Mobile Healthcare Design Research: A Special Issue for Information Systems Researchers

Special Section Editorial - Mobile Decision Support and Analytics for Healthcare: Citizen, Organization, Governmental and Technological Perspective

The Importance of Attributional Trust to Corporate Reputation

This article proposes the simplified trust-reputation model that relates attributional trust and issue resolution to corporate reputation. In effect, individuals on a project are very forgiving of supply chain members with regard to issues because of concern for their company's reputation. Hence, while trust may vary, there was no breakdown in trust because this would affect their company's reputation as a good partner. Furthermore, although there was a reported variance in trust by the project managers, it did not affect the project's outcome, but it did affect the ease of doing business

Effects of Hepatic Ischemia-Reperfusion Injury on the Blood-Brain Barrier Permeability to [14C] and [13C]Sucrose

Hepatic encephalopathy that is associated with severe liver failure may compromise the blood-brain barrier (BBB) integrity. However, the effects of less severe liver diseases, in the absence of overt encephalopathy, on the BBB are not well understood. The goal of the current study was to investigate the effects of hepatic ischemia-reperfusion (IR) injury on the BBB tight junction permeability to small, hydrophilic molecules using the widely used [14C]sucrose and recently-proposed alternative [13C]sucrose as markers. Rats were subjected to 20 min of hepatic ischemia or sham surgery, followed by 8 h of reperfusion before administration of a single bolus dose of [14C] or [13C]sucrose and collection of serial (0–30 min) blood and plasma and terminal brain samples. The concentrations of [14C] and [13C]sucrose in the samples were determined by measurement of total radioactivity (nonspecific) and LC-MS/MS (specific), respectively. IR injury significantly increased the blood, plasma, and brain concentrations of both [14C] and [13C]sucrose. However, when the brain concentrations were corrected for their respective area under the blood concentration-time curve, only [14C]sucrose showed significantly higher (30%) BBB permeability values in the IR animals. Because [13C]sucrose is a more specific BBB permeability marker, these data indicate that our animal model of hepatic IR injury does not affect the BBB tight junction permeability to small, hydrophilic molecules. Methodological differences among studies of the effects of liver diseases on the BBB permeability may confound the conclusions of such studies

1H CSA parameters by ultrafast MAS NMR: measurement and applications to structure refinement

A 1H anisotropic-isotropic chemical shift correlation experiment which employs symmetry-based recoupling sequences to reintroduce the chemical shift anisotropy in ν1 and ultrafast MAS to resolve 1H sites in ν2 is described. This experiment is used to measure 1H shift parameters for L-ascorbic acid, a compound with a relatively complex hydrogen-bonding network in the solid. The 1H CSAs of hydrogen-bonded sites with resolved isotropic shifts can be extracted directly from the recoupled lineshapes. In combination with DFT calculations, hydrogen positions in crystal structures obtained from X-ray and neutron diffraction are refined by comparison with simulations of the full two-dimensional NMR spectrum. The improved resolution afforded by the second dimension allows even unresolved hydrogen-bonded sites 1H to be assigned and their shift parameters to be obtained

Effects of Hepatic Ischemia-Reperfusion Injury on the P-Glycoprotein Activity at the Liver Canalicular Membrane and Blood-Brain Barrier Determined by In Vivo Administration of Rhodamine 123 in Rats

Purpose To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood-brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker. Methods Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis. Results P-gp protein levels at the liver canalicular membrane were increased by twofold after 24 h of reperfusion. However, the biliary excretion of RH-123 was reduced in these rats by 26%, presumably due to IR-induced reductions in the liver uptake of the marker and hepatic ATP concentrations. At the BBB, a 24% overexpression of P-gp in the 24-h IR animals was associated with a 30% decrease in the apparent brain uptake clearance of RH-123. The pharmacokinetics or brain distribution of RH-123 was not affected by the 12-h IR injury. Conclusions Hepatic IR injury may alter the peripheral pharmacokinetics and brain distribution of drugs that are transported by P-gp and possibly other transporters

Effects of Short-Term Portacaval Anastomosis on the Peripheral and Brain Disposition of the Blood-Brain Barrier Permeability Marker Sodium Fluorescein in Rats

Contradictory results have been reported with regard to the effects of various models of hepatic encephalopathy on the blood-brain barrier (BBB) permeability, which may be due partly to the use of brain concentrations of BBB markers without attention to their peripheral pharmacokinetics. The purpose of the current study was to investigate the effects of short-term portacaval anastomosis (PCA), a type B model of hepatic encephalopathy, on the peripheral pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a small molecule marker of BBB passive permeability. A single 25 mg/kg dose of FL was administered intravenously to 10-day PCA and sham-operated rats, and serial blood and bile (0-30 min) and terminal (30 min) brain samples were collected, and the concentrations of FL and its glucuronidated metabolite (FL-Glu) were measured by HPLC. Additionally, the free fractions of FL (fu) in all the plasma samples were determined, and the effects of bile salts on fu were investigated in vitro. Passive permeability of BBB to FL was estimated by brain uptake clearance (Kin) based on both the brain concentrations of FL and plasma concentrations of free (unbound) FL. PCA caused a 26% increase in the fu of FL in plasma, which was due to competition of bile acids with FL for binding to plasma proteins. Additionally, PCA reduced the biliary excretion of FL-Glu by 55%. However, free Kin values (μl/min/g brain) for the sham (0.265 ± 0.034) and PCA (0.228 ± 0.038) rats were not significantly different. It is concluded that whereas 10-day PCA alters the peripheral pharmacokinetics of FL, it does not significantly affect the BBB permeability to the marker

Evaluation of [14C] and [13C]Sucrose as Blood-Brain Barrier Permeability Markers

Non-specific quantitation of [14C]sucrose in blood and brain has been routinely used as a quantitative measure of the in vivo blood-brain barrier (BBB) integrity. However, the reported apparent brain uptake clearance (Kin) of the marker varies widely (∼100 fold). We investigated the accuracy of the use of the marker in comparison with a stable isotope of sucrose ([13C]sucrose) measured by a specific LC-MS/MS method. Rats received single doses of each marker, and the Kin values were determined. Surprisingly, the Kin value of [13C]sucrose was 6-7 fold lower than that of [14C]sucrose. Chromatographic fractionation after in vivo administration of [14C]sucrose indicated that the majority of the brain content of radioactivity belonged to compounds other than the intact [14C]sucrose. However, mechanistic studies failed to reveal any substantial metabolism of the marker. The water: octanol partition coefficient of [14C]sucrose was \u3e 2 fold higher than that of [13C]sucrose, indicating presence of lipid-soluble impurities in the [14C]sucrose solution. Our data indicate that [14C]sucrose overestimates the true BBB permeability to sucrose. We suggest that specific quantitation of the stable isotope (13C) of sucrose is a more accurate alternative to the current widespread use of the radioactive sucrose as a BBB marker

Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution