Silencing mutant ataxin-3 rescues motor deficits and neuropathology in machado-joseph disease transgenic mice.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly-inherited neurodegenerative disorder caused by the over-repetition of a CAG codon in the MJD1 gene. This expansion translates into a polyglutamine tract that confers a toxic gain-of-function to the mutant protein - ataxin-3, leading to neurodegeneration in specific brain regions, with particular severity in the cerebellum. No treatment able to modify the disease progression is available. However, gene silencing by RNA interference has shown promising results. Therefore, in this study we investigated whether lentiviral-mediated allele-specific silencing of the mutant ataxin-3 gene, after disease onset, would rescue the motor behavior deficits and neuropathological features in a severely impaired transgenic mouse model of MJD. For this purpose, we injected lentiviral vectors encoding allele-specific silencing-sequences (shAtx3) into the cerebellum of diseased transgenic mice expressing the targeted C-variant of mutant ataxin-3 present in 70% of MJD patients. This variation permits to discriminate between the wild-type and mutant forms, maintaining the normal function of the wild-type allele and silencing only the mutant form. Quantitative analysis of rotarod performance, footprint and activity patterns revealed significant and robust alleviation of gait, balance (average 3-fold increase of rotarod test time), locomotor and exploratory activity impairments in shAtx3-injected mice, as compared to control ones injected with shGFP. An important improvement of neuropathology was also observed, regarding the number of intranuclear inclusions, calbindin and DARPP-32 immunoreactivity, fluorojade B and Golgi staining and molecular and granular layers thickness. These data demonstrate for the first time the efficacy of gene silencing in blocking the MJD-associated motor-behavior and neuropathological abnormalities after the onset of the disease, supporting the use of this strategy for therapy of MJD

Combined tools for Surgical Case Packages contents and cost optimization: a preliminary study

This paper presents a solution proposal based on mathematical and statistical tools to optimize Surgical Case Packages of an Operating Room (OR) in a Portuguese public hospital that it is the most complex environment in a hospital. In this particular hospital, more than 27000 surgeries/year are performed, employing, sometimes, misadjusted composition of standard surgical packages and non-optimized grouping of surgical instruments. Problem consequences are, among others, high transport of various surgical cases packages; high number of open cases and delays in surgical times following surgery. These type of problems are waste that do not add value to the service in the context of Lean Healthcare and must be eliminated using the most suitable tools. After the analysis, different tools were used: combinatorial analysis to optimize surgical cases composition and statistical analysis to identify the instruments usage and surgical basic case patterns. An optimization model was developed which produced a sterilizing initial solution of 135.24€. By identifying the most commonly employed instruments, it was concluded that some instruments have never been used and others rarely and some patterns were identified. The results achieved were based on minor sample and in a form of data collection that needs some adjustment

Histopathological features of organs in a rat model of mamamry carcinogenesis: a reference database

Mammary tumors’ development was induced through the intraperioneal administration of the carcinogen N-methyl-N-nitrosourea (MNU). Animals from group control were injected with the vehicle (saline solution). Animals were sacrificed at 25 weeks-old and the organs were histopathologically evaluated. A higher number of lesions was observed in the organs of animals from group MNU. The animals from group control did not present any lesion in lymph nodes. Independently of the experimental group, the internal organs presented hemodynamic alterations, degenerative and inflammatory changes. Hemodynamic changes may be consequence of euthanasia method. As expected, the higher number and the higher grade of the lesions in group MNU were due to the carcinogen administration.info:eu-repo/semantics/publishedVersio

Efficacy of adaptive cognitive training through desktop virtual reality and paper-and-pencil in the treatment of mental and behavioral disorders

Cognitive defcits are a core feature of mental and behavioral disorders, leading to poor treatment adherence and functional ity. Virtual reality (VR) methodologies are promising solutions for cognitive interventions in psychiatry once they provide greater ecological validity. This study assessed and compared two content-equivalent cognitive training (CT) interventions, delivered in desktop VR (Reh@City v2.0) and paper-and-pencil (Task Generator (TG)) formats, in patients with mental and behavioral disorders. 30 patients were randomly assigned to the Reh@City v2.0 group and the TG group. Both groups of patients underwent a time-matched 24-sessions intervention. Neuropsychological assessments were performed at baseline, post-intervention, and follow-up. A within-groups analysis revealed signifcant improvements in visual memory and depres sive symptomatology after the Reh@City intervention. The TG group improved in processing speed, verbal memory, and quality of life (social relationships and environmental domains). Between groups, Reh@City led to a greater reduction in depressive symptomatology, whereas the TG group showed higher improvements in social relationships aspects of quality of life. At follow-up, previous gains were maintained and new improvements found in the Reh@City (global cognitive func tion, language, visuospatial and executive functions) and the TG groups (attention). The Reh@City signifcantly reduced depressive symptomatology, and the TG led to greater improvements in processing speed, abstraction, and social relationships domain of quality of life at follow-up. Both interventions were associated with important cognitive, emotional, and quality of life benefts, which were maintained after two months. Reh@City and TG should be considered as complementary CT methods for patients with mental and behavioral disorders. Trial registration The trial is registered at ClinicalTrials.gov, number NCT04291586.info:eu-repo/semantics/publishedVersio

