Associations of pre-diagnosis physical activity with treatment tolerance and treatment efficacy in breast cancer patients with neoadjuvant chemotherapy.

PURPOSE: Higher pre-diagnosis physical activity (PA) is associated with lower all-cause mortality in breast cancer (BCa) patients. However, the association with pathological complete response (pCR) is unclear. We investigated the association between pre-diagnosis PA level and chemotherapy completion, dose delay, and pCR in BCa patients receiving neoadjuvant chemotherapy (NACT). METHODS: 180 stage I-III BCa patients receiving NACT (mean [SD] age of diagnosis: 60.8 [8.8] years) in the Sister Study were included. Self-reported recreational and total PA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). The pCR was defined as no invasive or in situ residual in breast or lymph node (ypT0 ypN0). Multivariable logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) for treatment outcomes. RESULTS: In this sample, 45 (25.0%) BCa patients achieved pCR. Higher pre-diagnosis recreational PA was not associated with lower likelihood of chemotherapy completion (highest vs. lowest tertile: OR = 0.87, 95% CI = 0.30-2.56; Ptrend = 0.84), greater dose delay (OR = 1.45, 95% CI = 0.54-3.92; Ptrend = 0.46), or greater odds of pCR (OR = 1.28, 95% CI = 0.49-3.34; Ptrend = 0.44). Associations were similar for pre-diagnosis total PA. Meeting the recommended level of recreational PA was not associated with pCR overall (≥ 7.5 vs. < 7.5 MET-hrs/wk: OR = 1.33, 95% CI = 0.59-3.01). CONCLUSIONS: Although small sample size and limited information on exercise closer to time of diagnosis limit interpretation, pre-diagnosis PA was not convincingly associated with treatment tolerance or treatment efficacy in BCa patients receiving NACT. Future investigations are needed to better understand the impact of pre-diagnosis PA on BCa treatment.

Smoking, Lung Cancer Stage, and Prognostic Factors-Findings from the National Lung Screening Trial.

BACKGROUND: Low-dose computed tomography (LDCT) increases the early detection of lung cancer. Identifying modifiable behaviors that may affect tumor progression in LDCT-detected patients increases the likelihood of long-term survival and a good quality of life. METHODS: We examined cigarette smoking behaviors on lung cancer stage, progression, and survival in 299 ever-smoking patients with low-dose CT-detected tumors from the National Lung Screening Trial. Univariate and multivariate Cox models were used to estimate the hazard ratio (HR) for smoking variables on survival time. RESULTS: Current vs. former smokers and early morning smokers (≤5 min after waking, i.e., time to first cigarette (TTFC) ≤ 5 min) had more advanced-stage lung cancer. The adjusted HR for current vs. former smokers was 1.3 (95% confidence interval [CI] 0.911-1.98, p = 0.136) for overall survival (OS) and 1.3 (0.893-1.87, p = 0.1736) for progression-free survival (PFS). The univariate hazard ratios for TTFC ≤ 5 min vs. >5 min were 1.56 (1.1-2.2, p = 0.013) for OS and 1.53 (1.1-2.12, p = 0.01) for PFS. Among current smokers, the corresponding HRs for early TTFC were 1.78 (1.16-2.74, p = 0.0088) and 1.95 (1.29-2.95, p = 0.0016) for OS and PFS, respectively. In causal mediation analysis, the TTFC effect on survival time was mediated entirely through lung cancer stage. CONCLUSION: The current findings indicate smoking behaviors at diagnosis may affect lung cancer stage and prognosis.

Berry Consumption in Relation to Allostatic Load in US Adults: The National Health and Nutrition Examination Survey, 2003-2010.

