Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice

Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD

Indici per la valutazione della qualit? ecologica dei laghi

Collection of methods to evaluate lake quality using biological element

Edición y estudio de la Crónica de San Juan de la Peña, de acuerdo con el manuscrito escurialense N-I.13

La tesis doctoral tiene como objetivo principal ofrecer una edición actualizada de la Crónica de San Juan de la Peña, en su versión en lengua aragonesa, de acuerdo con el manuscrito N-I-13 conservado en la Real Biblioteca del Monasterio de San Lorenzo de El Escorial, copia de finales del siglo XV o principios del XVI de un original perdido de finales del siglo XIV. El códice presenta, al menos, dos singularidades que han despertado nuestro interés y justifican la necesidad de esta investigación: la primera afecta al contenido narrativo de la Crónica, de la cual reproduce la primera refundición, que se llevó a cabo alrededor de la segunda mitad de los años 60 del siglo XIV y que todavía es inédita; la segunda es que el códice transmite una larga traducción en aragonés de la catalana Crónica de Bernat Desclot, interpolada dentro de la narración referente al reinado de Pedro III de Aragón, que revela un proyecto historiográfico alternativo a los oficiales estudiados hasta el momento. El trabajo se divide en dos secciones: la primera de ella contempla el estudio introductorio que comprende tres partes. En la primera se presentan, bajo una nueva perspectiva, los aspectos preliminares acerca de la Crónica de San Juan de la Peña, como el título, la autoría, la datación y las tres fases de redacción de la obra. En la segunda parte del estudio introductorio se hace hincapié en el contexto historiográfico en que se inserta la Crónica, se exponen sus fuentes principales y se detalla el uso de estas en los diferentes capítulos de la obra según el códice editado, analizando también la interpolación de la Crónica de Desclot. Finalmente, en la tercera parte nos ocupamos de cuestiones ecdóticas, presentando la amplia tradición manuscrita de la Crónica y tratando detenidamente del ejemplarescurialense objeto de estudio y su relación con otros códices. La segunda sección de la tesis está dedicada a la edición del texto del manuscrito N-I-13, corregido de sus errores evidentes gracias al cotejo con otros manuscritos y acompañado de un aparato crítico en el cual se registran las lecturas divergentes y/o enmendadas.La presente edición publica por primera vez la segunda versión de la Crónica de San Juan de la Peña y supone, por lo tanto, un avance en el conocimiento del proceso de transmisión y redacción del texto.<br /

El itinerario del Gran Capitán en Nápoles a través de la correspondencia diplomática

El presente Trabajo Final de Máster tiene como objetivo trazar el itinerario militar y político del Gran Capitán, Gonzalo Fernández de Córdoba, en el reino de Nápoles, a través del análisis de la correspondencia diplomática internacional, en el periodo que comprende la segunda campaña napolitana, la experiencia del primer virreinato y los años del regreso definitivo de Gonzalo a España. El propósito es estudiar la figura del Gran Capitán como intermediario de la política expansionista de los Reyes Católicos en el Mediterráneo, sin omitir el análisis de la evolución personal de uno de los personajes más interesantes de los comienzos de la Edad Moderna. El manejo directo de las fuentes ¬¬¬ ¬‒editadas e inéditas‒ ha representado la base de la investigación y ha permitido llegar a un estudio completo del programa político de la recién nacida Monarquía hispánica dentro del complejo panorama italiano de los primeros años del siglo XVI

Muon reconstruction performance of the ATLAS detector in proton–proton collision data at √s = 13 TeV

This article documents the performance of the ATLAS muon identification and reconstruction using the LHC dataset recorded at √s = 13 TeV in 2015. Using a large sample of J/ψ→μμ and Z→μμ decays from 3.2 fb−1 of pp collision data, measurements of the reconstruction efficiency, as well as of the momentum scale and resolution, are presented and compared to Monte Carlo simulations. The reconstruction efficiency is measured to be close to 99% over most of the covered phase space (|η| 2.2, the pT resolution for muons from Z→μμ decays is 2.9 % while the precision of the momentum scale for low-pT muons from J/ψ→μμ decays is about 0.2%

Changes in pharyngeal aerobic microflora in oral breathers after palatal rapid expansion

