Environmental and Demographic Determinants of Avian Influenza Viruses in Waterfowl across the Contiguous United States

Outbreaks of avian influenza in North American poultry have been linked to wild waterfowl. A first step towards understanding where and when avian influenza viruses might emerge from North American waterfowl is to identify environmental and demographic determinants of infection in their populations. Laboratory studies indicate water temperature as one determinant of environmental viral persistence and we explored this hypothesis at the landscape scale. We also hypothesized that the interval apparent prevalence in ducks within a local watershed during the overwintering season would influence infection probabilities during the following breeding season within the same local watershed. Using avian influenza virus surveillance data collected from 19,965 wild waterfowl across the contiguous United States between October 2006 and September 2009 We fit Logistic regression models relating the infection status of individual birds sampled on their breeding grounds to demographic characteristics, temperature, and interval apparent prevalence during the preceding overwintering season at the local watershed scale. We found strong support for sex, age, and species differences in the probability an individual duck tested positive for avian influenza virus. In addition, we found that for every seven days the local minimum temperature fell below zero, the chance an individual would test positive for avian influenza virus increased by 5.9 percent. We also found a twelve percent increase in the chance an individual would test positive during the breeding season for every ten percent increase in the interval apparent prevalence during the prior overwintering season. These results suggest that viral deposition in water and sub-freezing temperatures during the overwintering season may act as determinants of individual level infection risk during the subsequent breeding season. Our findings have implications for future surveillance activities in waterfowl and domestic poultry populations. Further study is needed to identify how these drivers might interact with other host-specific infection determinants, such as species phylogeny, immunological status, and behavioral characteristics

Differential effects of Toremifene on Doxorubicin, Vinblastine and Tc-99m-sestamibi in P-glycoprotein-expressing Breast and Head and Neck Cancer cell lines

The effect of toremifene on P-glycoprotein-mediated multidrug resistance (MDR) in breast and head and neck cancer cell lines was measured in vitro and in vivo. Pgp expression was low and high, respectively, in drug-sensitive (MCF7-S, KB) and drug-resistant (MCF7-R, MCF7-R1, KBV1) cell lines. Toremifene (7.5 μM) significantly enhanced cytoplasmic and nuclear accumulation of doxorubicin in drug-resistant cells. Toremifene (10 μM) increased the in vitro cytotoxicity of doxorubicin in drug-resistant breast cancer cells (13-fold and 21-fold for MCF7-R and MCF7-R1, respectively) without affecting the sensitivity of MCF7-S cells. Similarly, toremifene (10 μM) caused a 12-fold increase in the sensitivity of KBV1 cells to vinblastine. In contrast, toremifene (5 μM) reduced the net uptake of the radiolabelled Pgp substrate, Tc-99m-sestamibi, in the Pgp-overexpressing cell lines by factors of 0.32 and 0.42 for MCF7-R1 and KBV1 cells, respectively (p\u3c0.01), and, to a lesser extent, by corresponding factors of 0.89 and 0.86 in the drug-sensitive cell lines (p\u3c0.05 and p\u3e0.05, respectively). In nude mice bearing both KB and KBV1 xenograft tumours, significantly higher tumour levels of Tc-99m-sestamibi were recorded in KB tumours compared with KBV1 tumours. After 3 days of treatment with intraperitoneal toremifene (25 mg/kg), tumour levels of Tc-99m-sestamibi were reduced in KB and KBV1 tumours but only statistically significantly for KB tumours. Toremifene is a potent MDR modulating agent with respect to chemotherapeutic agents but has the opposite effect with respect to Tc-99m-sestamibi. This finding is of importance in view of the widespread use of Tc-99m-sestamibi as an imaging surrogate for a chemotherapeutic agent