INTRODUCTION: Berries are a rich source of antioxidant polyphenols and other nutrients that are associated with good health. Allostatic load (AL) is an aggregate measure of chronic stress-induced physiological dysregulations across cardiovascular, metabolic, autonomic, and immune systems; the extent of these dysregulations, collectively or in each system, can be characterized by a composite score or a domain score assessed by integrated biomarkers. It was hypothesized that the anti-inflammatory and other effects of berries lower AL. The association was determined between berry consumption and AL composite and domain scores in the 2003-2010 National Health and Nutrition Examination Survey (NHANES). METHODS: Berry intake was measured using two 24 h dietary recalls collected from US adults in the 2003-2010 NHANES (n = 7684). The association with AL and its specific domains was examined using population weight-adjusted multivariable linear regression. RESULTS: The mean AL composite scores for consumers of any berries (11.9), strawberries (11.6), and blueberries (11.6), respectively, were significantly lower than nonconsumers (12.3), after fully adjusting for sociodemographic, lifestyle, and dietary confounders. A significant dose-response relationship was determined between greater consumption of total berries, strawberries, and blueberries and lower mean AL composite scores (p-trend < 0.05, for all). Consistently, mean cardiovascular and metabolic domain scores remained significantly lower in the consumers of total berries (mean cardiovascular domain score: 4.73 versus 4.97 for nonconsumers; mean metabolic domain score: 2.97 versus 3.1), strawberries (4.73 versus 4.95; 2.99 versus 3.1), and blueberries (4.6 versus 4.95; 2.92 versus 3.11). Berry consumers also had significantly lower mean AL immune scores (1.52 versus 1.56) and lower mean AL autonomic scores (2.49 versus 2.57) than nonconsumers (initial sample: n = 15,620). CONCLUSIONS: The current study indicates that consumption of berries lowers the AL composite scores and potentially reduces stress-related disease risks in the US adult population.

The Epidemiology of Berry Consumption and Association of Berry Consumption with Diet Quality and Cardiometabolic Risk Factors in United States Adults: The National Health and Nutrition Examination Survey, 2003-2018.

BACKGROUND: Berries are rich in important nutrients and bioactive compounds, which could potentially contribute to maintenance of normal lipid and glucose profiles. OBJECTIVE: We reported the epidemiology of berry consumption and examined associations of berry consumption with diet quality [measured by Healthy Eating Index (HEI-2015)] and levels of cardiometabolic risk factors, including body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), glycated hemoglobin, and fasting biomarkers: triglycerides, low-density lipoprotein cholesterol (LDL cholesterol), glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: We evaluated 33,082 adults (aged ≥20 y) using two 24-h diet recalls from National Health and Nutrition Examination Survey (2003-2018). Multivariable linear regression models were applied to examine the associations of total and individual berry intake with diet quality and cardiometabolic risk factors using appropriate sample weights. RESULTS: Approximately 25 % of the United States adults consumed berries (0.08 ± 0.003 cup-equivalents/d), representing ∼10 % of the daily mean total fruit intake. Among berry consumers, the mean intake of strawberries (0.31 ± 0.01 cup-equivalents) was higher than for other berries. Berry consumers had a significantly higher HEI-2015 score than nonconsumers (mean HEI-2015 score = 58.8 compared with 52.3, P < 0.0001). Berry consumers had significantly lower concentrations of cardiometabolic indices than nonconsumers, including BMI, WC, SBP, total cholesterol, LDL cholesterol, triglycerides, fasting insulin, HOMA-IR, and higher mean HDL cholesterol, after adjusting for sociodemographic, lifestyle, and dietary confounders (all P < 0.05). CONCLUSIONS: United States adult berry consumers had a higher diet quality and lower concentrations of cardiometabolic risk factors, suggesting a favorable role for berries in diets and cardiometabolic disease prevention in United States adult population.

Consumption of Berries and Flavonoids in Relation to Mortality in NHANES, 1999-2014.