Assessing the diversity of sea beet (Beta vulgaris L. ssp. maritima) populations

Beta vulgaris L. subsp. maritima (L.) Arcang., sea beet, is a morphologically and genetically variable species, belonging to beet primary gene -pool. This crop wild relative is a valuable genetic resource for resistance improvement in beets and could play an important role in crop yield sustainability. Eleven Madeiran sea beet populations were characterized using morphological descriptors and genetic markers. Our goal was to evaluate these populations as a potential source of valuable genetic material. Morphological characterization showed a high quantitative variation among populations. Plant height and inflorescence height parameters had the highest influence in the separation of populations. Molecular analysis was performed with polymorphic SSRs to determine genetic variability between populations. Both PCA and PCoA revealed three clusters that separated the populations according to morphological and genetic traits, respectively. This study contributes to the knowledge of sea beet diversity in Madeira’s archipelago and to the perception that the islands' specific environmental conditions influence its genetic variability, making these populations a possible gene source for sugar beet breeding programsinfo:eu-repo/semantics/publishedVersio

Eficiência de novas bactérias nodulantes em feijão-caupi isoladas de solos do Piauí (1)

O objetivo deste trabalho foi avaliar a capacidade simbiótica de estirpes de BNL em feijão-caupi oriundas de solos do PI, quando cultivado em vasos com amostras de solos contrastantes. O delineamento experimental foi o inteiramente casualizado, com quatro repetições, em esquema fatorial (2 solos x16 tratamentos de inoculação). O experimento foi conduzido no viveiro da Universidade Federal do Piauí, no município de Bom Jesus, utilizando vasos com 4 kg de solo. O cultivar de feijão-caupi utilizado foi a BR 17 Gurguéia. A coleta foi realizada aos 45 dias após a germinação, sendo avaliados o número de nódulo, a matéria fresca e seca dos nódulos, da parte aérea, da raiz e total, eficiência relativa comparando com a testemunha nitrogenada, e acúmulo de nitrogênio na matéria seca da parte aérea. Os insolados UFPI B3-4 e UFPI B5-7A apresentaram capacidade e eficiência na nodulação e na fixação de N2 em feijão-caupi, sendo selecionadas para estudos posteriores em condições de campo

Traditional Calibration Methods in Atomic Spectrometry and New Calibration Strategies for Inductively Coupled Plasma Mass Spectrometry

Applications, advantages, and limitations of the traditional external standard calibration, matrix-matched calibration, internal standardization, and standard additions, as well as the non-traditional interference standard method, standard dilution analysis, multi-isotope calibration, and multispecies calibration methods are discussed

Pyrites in a salt marsh-ria system: quantification, morphology, and mobilization

Galician Rias are among the most productive ecosystems in the world. Consequently, the soils of their salt marshes and sediments of the intertidal flats show high organic matter contents, reactive Fe, and sulfate, which promote pyrite synthesis and accumulation, using sulfate for organic matter decomposition. This work studies the morphological variability and concentration of pyrites (individual crystals and framboids) in different geochemical environments found in the Ria de Ortigueira (salt marsh soils and bottom sediments in the inner, middle, and outer section), addressing their dynamics in the marsh-ria system in relation to the hydrodynamic characteristics defined by tides and river discharges. Framboidal pyrites were the dominant morphology in marsh soils and sediments in the middle and inner sections of the Ria, while isolated crystals dominated its outer section. The results showed that lower marsh soils (colonized by Spartina) are the most favorable environment for pyrite synthesis, showing high pyritic Fe concentrations and high degrees of pyritization, largely exceeding the values observed in sediments from Galician Rias and from most sedimentary environments worldwide. However, the amount of framboidal pyrites present in the lower marsh (SPE: 4–5 × 104 framboids) was clearly lower than in bottom sediments of the inner and middle part of the Ria de Ortigueira (∼2–7 × 106 framboids), mainly due to the fact that pyrites were found to form large framboids in lower salt marsh soils. Thus, the amount of framboidal pyrites does not seem to be a good indicator of redox conditions in modern marine sediments. Pyrite crystals found in the sediments of the Ria showed poorly defined vertices and facets, indicating their degradation and suggesting that a significant amount of the pyrites found in the middle and inner sections derive from marsh collapse. Finally, the output of framboidal pyrites towards the outer Ria de Ortigueira reflects the low intensity of residual flows in this Ria. Therefore, the pyrites observed in the outer section consisted only of isolated crystals, presumably formed in situ under low sulfate-reducing activity conditionsS

Farinha de mandioca de Cruzeiro do Sul: características da identidade regional para a Indicação Geográfica.

Neste capítulo será feito um retorno ao passado para entender como foi a ocupação territorial, a evolução político-administrativa e o início da produção da farinha de mandioca que já era relatada na imprensa desde 1906