Dysregulation of Cytokine Response in Canadian First Nations Communities: Is There an Association with Persistent Organic Pollutant Levels?

In vitro and animal studies report that some persistent organic pollutants (POPs) trigger the secretion of proinflammatory cytokines. Whether POP exposure is associated with a dysregulation of cytokine response remains to be investigated in humans. We studied the strength of association between plasma POP levels and circulating cytokines as immune activation markers. Plasma levels of fourteen POPs and thirteen cytokines were measured in 39 Caucasians from a comparator sample in Québec City (Canada) and 72 First Nations individuals from two northern communities of Ontario (Canada). Caucasians showed significantly higher levels of organochlorine insecticides (β-HCH, p,p′-DDE and HCB) compared to First Nations. Conversely, First Nations showed higher levels of Mirex, Aroclor 1260, PCB 153, PCB 170, PCB 180 and PCB 187 compared to Caucasians. While there was no difference in cytokine levels of IL-4, IL-6, IL-10 and IL-22 between groups, First Nations had significantly greater average levels of IFNγ, IL-1β, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFα and TNFβ levels compared to Caucasians. Among candidate predictor variables (age, body mass index, insulin resistance and POP levels), high levels of PCBs were the only predictor accounting for a small but significant effect of observed variance (∼7%) in cytokine levels. Overall, a weak but significant association is detected between persistent organochlorine pollutant exposure and elevated cytokine levels. This finding augments the already existing information that environmental pollution is related to inflammation, a common feature of several metabolic disorders that are known to be especially prevalent in Canada's remote First Nations communities

In Vivo Comparison of Two Human Norovirus Surrogates for Testing Ethanol-Based Handrubs: The Mouse Chasing the Cat!

Human noroviruses (HuNoV), a major cause of acute gastroenteritis worldwide, cannot be readily cultured in the lab. Therefore, a feline calicivirus (FCV) is often used as its surrogate to, among other things, test alcohol-based handrubs (ABHR). The more recent laboratory culture of a mouse norovirus (MNV) provides an alternative. While MNV is closer to HuNoV in several respects, to date, no comparative testing of FCV and MNV survival and inactivation on human hands has been performed. This study was designed to address the knowledge gap. The rates of loss in viability during drying on hands were −1.91 and −1.65% per minute for FCV and MNV, respectively. When the contaminated skin was exposed for 20 s to either a commercial ABHR with 62% (v/v) ethanol or to 75% (v/v) ethanol in water, FCV infectivity was reduced by <1 log10 while that of MNV by nearly 2.8 log10. Extending the contact time to 30 s reduced the FCV titer by almost 2 log10 by both test substances and that of MNV by >3.5 log10 by the commercial ABHR while 75% ethanol did not show any noticeable improvement in activity as compared to the 20 s contact. An 80% (v/v) aqueous solution of ethanol gave only a 1.75 log10 reduction in MNV activity after 20 s. The results show significant differences in the ethanol susceptibility of FCV and MNV in contact times relevant to field use of ABHR and also that 62% ethanol was a more effective virucide than either 75% or 80% ethanol. These findings indicate the need for a review of the continuing use of FCV as a surrogate for HuNoV

Learning From History To Increase Positive Public Reception and Social Value Alignment of Evidence-Based Science Communication

For effective science communication, three general objectives should be taken into consideration: 1) accurate conveyance of the scientific evidence; 2) warm public reception of the communicator; and 3) alignment of the information with social values. An examination of both successful and failed science communication efforts over the course of history can reveal strategies to better meet these objectives. This article looks back at influential moments of science communication over the past two millennia in the context of the objectives and, using lessons learned from these events as a guide, introduces a five-element approach to improve the potential for attaining the objectives

Reduction in the viability of FCV and MNV after contact with ethanol.

<p>Virus reduction was observed after 20 s (A) or 30 s (B) contact time with a commercial ABHR (62% ethanol) and an aqueous solution of 75% (v/v) ethanol on the fingerpads of adult subjects (n = 6). Significant difference between FCV and MNV (p<0.01) indicated by asterisks.</p

Reduction of MNV after 20 second contact with ethanol.

<p>MNV reduction was observed after 20 s contact time with one of either a commercial ABHR (62% ethanol), 75% ethanol or 80% aqueous ethanol solution on the fingerpads of adult subjects (n = 6). Significant differences were observed between both 62% and 75% (p<0.01) and 80% (p<0.01) indicated by asterisks (*). A significant difference was also seen between 75% and 80% (p<0.01) indicated by the double dagger (‡).</p

Ultrasensitive Norovirus Detection Using DNA Aptasensor Technology

<div><p>DNA aptamers were developed against murine norovirus (MNV) using SELEX (Systematic Evolution of Ligands by EXponential enrichment). Nine rounds of SELEX led to the discovery of AG3, a promising aptamer with very high affinity for MNV as well as for lab-synthesized capsids of a common human norovirus (HuNoV) outbreak strain (GII.3). Using fluorescence anisotropy, AG3 was found to bind with MNV with affinity in the low picomolar range. The aptamer could cross-react with HuNoV though it was selected against MNV. As compared to a non-specific DNA control sequence, the norovirus-binding affinity of AG3 was about a million-fold higher. In further tests, the aptamer also showed nearly a million-fold higher affinity for the noroviruses than for the feline calicivirus (FCV), a virus similar in size and structure to noroviruses. AG3 was incorporated into a simple electrochemical sensor using a gold nanoparticle-modified screen-printed carbon electrode (GNPs-SPCE). The aptasensor could detect MNV with a limit of detection of approximately 180 virus particles, for possible on-site applications. The lead aptamer candidate and the aptasensor platform show promise for the rapid detection and identification of noroviruses in environmental and clinical samples.</p></div

Binding assays.

<p>A) Binding affinity measurements for 5′-fluorescein-modified AG3 with MNV using a polycarbonate filter binding assay (diamonds) and a fluorescence anisotropy assay (triangles). The binding affinity of 5′-fluorescein tagged AG3 to FCV (circles) as well as a non-specific DNA control with MNV (squares) were also measured by anisotropy. Measurements are fitted using either the Hill or Logistic functions (solid lines). Inset: Much higher concentrations of virus are required in order to show any anisotropy change in the controls. B) Fluorescence anisotropy results from binding of 5′-fluorescein-modified AG3 with varying concentrations of GII.3 HuNoV capsid.</p