Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial

BACKGROUND Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI

Cognitive performance in healthy older adults relates to spontaneous switching between states of functional connectivity during rest

Growing evidence has shown that brain activity at rest slowly wanders through a repertoire of different states, where whole-brain functional connectivity (FC) temporarily settles into distinct FC patterns. Nevertheless, the functional role of resting-state activity remains unclear. Here, we investigate how the switching behavior of resting-state FC relates with cognitive performance in healthy older adults. We analyse resting-state fMRI data from 98 healthy adults previously categorized as being among the best or among the worst performers in a cohort study of >1000 subjects aged 50+ who underwent neuropsychological assessment. We use a novel approach focusing on the dominant FC pattern captured by the leading eigenvector of dynamic FC matrices. Recurrent FC patterns - or states - are detected and characterized in terms of lifetime, probability of occurrence and switching profiles. We find that poorer cognitive performance is associated with weaker FC temporal similarity together with altered switching between FC states. These results provide new evidence linking the switching dynamics of FC during rest with cognitive performance in later life, reinforcing the functional role of resting-state activity for effective cognitive processing.This project was financed by the Fundação Calouste Gulbenkian (Portugal) (Contract grant number: P-139977; project “Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)”), co-financed by Portuguese North Regional Operational Program (ON.2) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298) and under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement through the European Regional Development Fundinfo:eu-repo/semantics/publishedVersio

The first Galaxy scale hunt for the youngest high-mass protostars

The origin of massive stars is a fundamental open issue in modern astrophysics. Pre-ALMA interferometric studies reveal precursors to early B to late O type stars with collapsing envelopes of 15-20 M$_\odot$ on 1000-3000 AU size-scales. To search for more massive envelopes we selected the most massive nearby young clumps from the ATLASGAL survey to study their protostellar content with ALMA. Our first results using the intermediate scales revealed by the ALMA ACA array providing 3-5" angular resolution, corresponding to $\sim$0.05-0.1 pc size-scales, reveals a sample of compact objects. These massive dense cores are on average two-times more massive than previous studies of similar types of objects. We expect that once the full survey is completed, it will provide a comprehensive view on the origin of the most massive stars

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Relationship between functional fitness, medication costs and mood in elderly people

Objective: to verify if functional fitness (FF) is associated with the annual cost of medication consumption and mood states (MSt) in elderly people. Methods: a cross-sectional study with 229 elderly people aged 65 years or more at Santa Casa de Misericórdia de Coimbra, Portugal. Seniors with physical and psychological limitations were excluded, as well as those using medication that limits performance on the tests. The Senior Fitness Test was used to evaluate FF, and the Profile of Mood States - Short Form to evaluate the MSt. The statistical analysis was based on Mancova, with adjustment for age, for comparison between men and women, and adjustment for sex, for comparison between cardiorespiratory fitness quintiles. The association between the variables under study was made with partial correlation, controlling for the effects of age, sex and body mass index. Results: an inverse correlation between cardiorespiratory fitness and the annual cost of medication consumption was found (p < 0.01). FF is also inversely associated with MSt (p < 0.05). Comparisons between cardiorespiratory fitness quintiles showed higher medication consumption costs in seniors with lower aerobic endurance, as well as higher deterioration in MSt (p < 0.01). Conclusion: elderly people with better FF and, specifically, better cardiorespiratory fitness present lower medication consumption costs and a more positive MSt

Phase behaviour of poly(2, 6-diphenyl-p-phenylene oxide) (PPPO) in mixed solvents

The solution phase behaviour of poly(2, 6-diphenyl-p-phenylene oxide) (PPPO) is investigated by a combination of turbidimetry, infrared spectroscopy, dynamic light scattering and densitometry, combined with calorimetry and X-ray scattering. We select dichloromethane (DCM) and heptane as, respectively, representative good and poor solvents for the polymer. This ternary system results in a miscibility gap which can be utilised for the design and fabrication of PPPO porous materials, membranes and scaffolds via phase inversion. We establish the phase diagram and resolve the kinetic solidification condition arising from the intersection between the coexistence and glass transition curves. PPPO exhibits a high 230 ∘C and is found to crystallise at 336 ∘C, and melt at 423, 445 ∘C with a double endotherm. The kinetics of demixing and (buoyancy-driven) stratification are quantified by optical imaging and the PPPO-rich phase analysed by SAXS/WAXS to resolve both amorphous and crystalline phases. Equipped with this knowledge, we demonstrate the controlled formation of nodular, bicontinuous and cellular morphologies by non-solvent induced demixing

