Focusing the Neuroscience and Societal Implications of Cognitive Enhancers.

Cognitive enhancement can benefit the individual and society, but also has associated risks and ethical concerns. Cognitive-enhancing drugs are used in the treatment of neuropsychiatric disorders. Nonpharmacological strategies are also emerging, which have the potential to improve motivational deficits associated with neuropsychiatric symptoms and should be prioritized for development. The increasing lifestyle use of "smart" and other drugs indicates the desire for healthy people to improve themselves. Safety and ethical implications are discussed.

An alternative method of measuring aerosol survival using spiders' webs and its use for the filoviruses.

Understanding the ability to survive in an aerosol leads to better understanding of the hazard posed by pathogenic organisms and can inform decisions related to the control and management of disease outbreaks. This basic survival information is sometimes lacking for high priority select agents such as the filoviruses which cause severe disease with high case fatality rates and can be acquired through the aerosol route. Microthreads in the form of spiders' webs were used to capture aerosolised filoviruses, and the decay rates of Zaire ebolavirus and Marburgvirus were determined. Results were compared to data obtained using a Goldberg drum to measure survival as a dynamic aerosol. The two methods of obtaining aerostability information are compared.

The survival of filoviruses in liquids, on solid substrates and in a dynamic aerosol.

AIMS: Filoviruses are associated with high morbidity and lethality rates in humans, are capable of human-to-human transmission, via infected material such as blood, and are believed to have low infectious doses for humans. Filoviruses are able to infect via the respiratory route and are lethal at very low doses in experimental animal models, but there is minimal information on how well the filoviruses survive within aerosol particles. There is also little known about how well filoviruses survive in liquids or on solid surfaces which is important in management of patients or samples that have been exposed to filoviruses. METHODS AND RESULTS: Filoviruses were tested for their ability to survive in different liquids and on different solid substrates at different temperatures. The decay rates of filoviruses in a dynamic aerosol were also determined. CONCLUSIONS: Our study has shown that Lake Victoria marburgvirus (MARV) and Zaire ebolavirus (ZEBOV) can survive for long periods in different liquid media and can also be recovered from plastic and glass surfaces at low temperatures for over 3 weeks. The decay rates of ZEBOV and Reston ebolavirus (REBOV) plus MARV within a dynamic aerosol were calculated. ZEBOV and MARV had similar decay rates, whilst REBOV showed significantly better survival within an aerosol. SIGNIFICANCE AND IMPACT OF THE STUDY: Data on the survival of two ebolaviruses are presented for the first time. Extended data on the survival of MARV are presented. Data from this study extend the knowledge on the survival of filoviruses under different conditions and provide a basis with which to inform risk assessments and manage exposure to filoviruses.

Treatment of murine pneumonic Francisella tularensis infection with gatifloxacin, moxifloxacin or ciprofloxacin.

The efficacies of gatifloxacin and moxifloxacin were assessed in a BALB/c mouse model of pneumonic tularemia and compared with the efficacy of ciprofloxacin. The rate of relapse following dexamethasone treatment was also investigated. Mice were given 100 mg/kg of the antibiotic by oral administration twice daily for 14 days following an aerosol challenge. All three fluoroquinolones prevented disease during the treatment period, but significant failure rates occurred after the cessation of therapy. Both gatifloxacin and moxifloxacin were more effective than ciprofloxacin at reducing late mortality. Fluoroquinolones may therefore be considered useful candidates for the treatment of pneumonic tularemia.

In vivo efficacy of fluoroquinolones against systemic tularaemia infection in mice.

OBJECTIVES: The in vivo efficacy of ciprofloxacin, gatifloxacin and moxifloxacin were assessed in an experimental Francisella tularensis Schu S4 infection in the BALB/c mouse model. METHODS: Mice were given 100 mg/kg of antibiotic by oral administration twice daily commencing at 6, 24 or 48 h post-exposure and continued for 14 days post-exposure. All mice were challenged subcutaneously with 1 x 10(6) cfu F. tularensis Schu S4 and observed for a period of 56 days. RESULTS: Treatment initiated 6 h post-exposure resulted in 94, 100 and 100% survival for ciprofloxacin, gatifloxacin and moxifloxacin, respectively. When treatment was delayed until 24 h post-exposure the survival rates were ciprofloxacin 67%, gatifloxacin 96% and moxifloxacin 100%. Treatment initiated at 48 h post-exposure resulted in a significant reduction in the survival rate of the ciprofloxacin-treated mice, with 0% survival compared with 84 and 62% for gatifloxacin and moxifloxacin, respectively. Non-treated infected control mice died within 96 h post-exposure. Dexamethasone given at day 42 for 7 days to suppress the animals' immune system caused relapse in all of the treatment groups. CONCLUSIONS: Both gatifloxacin and moxifloxacin were more effective at preventing mortality than ciprofloxacin and could be considered as alternative antibiotics in the treatment of systemic F. tularensis infection.

Comparison of gatifloxacin, moxifloxacin and ciprofloxacin for treatment of experimental Burkholderia pseudomallei infection.

OBJECTIVES: To compare the efficacy of moxifloxacin, gatifloxacin and ciprofloxacin for the post-exposure prophylaxis and treatment of experimental Burkholderia pseudomallei infection. The presence of persistent infection in treated animals and the rate of relapse following dexamethasone treatment were also investigated. METHODS: BALB/c mice were inoculated subcutaneously with 1.75 x 10(6) cfu of B. pseudomallei strain 576. Gatifloxacin, moxifloxacin and ciprofloxacin (100 mg/kg) were given orally at 12 hourly intervals for 14 days starting at 6 h, 7 days or 12 days post-challenge. Control mice did not receive antibiotic therapy. RESULTS: No regimen gave 100% protection. Prophylaxis was most effective when started 6 h post-challenge, with survival rates at 42 days for ciprofloxacin, gatifloxacin and moxifloxacin being 58%, 75% and 75%, respectively. For treatment started at day 7 post-challenge, survival rates were 17%, 11% and 44%, respectively. When antibiotic treatment was delayed until day 12 post-challenge, survival rates fell to 21%, 17% and 28%, respectively. Following dexamethasone treatment of survivors at 42 days post-challenge, relapses occurred in all treatment groups. CONCLUSIONS: Fluoroquinolones do not provide good post-exposure protection against infection with B. pseudomallei. The newer agents moxifloxacin and gatifloxacin are not significantly better than ciprofloxacin for this purpose.