Publications

AIMS

To test the efficacy of the Tobacco Status Project (TSP) Facebook smoking cessation intervention for young adults relative to referral to an on-line program on biochemically verified 7-day abstinence from smoking.

DESIGN

Two-group parallel randomized controlled trial, comparing TSP (n = 251) to on-line control (n = 249) with follow-up to 12 months.

SETTING

On-line, throughout the United States.

PARTICIPANTS

Young adult cigarette smokers (mean age 21 years; 73% white, 55% female, 87% daily smokers).

INTERVENTIONS AND COMPARATOR

TSP provided private Facebook groups tailored to stage of change to quit smoking, daily contacts, weekly live counseling sessions, and for those ready to quit, six cognitive behavioral therapy counseling sessions. Some TSP groups were assigned randomly to receive a monetary incentive for engagement. Control provided referral to the National Cancer Institute Smokefree.gov website.

MEASUREMENTS

PRIMARY OUTCOME: Biochemically verified 7-day abstinence over 12 months.

SECONDARY OUTCOMES

Post-treatment (3-month) abstinence; reported abstinence, quit attempt, reduction in smoking, readiness to quit smoking over 12 months.

FINDINGS

Verified 7-day abstinence was not significantly different for intervention compared with control over 1 year: month 3 (8.3 versus 3.2%), 6 (6.2 versus 6.0%), and 12 (5.9 versus 10.0%); odds ratio (OR) = 1.07; 95% confidence interval (CI) = 0.23, 4.97; retention = 71%. There was an effect at 3 months (OR = 2.52; CI = 1.56, 4.04; P < 0.0001). There were no 12-month treatment effects for reported abstinence (P = 0.746), reduction in smoking by 50% or more (P = 0.533), likelihood of having made a quit attempt (P = 0.387) or stage of change over time (0.968). Participants in TSP engaged more and rated the intervention more favorably than those in the control condition.

CONCLUSIONS

Compared with referral to a smoking cessation website, a novel USA-focused Facebook smoking cessation intervention did not improve abstinence from smoking over 1 year, but increased abstinence at the end of treatment and was engaging to participants.

Although extensive work has delineated many of the mechanisms of extracellular matrix (ECM) production, far less is known about pathways that regulate ECM degradation. This is particularly true of cellular internalization and degradation of matrix, which play an underappreciated role in ECM metabolism and lung fibrosis. For example, genetic perturbation of this pathway leads to exacerbated fibrosis in experimental animal models. In this work, we present the results of an unbiased screen of Drosophila phagocytes that yielded multiple genes that when silenced led to increased collagen uptake. We further describe the function of Cell Division Cycle 7-Kinase (CDC7) as a specific suppressor of collagen uptake. We show that the genetic or pharmacologic inhibition of CDC7 results in increased expression of the collagen endocytic receptor Endo180. Chromobox 5 (CBX5) is a putative target of CDC7 and genetic silencing of CBX5 also results in increased Endo180 and collagen uptake. Finally, CRISPR-mediated activation of Endo180 expression results in increased collagen uptake, suggesting that CDC7 regulates collagen internalization through increased Endo180 expression. Targeting the regulatory elements of the collagen degradative machinery may be a useful therapeutic approach in diseases of fibrosis or malignancy.

Hodgkin lymphoma treatment continues to evolve as new means of assessing response to treatment, new appreciation of important risk factors, and more effective therapeutic agents become available. Treatment algorithms integrating functional imaging now provide the opportunity to modify therapy during its delivery, allowing adjustment of duration and intensity of chemotherapy and rationale identification of patients who may benefit from the addition of therapeutic irradiation. Novel agents, including the antibody drug conjugate brentuximab vedotin and checkpoint inhibitors such as nivolumab and pembrolizumab can improve the effectiveness of treatment while keeping toxicity within acceptable limits. Carefully designed clinical trials permit the identification of superior approaches in which efficacy is enhanced and toxicity minimized. Clinicians treating patients with Hodgkin lymphoma now have access to novel treatment approaches, which will require detailed assessment of each patient and careful discussion of the goals and risks of treatment at the time of planning primary treatment, again during delivery of that treatment as data indicating ongoing effectiveness become available, at the conclusion of initial intervention, and, when the need arises, at the time of recurrence of disease.

The small intestinal tuft cell-ILC2 circuit mediates epithelial responses to intestinal helminths and protists by tuft cell chemosensory-like sensing and IL-25-mediated activation of lamina propria ILC2s. Small intestine ILC2s constitutively express the IL-25 receptor, which is negatively regulated by A20 (Tnfaip3). A20 deficiency in ILC2s spontaneously triggers the circuit and, unexpectedly, promotes adaptive small-intestinal lengthening and remodeling. Circuit activation occurs upon weaning and is enabled by dietary polysaccharides that render mice permissive for Tritrichomonas colonization, resulting in luminal accumulation of acetate and succinate, metabolites of the protist hydrogenosome. Tuft cells express GPR91, the succinate receptor, and dietary succinate, but not acetate, activates ILC2s via a tuft-, TRPM5-, and IL-25-dependent pathway. Also induced by parasitic helminths, circuit activation and small intestinal remodeling impairs infestation by new helminths, consistent with the phenomenon of concomitant immunity. We describe a metabolic sensing circuit that may have evolved to facilitate mutualistic responses to luminal pathosymbionts.