The linked units of 5S rDNA and U1 snDNA of razor shells (Mollusca: Bivalvia: Pharidae)

[Abstract] The linkage between 5S ribosomal DNA and other multigene families has been detected in many eukaryote lineages, but whether it provides any selective advantage remains unclear. In this work, we report the occurrence of linked units of 5S ribosomal DNA (5S rDNA) and U1 small nuclear DNA (U1 snDNA) in 10 razor shell species (Mollusca: Bivalvia: Pharidae) from four different genera. We obtained several clones containing partial or complete repeats of both multigene families in which both types of genes displayed the same orientation. We provide a comprehensive collection of razor shell 5S rDNA clones, both with linked and nonlinked organisation, and the first bivalve U1 snDNA sequences. We predicted the secondary structures and characterised the upstream and downstream conserved elements, including a region at −25 nucleotides from both 5S rDNA and U1 snDNA transcription start sites. The analysis of 5S rDNA showed that some nontranscribed spacers (NTSs) are more closely related to NTSs from other species (and genera) than to NTSs from the species they were retrieved from, suggesting birth-and-death evolution and ancestral polymorphism. Nucleotide conservation within the functional regions suggests the involvement of purifying selection, unequal crossing-overs and gene conversions. Taking into account this and other studies, we discuss the possible mechanisms by which both multigene families could have become linked in the Pharidae lineage. The reason why 5S rDNA is often found linked to other multigene families seems to be the result of stochastic processes within genomes in which its high copy number is determinan

Landscape determinants of European roller foraging habitat: implications for the definition of agri-environmental measures for species conservation

Across much of Europe, farmland birds are declining more than those in other habitats. From a conservation perspective, identifying the primary preferred habitats could help improve the foraging conditions of target species and, consequently, enhance their breeding success and survival. Here, we investigated the ranging behaviour and foraging habitat selection of the European roller (Coracias garrulus) during the breeding season in an agricultural landscape of South Iberia. The occurrence of foraging rollers was predicted to gradually increase with decreasing distance from the nest and increasing availability of perches, such as fences and electric wires. Traditional olive groves and stubble fields were positively and negatively associated with the occurrence of rollers, respectively. Additionally, analysis of hunting strikes showed that rollers highly prefer foraging in fallows rather than cereal or stubble fields. Prey surveys revealed that fallows had the highest abundance of grasshoppers, rollers’ preferred prey during chick-rearing. Pair home-ranges, obtained from 95% fixed Kernel estimators averaged 70.9 ha (range = 34–118 ha) and most foraging trips (80%) occurred in the close vicinity of the nest (<500 m). Number of chicks fledged was not affected by mean foraging distances travelled during the chick-rearing period. Overall, our results suggest that traditional extensive practices of cereal cultivation, with large areas of low-intensity grazed fallows, represent a high-quality foraging habitat for rollers and should be promoted through agri-environmental schemes within at least 1-km radius from the nest. These recommendations are targeted at the roller, but have been shown to apply broadly to several other steppe-bird species

Genetic Variation in the Complete MgPa Operon and Its Repetitive Chromosomal Elements in Clinical Strains of Mycoplasma genitalium

Mycoplasma genitalium has been increasingly recognized as an important microbe not only because of its significant association with human genital tract diseases but also because of its utility as a model for studying the minimum set of genes necessary to sustain life. Despite its small genome, 4.7% of the total genome sequence is devoted to making the MgPa adhesin operon and its nine chromosomal repetitive elements (termed MgPars). The MgPa operon, along with 9 MgPars, is believed to play an important role in pathogenesis of M. genitalium infection and has also served as the main target for development of diagnostic tools. However, genetic variation in the complete MgPa operon and MgPars among clinical strains of M. genitalium has not been addressed. In this study we examined the genetic variation in the complete MgPa operon (approximately 8.5 kb) and full or partial MgPar sequences (0.4–2.6 kb) in 15 geographically diverse strains of M. genitalium. Extensive variation was present in four repeat regions of the MgPa operon (with homology to MgPars) among and within strains while the non-repeat regions (without homology to MgPars) showed low-level variation among strains and no variation within strains. MgPars showed significant variation among strains but were highly homogeneous within strains, supporting gene conversion as the likely recombination mechanism. When applying our sequence data to evaluate published MgPa operon-based diagnostic PCR assays and genotyping systems, we found that 11 of 19 primers contain up to 19 variable nucleotides and that the target for one of two typing systems is located in a hypervariable repeat region, suggesting the likelihood of false results with some of these assays. This study not only provides new insights into the role of the MgPa operon in the pathogenesis of M. genitalium infection but has important implications for the development of diagnostic tools

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)