Improvement of the inhibitory effect of xanthones on NO production by encapsulation in PLGA nanocapsules

For the first time the inhibitory effect of xanthone and 3-methoxyxanthone on nitric oxide (NO) production by IFN-gamma/LPS activated J774 macrophage cell line is reported. A remarkable improvement of this effect promoted by encapsulation of these compounds in nanocapsules of Poly (DL-lactide-co-glycolide) (PLGA) is also demonstrated. A weak inhibitory effect of 3.6% on NO production by activated macrophages was observed for xanthone at the highest studied concentration (100 mu M). This effect was slightly higher for 3-methoxyxanthone at the same concentration, producing a reduction of 16.5% on NO production. In contrast, equivalent concentrations of xanthone and 3-methoxyxanthone incorporated in nanocapsules produced a significant decrease on NO production of 91.8 and 80.0%, respectively. Empty nanocapsules also exhibited a slight NO inhibitory activity, which may be due to the presence of soybean lecithin in the composition of the nanosystems. The viability of the macrophages was not affected either by free or nanoencapsulated xanthones. Fluorescence microscopy analysis confirmed that a phagocytic process was involved in the macrophage uptake of xanthone- and 3-methoxyxanthone-loaded PLGA nanocapsules. Phagocytosis might be the main mechanism responsible for the enhancement of the intracellular delivery of both compounds and consequently for the improvement of their biological effect

Comparison of the frequency of bacterial and viral infections among children with community-acquired pneumonia hospitalized across distinct severity categories: a prospective cross-sectional study

Background: The comparison of the frequencies of bacterial and viral infections among children with community-acquired pneumonia (CAP) admitted in distinct severity categories, in an original study, is lacking in literature to-date. We aimed to achieve this goal.Methods: Children aged 2-59-months-old hospitalized with CAP were included in this prospective study in Salvador, Brazil. Clinical data and biological samples were collected to investigate 11 viruses and 8 bacteria. Severity was assessed by using the World Health Organization criteria.Results: One hundred eighty-one patients were classified as "non-severe" (n = 53; 29.3 %), "severe" (n = 111; 61.3 %), or "very severe" (n = 17; 9.4 %) CAP. Overall, aetiology was detected among 156 (86.2 %) cases; viral (n = 84; 46.4 %), bacterial (n = 26; 14.4 %) and viral-bacterial (n = 46; 25.4 %) infections were identified. Viral infection frequency was similar in severe/very severe and non-severe cases (46.1 % vs. 47.2 %; p = 0.9). Pneumococcal infection increased across "non-severe" (13.2 %), "severe" (23.4 %), and "very severe" (35.3 %) cases (qui-squared test for trend p = 0.04). Among patients with detected aetiology, after excluding cases with co-infection, the frequency of sole bacterial infection was different (p = 0.04) among the categories; non-severe (12.5 %), severe (29.3 %) or very severe (55.6 %). Among these patients, sole bacterial infection was independently associated with severity (OR = 4.4 [95 % CI:1.1-17. 6]; p = 0.04) in a model controlled for age (OR = 0.7 [95 % CI:0.5-1.1]; p = 0.1).Conclusions: A substantial proportion of cases in distinct severity subgroups had respiratory viral infections, which did not differ between severity categories. Bacterial infection, particularly pneumococcal infection, was more likely among severe/very severe cases

Physical activity and education about physical activity for chronic musculoskeletal pain in children and adolescents

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To evaluate the effectiveness of physical activity or education about physical activity, or both, compared to active medical care, waiting list, or usual care in children and adolescents with chronic musculoskeletal pain.National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS)

Social representations of HIV/AIDS in five Central European and Eastern European countries: A multidimensional analysis

Cognitive processing models of risky sexual behaviour have proliferated in the two decades since the first reporting of HIV/AIDS, but far less attention has been paid to individual and group representations of the epidemic and the relationship between these representations and reported sexual behaviours. In this study, 494 business people and medics from Estonia, Georgia, Hungary, Poland and Russia sorted free associations around HIV/AIDS in a matrix completion task. Exploratory factor and multidimensional scaling analyses revealed two main dimensions (labelled ‘Sex’ and ‘Deadly disease’), with significant cultural and gender variations along both dimension scores. Possible explanations for these results are discussed in the light of growing concerns over the spread of the epidemic in this region

