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Methicillin-resistant Staphylococcus aureus: interstate spread of nosocomial infections with emergence of gentamicin-methicillin resistant strains.

A methicillin-resistant strain of Staphylococcus aureus (MRSA, phage type 84/85) was introduced into City of Memphis Hospital by a burn patient who had recently been treated for MRSA bacteremia in another institution 500 miles distant. Despite prompt recognition of the problem and institution of isolation procedures, six other patients developed secondary colonization during the ensuing six months, and five of these experienced clinically significant infections with MRSA. Three of the patients originally infected with MRSA, as well as two additional patients, subsequently developed colonization with staphylococcal strains of phage type 84/85 that were resistant to both methicillin and gentamicin (MRGRSA). Spread of the staphylococcal strains was most likely accomplished primarily via passive transfer from person to person. The hydrotherapy unit, which became contaminated with both MRSA and MRGRSA, may have played a secondary role. As illustrated by this outbreak, patients carrying potentially dangerous bacterial strains should be identified and informed of the problems posed by such carriage. It may be imprudent to admit such patients to hospitals that are free of the potential pathogen. The outbreak described here exemplifies a number of potential problems associated with control of nosocomial staphylococcal infections: (a) interhospital spread of methicillin-resistant strains; (b) secondary patient-to-patient intrahospital spread; and (c) emergence of even more resistant strains, possibly associated with selective pressures exerted by widespread use of broad-spectrum antimicrobial agents.

Cross Infection↗

Transmission of Helicobacter spp. A challenge to the dogma of faecal-oral spread.

Faecal oral spread is claimed by many to be the mode of transmission of the gastric pathogen Helicobacter pylori. This idea is based not on experimental data but because the epidemiology of H. pylori infection resembles that of other pathogens known to be spread by the faecal-oral route. This is in spite of the observation that no-one has been successful in culturing H. pylori from human stool. In this study, a series of transmission experiments are reported on animals infected with the gastric spirilla, Helicobacter felis and 'Gastrospirillum hominis'. Germfree mice and rats infected with H. felis did not transmit their infection to uninoculated mice despite prolonged contact in the same cage nor could the bacterium be isolated from their intestinal contents. This was confirmed in specific pathogen free mice where infected dams did not pass the helicobacter to their progeny. Similarly, mice infected with a human isolate of 'Gastrospirillum hominis' did not transmit the infection while in close contact with uninoculated mice. In contrast, in a limited series of experiments, both H. pylori and H. felis were transmitted from infected gnotobiotic Beagle puppies to uninfected animals in the same enclosure. In addition, the gastric mucus from a cat with indigenous 'Gastrospirillum'-like organisms was infectious for mice, whereas faecal content from the same animal was not. It is suggested that the difference between the murine and canine experiments is that the dogs are more likely to have oral-oral contact than rodents. Unlike dogs, mice and rats do not vomit and are coprophagous. It is concluded that the case for faecal-oral spread of Helicobacter species is 'not proven' and that the inter-oral route is more likely.

Animals↗

Re-assessing the likelihood of airborne spread of foot-and-mouth disease at the start of the 1967-1968 UK foot-and-mouth disease epidemic.

The likelihood of airborne spread of foot-and-mouth disease at the start of the 1967-1968 epidemic is re-assessed in the light of current understanding of airborne disease spread. The findings strongly confirm those made at the time that airborne virus was the most likely cause of the rapid early development of the disease out to 60 km from the source. This conclusion is reached following a detailed epidemiological, meteorological and modelling study using original records and current modelling techniques. The role played by 'lee waves' as the mechanism for the spread is investigated. It is thought that they played little part in influencing the development of the epidemic. A number of lessons learned from the work are drawn, identifying the need for further research on the quantity and characteristics of airborne virus. The results are also used to illustrate what advice would have been available to disease controllers if the outbreak had occurred in 2004.

Air Microbiology↗

Investigating the potential spread of infectious diseases of sheep via agricultural shows in Great Britain.

