Evidence for discrete stages of human natural killer cell differentiation in vivo

Human natural killer (NK) cells originate from CD34(+) hematopoietic progenitor cells, but the discrete stages of NK cell differentiation in vivo have not been elucidated. We identify and functionally characterize, from human lymph nodes and tonsils, four NK cell developmental intermediates spanning the continuum of differentiation from a CD34(+) NK cell progenitor to a functionally mature NK cell. Analyses of each intermediate stage for CD34, CD117, and CD94 cell surface expression, lineage differentiation potentials, capacity for cytokine production and natural cytotoxicity, and ETS-1, GATA-3, and T-BET expression provide evidence for a new model of human NK cell differentiation in secondary lymphoid tissues

Measuring cervical cancer risk: development and validation of the CARE Risky Sexual Behavior Index

To develop and validate a risky sexual behavior index specific to cervical cancer research

Cancer Screening Practices Among Amish and Non-Amish Adults Living in Ohio Appalachia

The Amish, a unique community living in Ohio Appalachia, have lower cancer incidence rates than non-Amish living in Ohio Appalachia. The purpose of this study was to examine cancer screening rates among Amish compared to non-Amish adults living in Ohio Appalachia and a national sample of adults of the same race and ethnicity in an effort to explain cancer patterns

The PP2A inhibitor SET regulates natural killer cell IFN-γ production

Monokines (i.e., interleukin [IL]-12, -18, and -15) induce natural killer (NK) cells to produce interferon-γ (IFN-γ), which is a critical factor for immune surveillance of cancer and monocyte clearance of infection. We show that SET, which is a potent inhibitor of protein phosphatase type 2A (PP2A) activity, is highly expressed in human CD56bright NK cells, which produce more IFN-γ than CD56dim NK cells. SET was up-regulated upon monokine stimulation of primary human NK cells. Furthermore, ectopic overexpression of SET significantly enhanced IFN-γ gene expression in monokine-stimulated NK cells. In contrast, RNAi-mediated suppression of SET expression renders NK cells inefficient in producing high levels of IFN-γ in response to monokine costimulation. Mechanistically, suppression of PP2A activity by SET is important for IFN-γ gene expression in NK cells. In fact, treatment of primary human NK cells with the PP2A activator 1,9-dideoxy-forskolin, as well as administration of the drug to C57BL/6 mice, significantly reduced NK-dependent IFN-γ production in response to monokine treatment. Further, SET knockdown or pharmacologic activation of PP2A diminished extracellular signal-regulated kinase 1/2, p65RelA, signal transducer and activator of transduction 4 (STAT4), and STAT5 activity in monokine-stimulated NK cells, potentially contributing to the reduction in IFN-γ gene expression. Thus, SET expression is essential for suppressing PP2A phosphatase activity that would otherwise limit NK cell antitumoral and/or antiinflammatory functions by impairing NK cell production of IFN-γ

A Cluster Randomized Controlled Trial for a Multi-Level, Clinic-Based Smoking Cessation Program with Women in Appalachian Communities: Study Protocol for the Break Free Program

BACKGROUND: The cervical cancer burden is high among women living in Appalachia. Cigarette smoking, a cervical cancer risk factor, is also highly prevalent in this population. This project aims to increase smoking cessation among women living in Appalachia by embedding a smoking cessation program within a larger, integrated cervical cancer prevention program. METHODS: The broader program, the Take CARE study, is a multi-site research collaborative designed to address three risk factors for cervical cancer incidence and mortality: tobacco use, human papillomavirus (HPV) infection, and cervical cancer screening. Break Free is a primary care clinic-based implementation program that aims to promote smoking cessation among female smokers in Appalachia by standardizing clinical practice protocols. Break Free includes: (1) implementation of a tobacco user identification system in the Electronic Health Record, (2) clinic staff and provider training on the Ask, Advise and Refer (AAR) model, (3) provider implementation of AAR to identify and treat women who want to quit smoking within the next 6 months, (4) facilitated access to cessation phone counseling plus pharmacotherapy, and (5) the bundling of Break Free tobacco cessation with HPV vaccination and cervical cancer screening interventions in an integrated approach to cervical cancer prevention. The study spans 35 Appalachian health clinics across 10 healthcare systems. We aim to enroll 51 adult female smokers per health system (total N = 510). Baseline and follow-up data will be obtained from participant (provider and patient) surveys. The primary outcome is self-reported 12-month point prevalence abstinence among enrolled patients. All randomized patients are asked to complete follow-up surveys, regardless of whether they participated in tobacco treatment. Data analysis of the primary aims will follow intent-to-treat methodology. Secondary outcomes will assess program implementation and cost effectiveness. DISCUSSION: Addressing high tobacco use rates is critical for reducing cervical cancer morbidity and mortality among women living in Appalachia. This study evaluates the implementation and effectiveness of a smoking cessation program in increasing smoking cessation among female smokers. If results demonstrate effectiveness and sustainability, implementation of this program into other health care clinics could reduce both rates of smoking and cervical cancer. Trial registration NCT04340531 (April 9, 2020)

Secondhand Smoke Exposure, Indoor Smoking Bans and Smoking-Related Knowledge in China

Although previous studies have provided strong evidence that Chinese individuals are exposed to secondhand smoke (SHS) and lack knowledge of its harmful effects, there has not been an in-depth exploration of the variability in exposure and knowledge by geographic region, occupation, and socioeconomic status. The objectives of this study were to examine: (1) the demographic factors associated with the level of knowledge of the harmful effects of smoking; (2) the factors related to implementation of in-home and workplace smoking bans; and (3) geographic differences in being exposed to SHS in government buildings, healthcare facilities, restaurants, public transportations, and schools. We used data from the 2010 Global Adult Tobacco Survey-China. Chi-square tests were used for statistical analysis. The results suggested that among Chinese citizens age 15 years and older, there is poor knowledge of the harmful effects of tobacco, and knowledge varies with region and socioeconomic status. Over three-quarters of the households had no smoking restrictions, and a large percentage of workers reported working in places with no smoking ban. In public places, exposure to SHS was high, particularly in rural areas and in the Southwest. These results suggest Chinese individuals are not well informed of smoking and SHS associated risks and are regularly exposed to SHS at home, work and public places

Lebanese medical students’ intention to deliver smoking cessation advice

Objectives: Objectives of this study were to examine the constructs of the Theory of Planned Behavior and determine how they predict Lebanese medical students’ behavioral intention to advise patients to quit smoking. Study design: This was a cross-sectional study conducted among 191 medical students from six medical schools in Lebanon. Methods: The instrument contained scales that measured attitudes toward the behavior, behavioral beliefs, subjective norms, and perceived behavioral control. Psychometric properties of the scale were examined. Item to total scale score correlations were determined and linear regression was conducted to predict the intention to advise smokers to quit. Results: Respondents had a positive, but not very high, intention to deliver smoking cessation advice. Students reported a positive attitude toward advising patients to quit cigarette smoking and a strong belief in the physician’s obligations in smoking cessation advising. The majority reported lack of time to provide smoking cessation advice, insufficient knowledge of pharmacological aids, and the lack of openness of the patient to receive the advice. The attitude scale was the only variable that yielded a significant prediction of the intended behavior. Conclusions: The construct of attitude toward the behavior appeared to be the most predictive of the intention to deliver advice to quit smoking among Lebanese medical students. Focusing training efforts on this construct could improve the rate of delivery of brief cessation counseling