Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

A neural tracking and motor control approach to improve rehabilitation of upper limb movements

<p>Abstract</p> <p>Background</p> <p>Restoration of upper limb movements in subjects recovering from stroke is an essential keystone in rehabilitative practices. Rehabilitation of arm movements, in fact, is usually a far more difficult one as compared to that of lower extremities. For these reasons, researchers are developing new methods and technologies so that the rehabilitative process could be more accurate, rapid and easily accepted by the patient. This paper introduces the proof of concept for a new non-invasive FES-assisted rehabilitation system for the upper limb, called smartFES (sFES), where the electrical stimulation is controlled by a biologically inspired neural inverse dynamics model, fed by the kinematic information associated with the execution of a planar goal-oriented movement. More specifically, this work details two steps of the proposed system: an <it>ad hoc </it>markerless motion analysis algorithm for the estimation of kinematics, and a neural controller that drives a synthetic arm. The vision of the entire system is to acquire kinematics from the analysis of video sequences during planar arm movements and to use it together with a neural inverse dynamics model able to provide the patient with the electrical stimulation patterns needed to perform the movement with the assisted limb.</p> <p>Methods</p> <p>The markerless motion tracking system aims at localizing and monitoring the arm movement by tracking its silhouette. It uses a specifically designed motion estimation method, that we named Neural Snakes, which predicts the arm contour deformation as a first step for a silhouette extraction algorithm. The starting and ending points of the arm movement feed an Artificial Neural Controller, enclosing the muscular Hill's model, which solves the inverse dynamics to obtain the FES patterns needed to move a simulated arm from the starting point to the desired point. Both position error with respect to the requested arm trajectory and comparison between curvature factors have been calculated in order to determine the accuracy of the system.</p> <p>Results</p> <p>The proposed method has been tested on real data acquired during the execution of planar goal-oriented arm movements. Main results concern the capability of the system to accurately recreate the movement task by providing a synthetic arm model with the stimulation patterns estimated by the inverse dynamics model. In the simulation of movements with a length of ± 20 cm, the model has shown an unbiased angular error, and a mean (absolute) position error of about 1.5 cm, thus confirming the ability of the system to reliably drive the model to the desired targets. Moreover, the curvature factors of the factual human movements and of the reconstructed ones are similar, thus encouraging future developments of the system in terms of reproducibility of the desired movements.</p> <p>Conclusion</p> <p>A novel FES-assisted rehabilitation system for the upper limb is presented and two parts of it have been designed and tested. The system includes a markerless motion estimation algorithm, and a biologically inspired neural controller that drives a biomechanical arm model and provides the stimulation patterns that, in a future development, could be used to drive a smart Functional Electrical Stimulation system (sFES). The system is envisioned to help in the rehabilitation of post stroke hemiparetic patients, by assisting the movement of the paretic upper limb, once trained with a set of movements performed by the therapist or in virtual reality. Future work will include the application and testing of the stimulation patterns in real conditions.</p

Analysis of the Lung Microbiome in the “Healthy” Smoker and in COPD

Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD). We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation. We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS). Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups. Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients. The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects. Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups. No genera were common within a group but unique across groups. Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas. Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD. These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients

TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis

Abstract Background We have shown previously that murine gammaherpesvirus 68 (γHV68) infection exacerbates established pulmonary fibrosis. Because Toll-like receptor (TLR)-9 may be important in controlling the immune response to γHV68 infection, we examined how TLR-9 signaling effects exacerbation of fibrosis in response to viral infection, using models of bleomycin- and fluorescein isothiocyanate-induced pulmonary fibrosis in wild-type (Balb/c) and TLR-9-/- mice. Results We found that in the absence of TLR-9 signaling, there was a significant increase in collagen deposition following viral exacerbation of fibrosis. This was not associated with increased viral load in TLR-9-/- mice or with major alterations in T helper (Th)1 and Th2 cytokines. We examined alveolar epithelial-cell apoptosis in both strains, but this could not explain the altered fibrotic outcomes. As expected, TLR-9-/- mice had a defect in the production of interferon (IFN)-β after viral infection. Balb/c fibroblasts infected with γHV68 in vitro produced more IFN-β than did infected TLR-9-/- fibroblasts. Accordingly, in vitro infection of Balb/c fibroblasts resulted in reduced proliferation rates whereas infection of TLR-9-/- fibroblasts did not. Finally, therapeutic administration of CpG oligodeoxynucleotides ameliorated bleomycin-induced fibrosis in wild-type mice. Conclusions These results show a protective role for TLR-9 signaling in murine models of lung fibrosis, and highlight differences in the biology of TLR-9 between mice and humans.http://deepblue.lib.umich.edu/bitstream/2027.42/112877/1/13069_2011_Article_57.pd

Cross-Dimensional Mapping of Number, Length and Brightness by Preschool Children

Human adults in diverse cultures, children, infants, and non-human primates relate number to space, but it is not clear whether this ability reflects a specific and privileged number-space mapping. To investigate this possibility, we tested preschool children in matching tasks where the dimensions of number and length were mapped both to one another and to a third dimension, brightness. Children detected variation on all three dimensions, and they reliably performed mappings between number and length, and partially between brightness and length, but not between number and brightness. Moreover, children showed reliably better mapping of number onto the dimension of length than onto the dimension of brightness. These findings suggest that number establishes a privileged mapping with the dimension of length, and that other dimensions, including brightness, can be mapped onto length, although less efficiently. Children's adeptness at number-length mappings suggests that these two dimensions are intuitively related by the end of the preschool years

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Long Lamai community ICT4D E‐commerce system modelling: an agent oriented role‐based approach

This paper presents the post‐mortem report upon completion of the Long Lamai e‐commerce development project. Some weaknesses with regards to the current software modelling approach are identified and an alternative role‐based approach is proposed. We argue that the existing software modelling technique is not suitable for modelling, making it difficult to establish a good contract between stakeholders causing delays in the project delivery. The role‐based approach is able to explicitly highlight the responsibilities among stakeholders, while also forming the contract agreement among them leading towards sustainable ICT4D