The rate at which infectious diseases spread through farm animal populations depends both on individual disease characteristics and the opportunity for transmission via close contact. Data on the relationships affecting the contact structure of farm animal populations are, therefore, required to improve mathematical models for the spatial spread of farm animal diseases. This paper presents data on the contact network for agricultural shows in Great Britain, whereby a link between two shows occurs if they share common competitors in the sheep class. Using the network, the potential for disease spread through agricultural shows is investigated varying both the initial show infected and the infectious period of the disease. The analysis reveals a highly connected network such that diseases introduced early in the show season could present a risk to sheep at the majority of subsequent shows. This data emphasizes the importance of maintaining rigorous showground and farm-level bio-security.

Agriculture↗

Asymmetrical dynamics of voltage spread in retinal horizontal cell networks.

Lateral voltage spread in electrically coupled retinal horizontal cell networks is the substrate of center-surround antagonism in bipolar and ganglion cells. We studied its spatial and temporal properties in more detail in turtle L1 horizontal cells by using a contrast border as light stimulus. Experimental data were contrasted with expectations from a linear continuum model to specify the impact of nonlinearities. The assumptions for the diffusion term of the continuum model were justified by neurobiotin labeling. Measured voltage spread revealed two different length constants lambda+ and lambda0, under illuminated and nonilluminated regions of the retina, respectively, as predicted by the linear model. Length constants in the illuminated region showed strong temporal dynamics. For the initial phase of the horizontal cell responses lambda+ was larger than lambda0. This was also in accordance with the model. Right at the peak of the response, however, lambda+ dropped below lambda0 and did not change any more. It is this temporal reversal of asymmetry in voltage spread and not the decrease of lambda+ itself that is lacked by the linear model. The observed independence of the mean ratio lambda+/lambda0 from light intensity in both the peak and the plateau phases of horizontal cell responses contradicts the linear assumption, too. These two effects have to be addressed to local nonlinearities in the horizontal cell network like a negative feedback loop from photoreceptors and/or voltage-dependent conductances. Due to the failure of the linear model, firm conclusions about the membrane resistance and the coupling resistance of the horizontal cell network cannot be drawn from length constant measurements.

Animals↗

Mac-1 promotes FcgammaRIIA-dependent cell spreading and migration on immune complexes.

The integrin Mac-1 plays a critical role in Fc receptor (FcR)-mediated antibody-dependent cellular cytotoxicity (ADCC). However, the mechanism by which Mac-1 facilitates the functions of FcgammaRIIA, a major FcR expressed on human leukocytes, is not fully understood. We report here that Mac-1 sustains cell adhesion, enhances cell spreading, and accelerates cell migration on preformed immune complexes (ICs) by directly interacting with FcgammaRIIA but not with the IC substrate. Coupling Mac-1 to FcgammaRIIA allows FcgammaRIIA to reside in the leading front of actin polymerization at the filopodial extension and thus could potentially enhance FcgammaRIIA-mediated cell spreading and migration. The direct interaction between Mac-1 and FcgammaRIIA is demonstrated by co-immunoprecipitation, by cell surface co-localization, and by solid-phase binding assays using recombinant alpha(M)I-domain and soluble FcgammaRIIA. Further mutational analysis identifies the E(253)-R(261) sequence within the alpha(M)I-domain as part of the FcgammaRIIA binding interface within Mac-1. Altogether, these results demonstrate that FcgammaRIIA recognizes Mac-1 via the alpha(M)I-domain but not the lectin domain, a distinct feature from other FcRs, and that Mac-1 binding confers FcgammaRIIA with the ability to prolong cell adhesion as well as to spread and migrate on the ICs, leading to effective cell killing by ADCC.

Antigen-Antibody Complex↗

Scanning Raman spectroscopy for characterizing compositionally spread films.

Composition-spread La(1-x)SrxMnO3 thin films were prepared by pulsed laser deposition technique from LaMnO3 and SrMnO3 targets. The films were epitaxial with a continuous variation of the out-of-plane lattice parameter along the direction of composition gradient. Scanning Raman spectroscopy has been employed as a nondestructive tool to characterize the composition-spread films. Raman spectra showed the variation of the structural, Jahn Teller distortions and the presence of coexisting phases at particular compositions that are in agreement with the previous observation on the single-crystal samples. Raman spectra on the continuous composition-spread film also reveal the effect of disorder and strain on the compositions.

