Genetic modifiers of Duchenne muscular dystrophy and dilated cardiomyopathy

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. RESULTS: Patients were followed up to an average age of 15.9 \ub1 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). CONCLUSIONS: We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts

Conservation of energy and momenta in nonholonomic systems with affine constraints

We characterize the conditions for the conservation of the energy and of the components of the momentum maps of lifted actions, and of their `gauge-like' generalizations, in time-independent nonholonomic mechanical systems with affine constraints. These conditions involve geometrical and mechanical properties of the system, and are codified in the so-called reaction-annihilator distribution

Resíduos de mancozebe e etu em mamão: efeito do tratamento hidrotérmico pós-colheita.

O mancozebe é um fungicida não sistêmico, e seus resíduos devem ser diferentes em frutos que recebam ou não o tratamento hidrotérmico, por sua remoção da superfície dos frutos. Por outro lado uma das preocupações quanto à sua toxicologia é a formação de um produto de transformação, favorecido pela temperatura, a etilenotiouréia (ETU). A ETU é estável em água e é rapidamente absorvida e metabolizada pelas plantas mas, não é estável quando exposta a matrizes de produtos agrícolas. Os seus resíduos são estabelecidos em 50 µg kg-1 (50ppb) pela União Européia. O objetivo deste trabalho foi avaliar o efeito do tratamento hidrotérmico nos resíduos de mancozebe e de ETU em mamão após aplicações sucessivas de mancozebe

Microarray analyses to identify differentially expressed genes for assessing meat quality in swine

In order to identify candidate genes and molecular mechanisms that influence meat quality and production in pigs, microarray experiments were carried out to find differences in gene expression levels between two pools of six individuals, constituting the extreme tails of the Gaussian distribution of seven adjusted phenotypes of 100 Landrace and Large White animals. The phenotypes considered in this study were: muscle compactness, marbling, colour uniformity, fat covering, colour, dorsal fat, thickness, ham fat thickness. 437 differentially expressed ESTs (Expressed Sequence Tags) were found, clustering in different pathways according to their ontology. In particular, 73 functional categories were identified and ten of them could have a role in meat quality. Among the ESTs belonging to these pathways, seven of them were selected to be validated in quantitative real-time RT-PCR

Prognostic factors and primary healing on root perforation repaired with MTA: a 14-year longitudinal study

Introduction Few data are available on the long-term efficacy of mineral trioxide aggregate (MTA) in treating root canal perforations. This prospective cohort study builds on a previously reported trial to determine the outcome for teeth with root perforations treated with orthograde MTA after longer follow-up and identify potential prognostic factors. Methods A prospective cohort study was performed, enrolling (1999-2009) patients with a single dental perforation treated with MTA. Preoperative, intra-operative, and postoperative information was evaluated, and the outcomes were dichotomized as healed or non-healing. Patients were followed-up yearly until 2018 for a maximum of 17 years post-treatment, with controls carried out until 14 years. Clinical and radiographic outcomes were evaluated using standardized follow-up protocols. Results Of the 124 enrolled patients (median age 36.5 years, 53.2% male), 115 were healed at the first (n=110, 89%) or second (n=5, 4%) annual post-treatment check-up, while 9 subjects (7%, 4 females 18 - 65 YO) did not heal. Characteristics significantly associated with non-healing were gender, positive probing, size, and perforation site. Perforations recurred in 48 teeth during the follow-up with the estimated probability of reversal at 5, 10 and 14 years of 6% (95% CI, 2-10%), 30% (95%CI, 20-38%) and 62% (95% CI,46-73%), respectively. Positive probing had a higher reversal risk (HR=3.3, p≤0.001), and perforations &gt;3mm were more likely to have a reversal (HR=4.1, p&lt;0.001). Conclusions The risk of reversal for healed MTA-treated root canal perforations, initially relatively low, vastly increases over time

Effects of A -site ordering on the Mn local structure and polar phases of R Ba Mn 2 O 6 ( R = La , Nd, Sm, and Y)

We have investigated the temperature dependence of the Mn local structure in A-site ordered RBaMn2O6 (R = La, Nd, Sm, and Y) perovskites, in parallel with their disordered counterparts, R0.5Ba0.5MnO3, by means of x-ray emission (XES) and x-ray absorption spectroscopy (XAS) The end member LaBaMn2O6 shows a nearly regular MnO6 octahedron independent of temperature. With decreasing the R ionic radius in the ordered samples, the XAS results indicate that a local distortion develops in the MnO6 octahedron at the low-temperature charge-localized and polar phases. For NdBaMn2O6, this local distortion is tiny, indicating the absence of charge segregation at the Mn site. This is followed by a bigger local distortion anticipated for SmBaMn2O6 in its respective charge-localized and polar phase and finally, the biggest local distortion for the smallest A-site cation ordered compound, YBaMn2O6, for which it even persists above the polar charge-localization transition temperatures. The high-resolution XAS spectra confirm the presence of charge segregation between two nonequivalent Mn sites in the low-temperature polar phase of Sm and Y ordered samples. Thus, our XAS study suggests a displacive mechanism for the charge-localization and polar transitions in the Nd and Sm ordered samples while a combination of displacive and order-disorder contributions is revealed for YBaMn2O6. Besides, calorimetric measurements confirm the combination of the two mechanisms, order-disorder and displacive, for the ordered Sm and Y compounds. On the other hand, the A-site disordered R0.5Ba0.5MnO3 samples with R cations smaller than Nd present a significant static (temperature-independent) local disorder, which explains why polar charge-localization transitions are not developed in these samples. Finally, we correlate our results about the Mn local structure and character of the transitions with the macroscopic magnetic and electric behavior of both A-site ordered and disordered compounds

Prognostic factors and treatment-effect modifiers in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with Type 1 SMA do not achieve major motor milestones, and death from respiratory failure typically occurs before 2 years. Individuals with Types 2 and 3 SMA exhibit milder phenotypes and have better functional and survival outcomes. Herein, a systematic literature review was conducted to identify factors that influence the prognosis of Types 1, 2 and 3 SMA. In untreated infants with Type 1 SMA, absence of symptoms at birth, a later symptom onset and a higher survival of motor neuron 2 (SMN2) copy number are all associated with increased survival. Disease duration, age at treatment initiation and, to a lesser extent, baseline function were identified as potential treatment-modifying factors for survival, emphasizing that early treatment with disease-modifying therapies (DMT) is essential in Type 1 SMA. In patients with Types 2 and 3 SMA, factors considered prognostic of changes in motor function were SMN2 copy number, age and ambulatory status. Individuals aged 6-15 years were particularly vulnerable to developing complications (scoliosis and progressive joint contractures) which negatively influence functional outcomes and may also affect the therapeutic response in patients. Age at the time of treatment initiation emerged as a treatment-effect modifier on the outcome of DMTs. Factors identified in this review should be considered prior to designing or analyzing studies in an SMA population, conducting population matching or summarizing results from different studies on the treatments for SMA

Towards interoperability in the european poetry community: the standardization of philological concepts

This paper stems from the Poetry Standardization and Linked Open Data project (POSTDATA). As its name reveals, one of the main aims of POSTDATA is to provide a means to publish European poetry (EP) data as Linked Open Data (LOD). Thus, developing a metadata application profile (MAP) as a common semantic model to be used by the EP community is a crucial step of this project. This MAP will enhance interoperability among the community members in particular, and among the EP community and other contexts in general (e.g. bibliographic records). This paper presents the methodology followed in the process of defining the concepts of the domain model of this MAP, as well as some issues that arise when labeling philological terms.info:eu-repo/semantics/publishedVersio