siRNA knockdown of SPHK1 in vivo protects mice from systemic, type-I Allergy.

Systemic anaphylaxis is considered to be a typical immediate hypersensitivity response, determined by the activation of immune cells,
via antigen-induced aggregation of IgE-sensitized FcεRI cells. Perhaps most the important cells, in the immediate hypersensitivity responses, are mast cells. We have previously shown that SPHK1 plays a key role in the intracellular signaling pathways triggered by FceRI aggregation on human
mast cells. More recently, we performed a genome-wide gene expression profiling of human mast cells, sensitized with IgE alone, or stimulated by FcεRI aggregation. We found that sphingosine kinase 1 (SPHK1) was one
of genes activated at the earlier stages of mast cell activation, including during sensitization. Moreover, SPHK1 has been shown, by us and others, to be a key player in the intracellular signaling pathways triggered by
several immune-receptors, including fMLP, C5a, and Fcg- and Fcereceptors. Here we have investigated the in vivo role of SPHK1 in allergy, using a specific siRNA to knockdown SPHK1 in vivo. Our results support a role for
SPHK1 in the inflammatory responses that share clinical, immunological, and histological features of type I hypersensitivity. Thus, mice pretreated with the siRNA for SPHK1 were protected from the IgE mediated allergic
reactions including: temperature changes, histamine release, cytokine production, cell-adhesion molecule expression, and immune cell infiltration into the lungs

Differential Gene Expression of Human Mast cell Activation Reveals Gene profiles of Innate and Adaptive Immunity.

High-density oligonucleotide microarray is a promising approach for high throughput analysis. It has been extensively used in many areas of biomedical research. Immunoglobulin E (IgE) mediated allergic response (type-1 hypersensitivity) is one of the most powerful reactions of the immune system. Tissue Mast Cells (MCs) and circulating basophils are the major effector cells in these reactions. By dissecting the regulatory circuitry of mast cells by analyzing the genome wide effects of antigen stimulation triggered by FcεRI, offers a potential for finding novel genes as ‘targets’ for therapeutic intervention. In this work, we tried to study the gene expression pattern in IgE sensitized and FcεRI cross linked cord blood derived MCs using one of the latest techniques, high density oligonucleotide expression probe array (HG-Focus array, Gene Chip, Affymetrix, Santa Clara, CA). Microarray hybridization of RNA from cord blood derived MCs revealed coordinated changes in gene expression in response to IgE stimulation and receptor cross linking at different time points. Among the most prominent findings, we observed 2 to 32-fold increased expression of different transcripts. Real-time PCR confirmed reliability of microarray data. This enabled us to classify and cluster genes by functional families as well as to understand known genes in signaling pathways. These results defined a list of primary candidates for finding novel genes as ‘targets’ for therapeutic intervention

A Holling-Tanner predator-prey model with strong Allee effect

We analyse a modified Holling-Tanner predator-prey model where the predation functional response is of Holling type II and we incorporate a strong Allee effect associated with the prey species production. The analysis complements results of previous articles by Saez and Gonzalez-Olivares (SIAM J. Appl. Math. 59 1867-1878, 1999) and Arancibia-Ibarra and Gonzalez-Olivares (Proc. CMMSE 2015 130-141, 2015)discussing Holling-Tanner models which incorporate a weak Allee effect. The extended model exhibits rich dynamics and we prove the existence of separatrices in the phase plane separating basins of attraction related to co-existence and extinction of the species. We also show the existence of a homoclinic curve that degenerates to form a limit cycle and discuss numerous potential bifurcations such as saddle-node, Hopf, and Bogadonov-Takens bifurcations

Lafora disease offers a unique window into neuronal glycogen metabolism

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase

Intensive care unit-related fluconazole use in Spain and Germany: patient characteristics and outcomes of a prospective multicenter longitudinal observational study

Background: Candida spp. are a frequent cause of nosocomial bloodstream infections worldwide. Objective: To evaluate the use patterns and outcomes associated with intravenous (IV) fluconazole therapy in intensive care units in Spain and Germany. Patients and methods: The research reported here was a prospective multicenter longitudinal observational study in adult intensive care unit patients receiving IV fluconazole. Demographic, microbiologic, therapy success, length of hospital stay, adverse event, and all-cause mortality data were collected at 14 sites in Spain and five in Germany, from February 2004 to November 2005. Results: Patients (n = 303) received prophylaxis (n = 29), empiric therapy (n = 140), preemptive therapy (n = 85), or definitive therapy (n = 49). A total of 298 patients (98.4%) were treated with IV fluconazole as first-line therapy. The treating physicians judged therapy successful in 66% of prophylactic, 55% of empiric, 45% of preemptive, and 43% of definitive group patients. In the subgroup of 152 patients with proven and specified Candida infection only, 32% suffered from Candida specified as potentially resistant to IV fluconazole. The overall mortality rate was 42%. Conclusion: Our study informs treatment decision makers that approximately 32% of the patients with microbiological results available suffered from Candida specified as potentially resistant to IV fluconazole, highlighting the importance of appropriate therapy

Active split-ring metamaterial slabs for magnetic resonance imaging

In this work, it is analyzed the ability of split-ring metamaterial slabs with zero/high permeability to reject/confine the radiofrequency magnetic field in magnetic resonance imaging systems. Using an homogenization procedure, split-ring slabs have been designed and fabricated to work in a 1.5T system. Active elements consisting of pairs of crossed diodes are inserted in the split-rings. With these elements, the permeability of the slabs can be automatically switched between a unity value when interacting with the strong excitation field of the transmitting body coil, and zero or high values when interacting with the weak field produced by protons in tissue. Experiments are shown for different configurations where these slabs can help to locally increase the signal-to-noise-ratio.Comment: 6 pages, 4 figure

Neisseria oralis sp. nov., isolated from healthy gingival plaque and clinical samples

A polyphasic analysis was undertaken of seven independent isolates of Gram-negative cocci collected from pathological clinical samples from New York, Louisiana, Florida and Illinois and healthy subgingival plaque from a patient in Virginia, USA. The 16S rRNA gene sequence similarity among these isolates was 99.7–100 %, and the closest species with a validly published name was Neisseria lactamica (96.9 % similarity to the type strain). DNA–DNA hybridization confirmed that these isolates are of the same species and are distinct from their nearest phylogenetic neighbour, N. lactamica. Phylogenetic analysis of 16S and 23S rRNA gene sequences indicated that the novel species belongs in the genus Neisseria. The predominant cellular fatty acids were C16 : 0, summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH) and C18 : 1ω7c. The cellular fatty acid profile, together with other phenotypic characters, further supports the inclusion of the novel species in the genus Neisseria. The name Neisseria oralis sp. nov. (type strain 6332T = DSM 25276T = LMG 26725T) is proposed

Effects of Medicare Payment Reform: Evidence from the Home Health Interim and Prospective Payment Systems

Medicare continues to implement payment reforms that shift reimbursement from fee-for-service towards episode-based payment, affecting average and marginal reimbursement. We contrast the effects of two reforms for home health agencies. The Home Health Interim Payment System in 1997 lowered both types of reimbursement; our conceptual model predicts a decline in the likelihood of use and costs, both of which we find. The Home Health Prospective Payment System in 2000 raised average but lowered marginal reimbursement with theoretically ambiguous effects; we find a modest increase in use and costs. We find little substantive effect of either policy on readmissions or mortality