Spectrum Analysis, Raman↗

Molecular level study of the formation and the spread of MoO3 on Au(111) by scanning tunneling microscopy and X-ray photoelectron spectroscopy.

The formation of MoO(3) and its spontaneous spread over an Au (111) surface have been studied by X-ray photoelectron spectroscopy (XPS) and scanning tunneling microscopy (STM). Metallic Mo clusters grown by Mo(CO)(6) chemical vapor deposition (CVD) have a constant size independent of the Mo coverage. Molecular oxygen does not react with low coverage of Mo, probably due to the encapsulation of the Mo clusters by Au. At higher coverage, O(2) reacts with Mo, partially transforming the metallic Mo to Mo(4+). NO(2) can oxidize Mo efficiently to Mo(6+) and Mo(5+) species at all coverages investigated. XPS experiments show that the integrated intensity of the Mo 3d peaks increases by a factor of 2 upon the oxidation, suggesting the spread of the MoO(3) over the surface. The STM study confirms this suggestion and provides the mechanistic details of the spreading. Mo oxide forms ramified two-dimensional islands covering a substantially larger fraction of the Au surface than the metallic Mo. We propose that the morphology change starts with the diffusion of oxide clusters (ramified-cluster-diffusion mechanism), followed by their breakdown to highly disordered two-dimensional islands of molecular MoO(3).

Journal Article↗

Controlling primary hepatocyte adhesion and spreading on protein-free polyelectrolyte multilayer films.

The development of new methods for fabricating thin films that provide precise control of the three-dimensional topography and cell adhesion could lead to significant advances in the fields of tissue engineering and biosensors. This Communication describes the successful attachment and spreading of primary hepatocytes on polyelectrolyte multilayer (PEM) films without the use of adhesive proteins such as collagen or fibronectin. We demonstrate that the attachment and spreading of primary hepatocytes can be controlled using this layer-by-layer deposition of ionic polymers. In our study, we used synthetic polymers, namely poly(diallyldimethylammonium chloride) (PDAC) and sulfonated poly(styrene) (SPS) as the polycation and polyanion, respectively, to build the multilayers. Primary hepatocytes attached and spread preferentially on SPS surfaces over PDAC surfaces. SPS patterns were formed on PEM surfaces, either by microcontact printing of SPS onto PDAC surfaces or vice versa, to obtain patterns of primary hepatocytes. PEM is a useful technique for fabricating controlled co-cultures with specified cell-cell and cell-surface interactions on a protein-free environment, thus providing flexibility in designing cell-specific surfaces for tissue engineering applications.

Animals↗

Droplet spreading on microstriped surfaces.

When a droplet of fluid is deposited on a surface with chemical and/or topological patterns, its static shape is highly dependent on the 2D distribution of the patterns. In the case of chemical stripes, three distinct spreading regimes have been observed as a function of wettability contrast between the two kind of stripes. For low wettability contrast, the droplet spreads with the same [corrected] velocity normal and parallel to the stripes [corrected] and the macroscopic contact angle is close to Cassie's contact angle. When the wettability contrast is intermediate/high, the resulting shape of the droplets is elongated. In the intermediate wettability contrast regime, an ideal situation shows stick and slip behavior of the contact line, during which the contact line jumps from one stripe to another. For a high wettability contrast, the confinement of the fluid between two chemical stripes leads to a 2D spreading.

Journal Article↗

Contact line dynamics in drop coalescence and spreading.

