Plaque phenotypes of wild-type, PB2 627E and PB2 627E 701N viruses at 33°C and 37°C.

<p>Plaque assays were performed on MDCK cells incubated at 33°C or 37°C, as indicated at the left of the figure, and immunostained with virus-specific antibody. (A) Plaque phenotypes of rPan99 WT and PB2 mutant viruses. (B) Average plaque diameter for each rPan99 virus is plotted at 33°C and 37°C. (C) Plaque phenotypes of rVN1203 WT and PB2 mutant viruses. (D) Average plaque diameter for each rVN1203 virus is plotted at 33°C and 37°C. Plaque assays of rPan99 viruses and rVN1203 viruses were performed at different times. Error bars indicate standard deviation. * indicates p<0.01 and ** indicates p<0.001, as determined by t-test of plaque diameter values.</p

Amino acids at PB2 positions 627 and 701 of viruses used in this study.

<p>Amino acids at PB2 positions 627 and 701 of viruses used in this study.</p

Guinea pig 50% infectious dose of wild-type and PB2 mutant viruses.

*<p>GPID50 values are shown in units of PFU/guinea pig.</p

Growth kinetics of wild-type, PB2 627E and PB2 627E 701N viruses in MDCK cells incubated at 37°C and 33°C.

<p>(A) and (B) show the results from rPan99-based viruses, while (C) and (D) show the results from rVN1203-based viruses. Titers of the wild-type viruses are shown with squares and solid lines; titers of PB2 627E mutants are shown with triangles and long dashed lines; and titers of PB2 627E 701N viruses are shown with circles and short dashed lines. The MOI of infection in all cases was 0.01 PFU/cell. ** all three viruses are significantly different from each other (p<0.05, Student's t-test). * the titers of both mutants are significantly different from those of the wild-type (p<0.05, Student's t-test). # the titers of the 627E mutant are significantly different from those of both the wild-type and the 627E 701N viruses. † the titers of the 627E 701N double mutant are significantly different from those of both the wild-type and the 627E single mutant viruses.</p

Growth kinetics of rPan99 wild-type, rPan99 627E and rPan99 627E 701N viruses in the upper and lower respiratory tracts of guinea pigs.

<p>(A) Viral titers in nasal wash samples of infected guinea pigs are plotted on days 2 and 4 p.i. On day 2 p.i., titers of the wild-type virus were significantly different from rPan99 627E (p = 0.0020) and from rPan99 627E 701N (p = 0.0057). On day 4 p.i., titers of the wild-type virus were not significantly different from those of either PB2 mutant virus (p≥0.03). (B) Titers of virus recovered from the supernatant of homogenized lung tissue at 2 d and 4 d p.i. Virus in three tissue samples from each of two animals was quantified; titers from one guinea pig are shown with open squares and titers from the second guinea pig are shown with closed diamonds. Titers of the wild-type virus were not significantly different from rPan99 627E (p = 0.39 on day 2 and p = 0.011 on day 4) or from rPan99 627E 701N (p = 0.067 on day 2 and p = 0.025 on day 4). All p-values were determined by Student's t-test. * indicates a significant difference relative to the wild-type, with p<0.01 as determined by Student's t-test. The mean and standard deviation for each data set are shown above the corresponding data points.</p

Contact transmission of rVN1203 wild-type, rVN1203 627E and rVN1203 627E 701N viruses in guinea pigs.

<p>Nasal wash titers are plotted as a function of time post-inoculation. Titers of intranasally inoculated animals are represented by dashed lines and filled squares; titers of exposed guinea pigs are shown with solid lines and filled triangles. (A) Transmission of rVN1203 wild-type virus. (B) Transmission of the rVN1203 627E mutant. (C) Transmission of the rVN1203 627E 701N double mutant.</p

Virus detection and seroconversion in guinea pigs inoculated or exposed as part of rPan99 virus transmission experiments.

*<p>limit of detection was 10 PFU/ml.</p>**<p>seroconversion was defined as a ≥4-fold increase in hemagglutination-inhibition titer.</p>#<p>n/a not applicable; a third experiment was not performed with rPan99 wild-type.</p

Pulsed ultraviolet light decontamination of virus-laden airstreams

<p>Continuous ultraviolet germicidal irradiation (UVGI) has been extensively studied, but research on pulsed UVGI (PUVGI) is lacking and has primarily focused on disinfection of solid surfaces or liquids. This study addressed the gap in knowledge on the effectiveness of pulsed UVGI for disinfecting virus-laden calm air, with relevance to indoor rooms. Φ6 bacteriophage (a surrogate used to study communicable enveloped human respiratory viral pathogens such as influenza virus) was aerosolized by a Collison device into an enclosed test chamber, wherein the bioaerosol was exposed to PUVGI. The spectral content and performance of a pulsed white light lamp with a substantial UVC component were defined. Pulsed UV exposure of 10 to 30 s resulted in a two-log reduction in viable recovered virus from filter membranes and cyclone-based samplers. The small differences in Φ6 survival, after 10 to 30 s of exposure, emphasized the difficulty of complete eradication. However, exposure to 10 s of PUVGI resulted in significant reduction of virus viability. The dose–response displayed clear regimes of fast and slow exponential decay. Susceptibility factor for the fast-decay regime of aerosolized Φ6 (<i>Z</i> = 0.24 m²/J) was similar to those reported for influenza A virus aerosols at similar relative humidity. Our study demonstrated the potency of PUVGI against a viral bioaerosol. This has potential implications for the control of infectious bioaerosols in the healthcare setting.</p> <p>© 2017 American Association for Aerosol Research</p

Mesenchymal Stromal (Stem) Cell Therapy Fails to Improve Outcomes in Experimental Severe Influenza

<div><p>Rationale</p><p>Severe influenza remains a major public health threat and is responsible for thousands of deaths annually. Increasing antiviral resistance and limited effectiveness of current therapies highlight the need for new approaches to influenza treatment. Extensive pre-clinical data have shown that mesenchymal stromal (stem) cell (MSC) therapy can induce anti-inflammatory effects and enhance repair of the injured lung. We hypothesized that MSC therapy would improve survival, dampen lung inflammation and decrease acute lung injury (ALI) in a murine model of severe influenza<b>.</b></p><p>Methods</p><p>C57Bl/6 mice were infected with influenza A/PuertoRico/8/34 (mouse-adapted H1N1) or influenza A/Mexico/4108/2009 (swine-origin pandemic H1N1) and administered human or mouse MSCs via the tail vein, either pre- or post- infection. MSC efficacy was evaluated as both an independent and adjunctive treatment strategy in combination with the antiviral agent, oseltamivir. Weight loss and survival were monitored. Inflammatory cells, cytokine/chemokines (IFN-γ, CXCL10, CCL2 and CCL5) and markers of ALI (total protein and IgM), were measured in bronchoalveolar lavage fluid and lung parenchyma.</p><p>Results</p><p>Administration of murine MSCs or human MSCs in a prophylactic or therapeutic regimen failed to improve survival, decrease pulmonary inflammation/inflammatory cell counts or prevent ALI in influenza virus-infected mice. MSCs administered in combination with oseltamivir also failed to improve outcomes.</p><p>Conclusions</p><p>Despite similarities in the clinical presentation and pathobiology of ALI and severe influenza, our findings suggest that MSC therapy may not be effective for prevention and/or treatment of acute severe influenza.</p></div

Comparing the ethical challenges of forgoing tube feeding in American and Hong Kong Chinese residents with advanced dementia

2007 World Congress on Ageing and Dementia in Chinese Communities, Hong Kong, 7-10 March 20072006-2007 > Academic research: refereed > Invited conference pape