Publications

BACKGROUND

Graphic warning labels are a tobacco control best practice that is mandated in the US for cigarettes under the 2009 Family Smoking Prevention and Tobacco Control Act. However, smokeless tobacco products are not required to carry graphic warning labels, and as of September 2014, electronic cigarettes in the US carry no warning labels and are aggressively marketed, including with "reduced harm" or "FDA Approved" messages.

METHODS

In this online experiment, 483 US adult non-users of tobacco were randomized to view print advertisements for moist snuff, snus, and e-cigarettes with either warning labels (current warning label, graphic warning label) or "endorsements" (a "lower risk" label proposed by a tobacco company, an "FDA Approved" label) or control (tobacco advertisement with no label, advertisement for a non-tobacco consumer products). Main outcome measures included changes in perceived harm, positive attitudes towards, openness to using, and interest in a free sample of moist snuff, snus, and e-cigarettes.

RESULTS

The graphic warning label increased perceived harm of moist snuff and e-cigarettes. "Lower risk" and "FDA Approved" labels decreased perceived harm of moist snuff and snus respectively. Current warning label and graphic warning label significantly lowered positive attitudes towards e-cigarettes. In this sample of non-users of tobacco, 15% were interested in a free sample of alternative tobacco products (predominantly e-cigarettes). Proportion of participants interested in a free sample did not differ significantly across the conditions, but those interested in a free sample had significantly lower perceptions of harm of corresponding tobacco products.

CONCLUSIONS

Regulatory agencies should not allow "lower risk" warning labels, which have similar effects to the "FDA Approved" label, which is prohibited, and should consider implementing graphic warning labels for smokeless tobacco products and e-cigarettes.

UNLABELLED

The full-length isoform of matrixmetalloproteinase-2 (FL-MMP-2) plays a role in turnover of the cardiac extracellular matrix. FL-MMP-2 is also present intracellularly in association with sarcomeres and, in the setting of oxidative stress, cleaves myofilament proteins with resultant impaired contractility. Recently, a novel N-terminal truncated MMP-2 isoform (NTT-MMP-2) generated during oxidative stress was identified and shown to induce severe systolic failure; however, the injury mechanisms remained unclear. In this study, cardiac-specific NTT-MMP-2 transgenic mice were used to determine the physiological effects of NTT-MMP-2 on: force development of intact myocardium; the function of cardiac myofilaments in demembranated myocardium; and on intracellular Ca(2+) transients in isolated myocytes. We related the contractile defects arising from NTT-MMP-2 expression to the known intracellular locations of NTT-MMP-2 determined using immunohistochemistry. Comparison was made with the pathophysiology arising from cardiac-specific FL-MMP-2 transgenic mice. Consistent with previous studies, FL-MMP-2 was localized to myofilaments, while NTT-MMP-2 was concentrated within subsarcolemmal mitochondria and to sites in register with the Z-line. NTT-MMP-2 expression caused a 50% reduction of force development by intact myocardium. However, NTT-MMP-2 expression did not reduce myofilament force development, consistent with the lack of NTT-MMP-2 localization to myofilaments. NTT-MMP-2 expression caused a 50% reduction in the amplitude of Ca(2+) transients, indicating impaired activation.

CONCLUSIONS

Unlike FL-MMP-2, NTT-MMP-2 does not mediate myofilament damage. Instead, NTT-MMP-2 causes impaired myocyte activation, which may involve effects due to localization in mitochondria and/or to transverse tubules affecting Ca(2+) transients. Thus, FL-MMP-2 and NTT-MMP-2 have discrete intracellular locations and mediate different intracellular damage to cardiac myocytes.

Delayed recovery from surgery causes personal suffering and substantial societal and economic costs. Whether immune mechanisms determine recovery after surgical trauma remains ill-defined. Single-cell mass cytometry was applied to serial whole-blood samples from 32 patients undergoing hip replacement to comprehensively characterize the phenotypic and functional immune response to surgical trauma. The simultaneous analysis of 14,000 phosphorylation events in precisely phenotyped immune cell subsets revealed uniform signaling responses among patients, demarcating a surgical immune signature. When regressed against clinical parameters of surgical recovery, including functional impairment and pain, strong correlations were found with STAT3 (signal transducer and activator of transcription), CREB (adenosine 3',5'-monophosphate response element-binding protein), and NF-κB (nuclear factor κB) signaling responses in subsets of CD14(+) monocytes (R = 0.7 to 0.8, false discovery rate <0.01). These sentinel results demonstrate the capacity of mass cytometry to survey the human immune system in a relevant clinical context. The mechanistically derived immune correlates point to diagnostic signatures, and potential therapeutic targets, that could postoperatively improve patient recovery.