral hemisphere when compared to sham control mice. Raman spectroscopy therefore shows promise as a probe that is sensitive to important pathobiological processes in TBI and could be applied in future both in the experimental setting, as well as in the clinic

    Mineralogical evolution of cement pastes at early ages based on thermogravimetric analysis (TGA)

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    [EN] Ordinary thermogravimetric analysis (TG) and high-resolution TG tests were carried out on three different Portland cement pastes to study the phases present during the first day of hydration. Tests were run at 1, 6, 12 and 24 h of hydration, in order to determine the phases at these ages. High-resolution TG tests were used to separate decompositions presented in the 100¿200 C interval. The non-evaporable water determined by TG was used to determine hydration degree for the different ages. The effect of particle size distribution (PSD) on mineralogical evolution was established, as well as the addition of calcite as mineralogical filler. Finer PSD and calcite addition accelerate the hydration process, increasing the hydration degree on the first day of eaction between water and cement. According to high-resolution TG results, it was demonstrated that ettringite was the only decomposed phase in the 100¿200 C interval during the first 6 h of hydration for all studied cements. 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Capillary pressure in fresh cement-based materials and identification of the air entry value. Cem Concr Compos. 2008;30(7):557–65.Evju C, Hansen S. Expansive properties of ettringite in a mixture of calcium aluminate cement, Portland cement and ß-calcium sulfate hemihydrates. Cem Concr Res. 2001;31:257–61.Bentz DP, Jensen OM, Hansen KK. Olesen, Stang, H. Haecker, C.J. Influence of cement particle-size distribution on early age autogenous strain and stresses in cement-based materials. J Am Ceram Soc. 2001;84(1):129–35.Barcelo L, Moranville M, Clavaud B. Autogenous shrinkage of concrete: a balance between autogenous swelling and self-desiccation. Cem Concr Res. 2005;35(1):177–83.Bouasker M, Mounanga P, Turcry P, Loukili A, Khelidj A. Chemical shrinkage of cement pastes and mortars at very early age: effect of limestone filler and granular inclusions. Cem Concr Compos. 2008;30(1):13–22.Bentz DP. A review of early-age properties of cement-based materials. 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    Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53

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    The p53 pro-apoptotic tumor suppressor is mutated or functionally altered in most cancers. In epithelial tumors induced by “high-risk” mucosal Human Papillomaviruses (hrm-HPVs), including human cervical carcinoma and a growing number of head-and-neck cancers (1), p53 is degraded by the viral oncoprotein E6 (2). In this process, E6 binds to a short LxxLL consensus sequence within the cellular ubiquitin ligase E6AP (3). Subsequently, the E6/E6AP heterodimer recruits and degrades p53 (4). Neither E6 nor E6AP are separately able to recruit p53 (3,5), and the precise mode of assembly of E6, E6AP and p53 is unknown. Here, we solved the crystal structure of a ternary complex comprising full-length HPV16 E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumor suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against HPV-mediated oncogenesis
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