BACKGROUND: The purpose of this study was to investigate in oral breathing children the qualitative and quantitative effects on aerobic and facultatively anaerobic oropharyngeal microflora of respiratory function improved by rapid palatal expansion (RPE). METHODS: In an open clinical trial, we studied 50 oral breathers, aged 8 to 14 years and suffering from both maxillary constriction and posterior cross-bite. At baseline, patients were examined by a single otorhinolaryngologist (ENT), confirming nasal obstruction in all subjects by posterior rhino-manometric test. Patients were evaluated three times by oropharyngeal swabs:1) at baseline (T = 0); 2) after palatal spreading out (T = 1); and 3) at the end of RPE treatment (T = 2). With regard to the microbiological aspect, the most common and potentially pathogenic oral microrganisms (i.e. Streptococcus pyogenes, Diplococcus pneumoniae, Staphylococcus aureus, Haemophilus spp, Branhamella catarrhalis, Klebsiella pneumoniae, Candida albicans) were specifically detected in proper culture plates, isolated colonies were identified by means of biochemical tests and counted by calibrated loop. The data were analyzed by means of the following tests: Chi-square test, Fisher's exact test and Wilcoxon's test. RESULTS: After the use of RME there was a statistically significant decrease of Staphylococcus aureus stock at CFU/mLat T1(P = 0.0005; Z = -3,455 by Wilcoxon Rank test) and T2 (P < 0.0001; Z = -4,512 by Wilcoxon Rank test) vs T0. No significant changes were found for the other examined microrganisms. CONCLUSION: Our data suggest that RPE therapy in oral breathers may strongly reduce the pathogenic aerobic and facultatively anaerobic microflora in the oral pharynx after a normalization of the upper airways function, and may reduce the risk of respiratory infections

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The Association between Nutritional Alterations and Oral Lesions in a Pediatric Population: An Epidemiological Study

The oral conditions of an individual are the result of different factors, including the subject's genotype, oral hygiene habits, the type of diet, and lifestyle, such as smoking. Nutrition in the first years of life can affect dental health for a long time. To prevent mouth diseases, it is also important to eliminate unfavorable eating behaviour and to amplify protective ones. Eating habits, especially in pediatric age, are an easily modifiable and controllable factor, and diet, in addition to influencing the health of the oral cavity, plays a fundamental role in systemic health. Indeed, a sugar-rich diet can lead to conditions, such as diabetes, being overweight, and obesity. The present research was an epidemiological study, with the aim of highlighting some of the associations between nutrition and oral health. In particular, we studied those lesions of hard and soft tissues that are diagnosed most frequently by dentists: caries, enamel hypoplasia, periodontal disease, and aphotoxic lesions and their associations with nutritional deficiencies and excesses including proteins, vitamin A, vitamin D, B vitamins, and iron and calcium minerals. To perform this study, we recruited 70 patients from the pediatric and orthodontic clinics, aged between 3 and 15 years (y), with mean age of 10.4 y.o. The study was conducted by providing a questionnaire to pediatric patients' (supported from their parents or guardians) on individual eating habits, followed by an accurate oral cavity specialistic examination. The nutritional data were processed by using Grana Padano Observatory (OGP) software, freely provided online by the OPG. The statistical tests performed were the chi-square (χ 2) for independence, and Cramér's V test was used to evaluate the associations between eating habits and oral pathologies. The results showed that certain nutritional vitamin deficiencies and nutritional excesses were associated with definite oral pathologies

The Importance of Mortality Risk Assessment: Validation of the Pediatric Index of Mortality 3 Score

Objective: To evaluate the performance of the newest version of the Pediatric Index of Mortality 3 score and compare it with the Pediatric Index of Mortality 2 in a multicenter national cohort of children admitted to PICU. Design: Retrospective, prospective cohort study. Setting: Seventeen Italian PICUs. Patients: All children 0 to 15 years old admitted in PICU from January 2010 to October 2014. Interventions: None. Measurement and main results: Eleven thousand one hundred nine children were enrolled in the study. The mean Pediatric Index of Mortality 2 and 3 values of 4.9 and 3.9, respectively, differed significantly (p &lt; 0.05). Overall mortality rate was 3.9%, and the standardized mortality ratio was 0.80 for Pediatric Index of Mortality 2 and 0.98 for Pediatric Index of Mortality 3 (p &lt; 0.05). The area under the curve of the receiver operating characteristic curves was similar for Pediatric Index of Mortality 2 and Pediatric Index of Mortality 3. The Hosmer-Lemeshow test was not significant for Pediatric Index of Mortality 3 (p = 0.21) but was highly significant for Pediatric Index of Mortality 2 (p &lt; 0.001), which overestimated death mainly in high-risk categories. Conclusions: Mortality indices require validation in each country where it is used. The new Pediatric Index of Mortality 3 score performed well in an Italian population. Both calibration and discrimination were appropriate, and the score more accurately predicted the mortality risk than Pediatric Index of Mortality 2