The dynamics of coalescence of two water sessile drops is investigated and compared with the spreading dynamics of a single drop in partially wetting regime. The composite drop formed due to coalescence relaxes exponentially toward equilibrium with a typical relaxation time that decreases with contact angle. The relaxation time can reach a few tenths of seconds and depends also on the drop size, initial conditions, and surface properties (contact angle, roughness). The relaxation dynamics is larger by 5 to 6 orders of magnitude than the bulk hydrodynamics predicts, due to the high dissipation in the contact line vicinity. The coalescence is initiated at a contact of the drops growing in a condensation chamber or by depositing a small drop at the top of neighboring drops with a syringe, a method also used for the studies of the spreading. The dynamics is systematically faster by an order of magnitude when comparing the syringe deposition with condensation. We explain this faster dynamics by the influence of the unavoidable drop oscillations observed with fast camera filming. Right after the syringe deposition, the drop is vigorously excited by deformation modes, favoring the contact line motion. This excitation is also observed in spreading experiments while it is absent during the condensation-induced coalescence.

Journal Article↗

Giant lipid vesicles impaled with glass microelectrodes: GigaOhm seal by membrane spreading.

Giant unilamellar lipid vesicles could be perfect systems to study ion channels in the environment of lipid membranes with defined chemical and physical properties. Prerequisite for electrical measurements is an intravesicular electrical contact. We describe the impalement of giant lipid vesicles by glass micropipet electrodes with a tight seal. To avoid displacement or burst during impalement, the vesicles are immobilized in relaxed conditions by microscopic picket fences of polyimide. The outer surface of the pipets is selectively coated with silanes or polylysine. Structurally, the impalement is verified by ejecting a fluorescent solution out of the pipet. For electrical characterization, current pulses are applied to the pipet and voltage transients are recorded. The data are evaluated in terms of the capacitance and effective resistance of the membrane. Directly after impalement, we observe a seal resistance up to 1.2 GOmega that continuously decays within a period of up to 20 min until it suddenly disappears without burst of the vesicle. During impalement, a spreading of the vesicle membrane along the outer surface of the pipets is observed using a fluorescent membrane-bound dye. We assign the tight pipet-vesicle contact to spreading of the lipid bilayer by a rolling mechanism and the loss of resistance to micro- and macropores that are induced by the resulting membrane tension. Limitation of spreading is attempted with barriers on the pipet.

Electric Impedance↗

Spontaneous spreading of nematic liquid crystals.

The spontaneous spreading of macroscopic drops of nematic liquid crystals on hydrophilic substrates has been investigated by interferometric techniques. There is a complex interplay between the elastic energy, due to antagonist anchoring at the interfaces, and the radial flow in the spreading drop. A relevant parameter appears to be the relative humidity of the atmosphere, because it controls the amount of water molecules adsorbed on the substrate and, therefore, the strength of anchoring defects. The spreading laws differ from the ones of simple wetting liquids, and contact line instabilities coupled to short- (anchoring) or large-scale (disclinations) defects of the nematic film are observed.

Journal Article↗

Molecular dynamics study of the influence of surfactant structure on surfactant-facilitated spreading of droplets on solid surfaces.

The spreading of a partially wetting aqueous drop in air on a hydrophobic surface can be facilitated by the adsorption of surfactants from the drop phase onto the air/aqueous and aqueous/hydrophobic solid interfaces of the drop. At the contact line at which these interfaces meet, conventional surfactants with a linear alkyl hydrophobic chain attached to a polar group adsorb onto the surfaces, forming monolayers which remain distinct as they merge at the contact juncture. The adsorption causes a decrease in the interfacial tensions and reduction in the contact angle but the angle remains above zero so the drop is still nonwetting. Trisiloxane surfactants with a T-shaped geometry in which the hydrophobic group is composed of a trisiloxane oligomer with a polar group attached at the center of the chain can give rise to a zero contact angle at the contact line and complete wetting (superspreading). Experimental evidence suggests the adsorption of the T-shaped molecule, in addition to significantly decreasing the tensions of the interfaces (relative to the conventional surfactants), promotes the formation of a precursor film consisting of a surfactant bilayer at the contact line which facilitates the spreading. The aim of this study is to use molecular dynamics to examine if the T-shaped structure can promote spreading by the formation of a bilayer and to contrast this case with that of the linear chain surfactant where complex assembly does not occur. The simulation models the solvent as a monatomic liquid, the substrate as a particle lattice, and the surfactants as united atom structures, with all interactions given by Lennard-Jones potentials. We start with a base case in which the solvent partially wets a substrate comprised of a lattice of particles. We demonstrate that adsorbed T-shaped surfactant monolayers can, when the interaction between the solvent and the hydrophile particles is strong enough, assemble into a bilayer, allowing the drop to extend to a thin planar film. In the case of the flexible linear chain surfactant, there is no interaction between the monolayers on the two interfaces in the case of a strong hydrophile-solvent interaction and less coordination for a weaker interaction. In either case, the monolayers remain distinct, as the surfactant only marginally improves wetting.

