Accuracy of the Unipolar Electrogram for Identification of the Site of Origin of Ventricular Activation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73873/1/j.1540-8167.1997.tb00619.x.pd

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

Premature ventricular contractions originating from the left ventricular septum: Results of Radiofrequency Catheter Ablation in twenty patients

<p>Abstract</p> <p>Background</p> <p>RFCA has been established as an effective and curative therapy for severely symptomatic PVC from the outflow tract in structurally normal hearts. However, it is unknown whether PVCs originating from the left ventricular septum, are effectively eliminated by RFCA. This study aimed to investigate electrophysiologic characteristics and effects of Radiofrequency catheter ablation (RFCA) for patients with symptomatic premature ventricular contraction (PVC) originating from the left ventricular septum without including fascicular PVCs.</p> <p>Methods</p> <p>Characteristics of body surface electrocardiogram (ECG) and electrophysiologic recordings endocardiogram in a successful RFCA target were analyzed in 20 patients with symptomatic PVCs originating from the left ventricular septum. RFCA was performed using pace mapping and activation mapping.</p> <p>Results</p> <p>The QRS morphology of PVCs originating from the left ventricular septum is similar to that seen in fascicular tachycardia. Most of the PVCs originated from the left septum appears in the form of ventricular parasystole. The incidence of ventricular parasystole was 70%. Sustained ventricular tachycardia was not inducible by electrical stimulation and isoproterenol infusion in all 20 patients, ablation at the site recording the earliest Purkinje potential was not effective in all 20 patients, and Purkinje potentials were not identified at successful sites during point mapping. Sixteen patients were successful with RFCA using pace mapping and activation mapping, 3 failed, and 1 recurrent.</p> <p>Conclusion</p> <p>Although the ECG characteristics of the PVCs arising from the left ventricular septum are similar to that seen in fascicular tachycardia, the electrophysiologic characteristics are different between the two types of PVCs. The distinguishing characteristic of the PVCs is that Purkinje potentials were not present at the site of successful ablation, suggesting a myocardial as opposed to fascicular substrate. RFCA is an effective curative therapy for symptomatic PVCs originating from the left ventricular septum (not from the left anterior and posterior fascicle).</p

Camouflaging in a Complex Environment—Octopuses Use Specific Features of Their Surroundings for Background Matching

Living under intense predation pressure, octopuses evolved an effective and impressive camouflaging ability that exploits features of their surroundings to enable them to “blend in.” To achieve such background matching, an animal may use general resemblance and reproduce characteristics of its entire surroundings, or it may imitate a specific object in its immediate environment. Using image analysis algorithms, we examined correlations between octopuses and their backgrounds. Field experiments show that when camouflaging, Octopus cyanea and O. vulgaris base their body patterns on selected features of nearby objects rather than attempting to match a large field of view. Such an approach enables the octopus to camouflage in partly occluded environments and to solve the problem of differences in appearance as a function of the viewing inclination of the observer

Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis

Phosphoenol pyruvate is the highest-energy phosphate found in living organisms and is one of the most versatile molecules in metabolism. Consequently, it is an essential intermediate in a wide variety of biochemical pathways, including carbon fixation, the shikimate pathway, substrate-level phosphorylation, gluconeogenesis and glycolysis. Triose glycolysis (generation of ATP from glyceraldehyde 3-phosphate via phosphoenol pyruvate) is among the most central and highly conserved pathways in metabolism. Here, we demonstrate the efficient and robust synthesis of phosphoenol pyruvate from prebiotic nucleotide precursors, glycolaldehyde and glyceraldehyde. Furthermore, phosphoenol pyruvate is derived within an α-phosphorylation controlled reaction network that gives access to glyceric acid 2-phosphate, glyceric acid 3-phosphate, phosphoserine and pyruvate. Our results demonstrate that the key components of a core metabolic pathway central to energy transduction and amino acid, sugar, nucleotide and lipid biosyntheses can be reconstituted in high yield under mild, prebiotically plausible conditions

Can we improve outcome of congenital diaphragmatic hernia?

This review gives an overview of the disease spectrum of congenital diaphragmatic hernia (CDH). Etiological factors, prenatal predictors of survival, new treatment strategies and long-term morbidity are described. Early recognition of problems and improvement of treatment strategies in CDH patients may increase survival and prevent secondary morbidity. Multidisciplinary healthcare is necessary to improve healthcare for CDH patients. Absence of international therapy guidelines, lack of evidence of many therapeutic modalities and the relative low number of CDH patients calls for cooperation between centers with an expertise in the treatment of CDH patients. The international CDH Euro-Consortium is an example of such a collaborative network, which enhances exchange of knowledge, future research and development of treatment protocols

Osteopathology and selenium deficiency co-occurring in a population of endangered Patagonian huemul (Hippocamelus bisulcus)

Background: About 1,000 endangered Patagonian huemul deer (Hippocamelus bisulcus) remain in Chile and 350-500 in Argentina. Most groups (&gt;100) are not recovering, and prevalence of osteopathology in Argentina was at least 57%. Here I describe relevant cases of osteopathology from a Chilean population which, however, recently also provided data on trace mineral status, supporting the initial hypothesis that nutrition may be a primary etiologic factor. Additionally, recent data on bone chemical composition of Argentine cases and soil analyses are discussed. Results: Fluoride levels in Argentine cases with osteopathology were low and fluorosis was discarded as an etiological factor. Selenium deficiency occurred in 73% of huemul from the Chilean population which exhibited several cases with osteopathology. The pathophysiognomy included extensive erosion; tooth loss;  porosification; perforations of palate, maxillar and mandibular bone with frequent exposure of tooth roots; and fractured mandibula. Areas currently used by remaining huemul have mainly acidic volcanic soils, which reduces selenium bioavailability: mean soil selenium levels from areas typically used by extant huemul were very deficient (0.19 ppm), corroborating documented overt selenium deficiency in local livestock and plants. The area of extant huemul is known to result in primary iodine deficiency in livestock which is aggravated by selenium deficiency. Conclusions: Currently the most parsimonious explanation for frequent osteopathology and lack of numerical recovery are the combined effects of selenium and iodine deficiencies based on: osteopathology in a population of selenium deficient huemul; selenium deficient livestock, plants and soils; acidic soils; and regional primary iodine deficiency. The nexus between mineral nutrition and population dynamics of huemul may be due to constraints on their movements to fertile lowlands, including the elimination of historic migratory traditions, and concomitant elimination of source populations