Clinical identification of feeding and swallowing disorders in 0-6 month old infants with Down syndrome

Feeding and swallowing disorders have been described in children with a variety of neurodevelopmental disabilities, including Down syndrome (DS). Abnormal feeding and swallowing can be associated with serious sequelae such as failure to thrive and respiratory complications, including aspiration pneumonia. Incidence of dysphagia in young infants with DS has not previously been reported. To assess the identification and incidence of feeding and swallowing problems in young infants with DS, a retrospective chart review of 174 infants, ages 0-6 months was conducted at a single specialty clinic. Fifty-seven percent (100/174) of infants had clinical concerns for feeding and swallowing disorders that warranted referral for Videofluroscopic Swallow Study (VFSS); 96/174 (55%) had some degree of oral and/or pharyngeal phase dysphagia and 69/174 (39%) had dysphagia severe enough to warrant recommendation for alteration of breast milk/formula consistency or nonoral feeds. Infants with certain comorbidities had significant risk for significant dysphagia, including those with functional airway/respiratory abnormalities (OR = 7.2). Infants with desaturation with feeds were at dramatically increased risk (OR = 15.8). All young infants with DS should be screened clinically for feeding and swallowing concerns. If concerns are identified, consideration should be given to further evaluation with VFSS for identification of dysphagia and additional feeding modifications

Study of the Germination Dynamics for Plants using Advanced Image Processing Algorithms

Study of the Germination Dynamics for Plants using Advanced Image Processing Algorithm

GPs are from Mars, Administrators are from Venus: The Role of Misaligned Occupational Dispositions in Inhibiting Mandated Role Change

Research on mandated occupational role change focuses on jurisdictional conflict to explain change failure. Our study of the English National Health Service highlights the role of occupational dispositions in shaping how mandated role change is implemented by members of multiple occupational groups. We find that tension stemming from misaligned dispositions may emerge as members of different occupations interact during their role change implementation efforts. Depending on dispositional responses to tension, change may fail as members of the different occupations avoid interactions. This suggests that effective role change can be elusive even in the initial absence of conflicting occupational interests

An improved, high-quality draft genome sequence of the Germination-Arrest Factor-producing Pseudomonas fluorescens WH6

<p>Abstract</p> <p>Background</p> <p><it>Pseudomonas fluorescens </it>is a genetically and physiologically diverse species of bacteria present in many habitats and in association with plants. This species of bacteria produces a large array of secondary metabolites with potential as natural products. <it>P. fluorescens </it>isolate WH6 produces Germination-Arrest Factor (GAF), a predicted small peptide or amino acid analog with herbicidal activity that specifically inhibits germination of seeds of graminaceous species.</p> <p>Results</p> <p>We used a hybrid next-generation sequencing approach to develop a high-quality draft genome sequence for <it>P. fluorescens </it>WH6. We employed automated, manual, and experimental methods to further improve the draft genome sequence. From this assembly of 6.27 megabases, we predicted 5876 genes, of which 3115 were core to <it>P. fluorescens </it>and 1567 were unique to WH6. Comparative genomic studies of WH6 revealed high similarity in synteny and orthology of genes with <it>P. fluorescens </it>SBW25. A phylogenomic study also placed WH6 in the same lineage as SBW25. In a previous non-saturating mutagenesis screen we identified two genes necessary for GAF activity in WH6. Mapping of their flanking sequences revealed genes that encode a candidate anti-sigma factor and an aminotransferase. Finally, we discovered several candidate virulence and host-association mechanisms, one of which appears to be a complete type III secretion system.</p> <p>Conclusions</p> <p>The improved high-quality draft genome sequence of WH6 contributes towards resolving the <it>P. fluorescens </it>species, providing additional impetus for establishing two separate lineages in <it>P. fluorescens</it>. Despite the high levels of orthology and synteny to SBW25, WH6 still had a substantial number of unique genes and represents another source for the discovery of genes with implications in affecting plant growth and health. Two genes are demonstrably necessary for GAF and further characterization of their proteins is important for developing natural products as control measure against grassy weeds. Finally, WH6 is the first isolate of <it>P. fluorescens </it>reported to encode a complete T3SS. This gives us the opportunity to explore the role of what has traditionally been thought of as a virulence mechanism for non-pathogenic interactions with plants.</p

Antigen-specific immune responses to influenza vaccine in utero

Initial immune responses to allergens may occur before birth, thereby modulating the subsequent development of atopy. This paradigm remains controversial, however, due to the inability to identify antigen-specific T cells in cord blood. The advent of MHC tetramers has revolutionized the detection of antigen-specific T cells. Tetramer staining of cord blood after CMV infection has demonstrated that effective CD8+ antigen-specific immune responses can follow intrauterine viral infections. We hypothesized that sensitization to antigens occurs in utero in humans. We studied cord blood B and T cell immune responses following vaccination against influenza during pregnancy. Anti-Fluzone and anti-matrix protein IgM antibodies were detected in 38.5% (27 of 70) and 40.0% (28 of 70), respectively, of cord blood specimens. Using MHC tetramers, HA-specific CD4+ T cells were detected among 25.0% (3 of 12) and 42.9% (6 of 14) of cord blood specimens possessing DRB1*0101 and DRB1*0401 HLA types, respectively, and were detected even when the DRB1 HLA type was inherited from the father. Matrix protein–specific CD8+ T cells were detected among 10.0% (2 of 20) of HLA-A*0201+ newborns. These results suggest that B and T cell immune responses occur in the fetus following vaccination against influenza and have important implications for determining when immune responses to environmental exposures begin