Unsupervised Bayesian linear unmixing of gene expression microarrays

Background: This paper introduces a new constrained model and the corresponding algorithm, called unsupervised Bayesian linear unmixing (uBLU), to identify biological signatures from high dimensional assays like gene expression microarrays. The basis for uBLU is a Bayesian model for the data samples which are represented as an additive mixture of random positive gene signatures, called factors, with random positive mixing coefficients, called factor scores, that specify the relative contribution of each signature to a specific sample. The particularity of the proposed method is that uBLU constrains the factor loadings to be non-negative and the factor scores to be probability distributions over the factors. Furthermore, it also provides estimates of the number of factors. A Gibbs sampling strategy is adopted here to generate random samples according to the posterior distribution of the factors, factor scores, and number of factors. These samples are then used to estimate all the unknown parameters. Results: Firstly, the proposed uBLU method is applied to several simulated datasets with known ground truth and compared with previous factor decomposition methods, such as principal component analysis (PCA), non negative matrix factorization (NMF), Bayesian factor regression modeling (BFRM), and the gradient-based algorithm for general matrix factorization (GB-GMF). Secondly, we illustrate the application of uBLU on a real time-evolving gene expression dataset from a recent viral challenge study in which individuals have been inoculated with influenza A/H3N2/Wisconsin. We show that the uBLU method significantly outperforms the other methods on the simulated and real data sets considered here. Conclusions: The results obtained on synthetic and real data illustrate the accuracy of the proposed uBLU method when compared to other factor decomposition methods from the literature (PCA, NMF, BFRM, and GB-GMF). The uBLU method identifies an inflammatory component closely associated with clinical symptom scores collected during the study. Using a constrained model allows recovery of all the inflammatory genes in a single factor

Synthesis and Anti-Mycobacterium tuberculosis Activity of Imidazo[2,1-b][1,3]oxazine Derivatives against Multidrug-Resistant Strains

The emergence of multidrug-resistant strains of M. tuberculosis has raised concerns due to the greater difficulties in patient treatment and higher mortality rates. Herein, we revisited the 2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine scaffold and identified potent new carbamate derivatives having MIC90 values of 0.18–1.63 μM against Mtb H37Rv. Compounds 47–49, 51–53, and 55 exhibited remarkable activity against a panel of clinical isolates, displaying MIC90 values below 0.5 μM. In Mtb-infected macrophages, several compounds demonstrated a 1-log greater reduction in mycobacterial burden than rifampicin and pretomanid. The compounds tested did not exhibit significant cytotoxicity against three cell lines or any toxicity to Galleria mellonella. Furthermore, the imidazo[2,1-b][1,3]oxazine derivatives did not show substantial activity against other bacteria or fungi. Finally, molecular docking studies revealed that the new compounds could interact with the deazaflavin-dependent nitroreductase (Ddn) in a similar manner to pretomanid. Collectively, our findings highlight the chemical universe of imidazo[2,1-b][1,3]oxazines and their promising potential against MDR-TB

Fast, scalable, Bayesian spike identification for multi-electrode arrays

We present an algorithm to identify individual neural spikes observed on high-density multi-electrode arrays (MEAs). Our method can distinguish large numbers of distinct neural units, even when spikes overlap, and accounts for intrinsic variability of spikes from each unit. As MEAs grow larger, it is important to find spike-identification methods that are scalable, that is, the computational cost of spike fitting should scale well with the number of units observed. Our algorithm accomplishes this goal, and is fast, because it exploits the spatial locality of each unit and the basic biophysics of extracellular signal propagation. Human intervention is minimized and streamlined via a graphical interface. We illustrate our method on data from a mammalian retina preparation and document its performance on simulated data consisting of spikes added to experimentally measured background noise. The algorithm is highly accurate

Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways

Background: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host. Methodology/Principal Findings: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior. Conclusions: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context

Genetic characterization of morphologically variant strains of Paracoccidioides brasiliensis

Molecular characterization of Paracoccidioides brasiliensis variant strains that had been preserved under mineral oil for decades was carried out by random amplified polymorphic DNA analysis (RAPD). On P. brasiliensis variants in the transitional phase and strains with typical morphology, RAPD produced reproducible polymorphic amplification products that differentiated them. A dendrogram based on the generated RAPD patterns placed the 14 P. brasiliensis strains into five groups with similarity coefficients of 72%. A high correlation between the genotypic and phenotypic characteristics of the strains was observed. A 750 bp-RAPD fragment found only in the wild-type phenotype strains was cloned and sequenced. Genetic similarity analysis using BLASTx suggested that this RAPD marker represents a putative domain of a hypothetical flavin-binding monooxygenase (FMO)-like protein of Neurospora crassa.FiocruzBritish Council Progra