Models, Molecular↗

A computer model of the spread of hepatitis C virus among injecting drug users.

A number of behavioural and clinical parameters influence the transmission of an infectious agent through direct contact between two individuals. The behavioural parameters encountered in such situations are also likely to exhibit an enormous amount of variability. With the spread of hepatitis C among injecting drug users, the parameters associated with injecting behaviour play an important role in the modelling of the transmission process. Computer simulation modelling is an ideal approach to deal with a large number of parameters as well as high levels of variability without excessive simplification. The simulation model presented in this paper is tested on data from a cohort of injecting drug users and the results obtained are very encouraging from a public health perspective. The model clearly indicates that the rate at which HCV spreads through a population of injecting drug users is extremely sensitive to the interaction rate and to the probability of infection through a single contact with an infective. At the same time it shows that rate of spread is not very sensitive to initial prevalence, which is very encouraging from a public health perspective.

Computer Simulation↗

A filter that prevents the spread of mail-attachment-type Trojan horse computer worms.

The malicious code "W32/Sircam" is spread via e-mail and potentially through the file space shared by local area networks. Such Trojan-horse-type computer worms easily penetrate Internet firewalls and propagate via the "backdoor" to other computers. Once a malicious code, such as "W32/Sircam," has been executed on a system, it may reveal or delete confidential data, such as clinical records. In order to protect against the leakage of clinical records, we devised a mail filter that successfully prevents the spread of mail containing this malicious code. It is significant that neither access control nor packet filtering is guaranteed to prevent the spread of this mail-attachment-type Trojan horse computer worm.

Computer Communication Networks↗

Humoral epitope-spreading following immunization with a HER-2/neu peptide based vaccine in cancer patients.

HER-2/neu is a tumor antigen in patients with breast and ovarian cancer. Multiple varieties of vaccine strategies are being developed to immunize patients against HER-2/neu. Studies in animal models have demonstrated both T cell and antibody immunity are needed to mediate an antitumor response. Thirty-five patients, immunized with HER-2/neu peptide based vaccines, were evaluated for the generation of HER-2/neu-specific antibody immunity. Sixty percent of patients developed HER-2/neu IgG specific antibody responses to at least one peptide included in their vaccine. Twenty-nine percent of patients developed IgG immunity to the native HER-2/neu protein after peptide immunization. Humoral intramolecular epitope-spreading within the HER-2/neu protein occurred in 49% of immunized patients. Intermolecular epitope-spreading to p53 was evident in 20% of vaccinated patients. Of those patients who developed new immunity to p53, 71% had demonstrated antibody epitope-spreading within HER-2/neu.

Adult↗

Spreading activation versus compound cue accounts of priming: mediated priming revisited.

Spreading activation theories and compound cue theories have both been proposed as accounts of priming phenomena. According to spreading activation theories, the amount of activation that spreads between a prime and a target should be a function of the number of mediating links between the prime and target in a semantic network and the strengths of those links. The amount of activation should determine the amount of facilitation given by a prime to a target in lexical decision. To predict the amount of facilitation, it is necessary to measure the associative links between prime and target in memory. Free-association production probability has been the variable chosen in previous research for this measurement. However, in 3 experiments, the authors show priming effects that free-association production probabilities cannot easily predict. Instead, they argue that amount of priming depends on the familiarity of the prime and target as a compound, where the compound is formed by the simultaneous presence of the prime and target in short-term memory as a test item.

Adult↗