Expression profile of human Fc receptors in mucosal tissue: implications for antibody-dependent cellular effector functions targeting HIV-1 transmission

The majority of new Human Immunodeficiency Virus (HIV)-1 infections are acquired via sexual transmission at mucosal surfaces. Partial efficacy (31.2%) of the Thai RV144 HIV-1 vaccine trial has been correlated with Antibody-dependent Cellular Cytotoxicity (ADCC) mediated by non-neutralizing antibodies targeting the V1V2 region of the HIV-1 envelope. This has led to speculation that ADCC and other antibody-dependent cellular effector functions might provide an important defense against mucosal acquisition of HIV-1 infection. However, the ability of antibody-dependent cellular effector mechanisms to impact on early mucosal transmission events will depend on a variety of parameters including effector cell type, frequency, the class of Fc-Receptor (FcR) expressed, the number of FcR per cell and the glycoslyation pattern of the induced antibodies. In this study, we characterize and compare the frequency and phenotype of IgG (CD16 [FcγRIII], CD32 [FcγRII] and CD64 [FcγRI]) and IgA (CD89 [FcαR]) receptor expression on effector cells within male and female genital mucosal tissue, colorectal tissue and red blood cell-lysed whole blood. The frequency of FcR expression on CD14+ monocytic cells, myeloid dendritic cells and natural killer cells were similar across the three mucosal tissue compartments, but significantly lower when compared to the FcR expression profile of effector cells isolated from whole blood, with many cells negative for all FcRs. Of the three tissues tested, penile tissue had the highest percentage of FcR positive effector cells. Immunofluorescent staining was used to determine the location of CD14+, CD11c+ and CD56+ cells within the three mucosal tissues. We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria. The potential implication of the observed FcR expression patterns on the effectiveness of FcR-dependent cellular effector functions to impact on the initial events in mucosal transmission and dissemination warrants further mechanistic studies

Connecting Network Properties of Rapidly Disseminating Epizoonotics

To effectively control the geographical dissemination of infectious diseases, their properties need to be determined. To test that rapid microbial dispersal requires not only susceptible hosts but also a pre-existing, connecting network, we explored constructs meant to reveal the network properties associated with disease spread, which included the road structure.Using geo-temporal data collected from epizoonotics in which all hosts were susceptible (mammals infected by Foot-and-mouth disease virus, Uruguay, 2001; birds infected by Avian Influenza virus H5N1, Nigeria, 2006), two models were compared: 1) 'connectivity', a model that integrated bio-physical concepts (the agent's transmission cycle, road topology) into indicators designed to measure networks ('nodes' or infected sites with short- and long-range links), and 2) 'contacts', which focused on infected individuals but did not assess connectivity.THE CONNECTIVITY MODEL SHOWED FIVE NETWORK PROPERTIES: 1) spatial aggregation of cases (disease clusters), 2) links among similar 'nodes' (assortativity), 3) simultaneous activation of similar nodes (synchronicity), 4) disease flows moving from highly to poorly connected nodes (directionality), and 5) a few nodes accounting for most cases (a "20:80" pattern). In both epizoonotics, 1) not all primary cases were connected but at least one primary case was connected, 2) highly connected, small areas (nodes) accounted for most cases, 3) several classes of nodes were distinguished, and 4) the contact model, which assumed all primary cases were identical, captured half the number of cases identified by the connectivity model. When assessed together, the synchronicity and directionality properties explained when and where an infectious disease spreads.Geo-temporal constructs of Network Theory's nodes and links were retrospectively validated in rapidly disseminating infectious diseases. They distinguished classes of cases, nodes, and networks, generating information usable to revise theory and optimize control measures. Prospective studies that consider pre-outbreak predictors, such as connecting networks, are recommended

A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6–24 hours), neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days), they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours). The process is further enhanced by elevating the production of the chemoattractant SDf-1α and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies

High-Throughput Sequencing of Arabidopsis microRNAs: Evidence for Frequent Birth and Death of MIRNA Genes

In plants, microRNAs (miRNAs) comprise one of two classes of small RNAs that function primarily as negative regulators at the posttranscriptional level. Several MIRNA genes in the plant kingdom are ancient, with conservation extending between angiosperms and the mosses, whereas many others are more recently evolved. Here, we use deep sequencing and computational methods to identify, profile and analyze non-conserved MIRNA genes in Arabidopsis thaliana. 48 non-conserved MIRNA families, nearly all of which were represented by single genes, were identified. Sequence similarity analyses of miRNA precursor foldback arms revealed evidence for recent evolutionary origin of 16 MIRNA loci through inverted duplication events from protein-coding gene sequences. Interestingly, these recently evolved MIRNA genes have taken distinct paths. Whereas some non-conserved miRNAs interact with and regulate target transcripts from gene families that donated parental sequences, others have drifted to the point of non-interaction with parental gene family transcripts. Some young MIRNA loci clearly originated from one gene family but form miRNAs that target transcripts in another family. We suggest that MIRNA genes are undergoing relatively frequent birth and death, with only a subset being stabilized by integration into regulatory networks