BACKGROUND: Berries are foods that are abundant in nutrients, especially flavonoids, that promote good health; however, the effects of total berries on mortality are not well characterized. OBJECTIVES: We evaluated whether intakes of total berries and specific berry types including blueberries, strawberries, cranberries, flavonoids, and subclasses of flavonoids (anthocyanidins, flavonols, flavones, flavanones, flavan-3-ols, and isoflavones) in relation to mortality risk in United States adults. METHODS: A nationally representative sample of the United States adult population was obtained using data from the 1994-2014 NHANES (n = 37,232). Intake of berries was estimated using 24-h food recalls (1999-2014), and flavonoids intake was calculated using the matched USDA's expanded flavonoid database. Mortality outcomes based on 8 y of follow-up were obtained using linked death certificates. RESULTS: Compared with nonconsumers, the multivariable-adjusted hazard ratio for all-cause mortality was 0.79 [95% confidence intervals (CI): 0.7, 0.89] for any berry consumption, 0.86 (0.75, 0.99) for strawberry consumption 0.79 (0.66, 0.95) for blueberries, and 0.69 (0.51, 0.93) for cranberries. Compared with the lower median of intake, risk of all-cause mortality for greater intake was 0.85 (0.74, 0.97) for total flavonoids, 0.85 (0.76, 0.95) for anthocyanidins, 0.9 (0.82, 0.99) for flavan-3-ols, 0.89 (0.79, 0.9) for flavanols, and 0.89 (0.8, 0.99) for flavones. There was a dose-response relationship between intakes of total flavonoids, anthocyanidins, and flavones and lower all-cause mortality risks (Ptrend < 0.05). Risk for cardiometabolic mortality was 0.75 (0.58, 0.98) for berry consumers and 0.49 (0.25, 0.98) for cranberry consumers. For respiratory disease mortality, risk was 0.41 (0.2, 0.86), compared with blueberry nonconsumers. CONCLUSION: Higher intakes of berries and flavonoids were associated with a lower overall mortality risk in adult Americans. Few adults regularly consume berries, indicating that increased intake of berries and flavonoid-rich foods may be beneficial to health.

Berry Consumption and Sleep in the Adult US General Population: Results from the National Health and Nutrition Examination Survey 2005-2018.

INTRODUCTION: Poor sleep is associated with numerous adverse health outcomes. Berries are rich in micronutrients and antioxidants that may improve sleep quality and duration. We determined the association of berry consumption and sleep duration and sleep difficulty among adult participants in NHANES. METHODS: We analyzed the diet of US adults aged ≥ 20 y using two non-consecutive 24 h recalls from the National Health and Nutrition Examination Survey 2005 to 2018 (N = 29,217). Poor sleep quality was measured by sleep duration (short sleep duration: <7 h), long sleep (≥9 h), and reported sleep difficulty. The relative risk of poor sleep outcomes for berry consumers vs. nonconsumers was modelled using population weight-adjusted multivariable general logistic regression. RESULTS: About 46% of participants reported inadequate sleep duration, and 27% reported sleep difficulties. Twenty-two percent reported consuming berries. Berry consumers had a 10-17% decreased risk of short sleep. The findings were consistent for specific berry types including strawberries and blueberries (p < 0.05). No significant associations with long sleep were found for total berries and any berry types. A decreased risk of sleep difficulties was found to be linked to blackberry consumption (adjusted OR = 0.63, 95% CI: 0.40-0.97; p = 0.036) but not for other berries. CONCLUSIONS: US adult berry consumers had a decreased risk of reporting short sleep compared to nonconsumers. Berries are underconsumed foods in the US adult population, and increased berry consumption may improve sleep quality.

Associations Between Leisure-Time Physical Activity Level and Peripheral Immune Cell Populations in the US General Population, Analysis of the National Health and Nutrition Examination Survey Data, 1999-2018.

BACKGROUND: Chronic levels of inflammation are associated with higher risk of many chronic diseases. Physical activity (PA) lowers the risk of cancer, cardiovascular disease (CVD), diabetes and others. One mechanism for PA-induced protection may be through the immune system. We investigated the association between leisure-time PA and peripheral immune cell populations in a large nationally representative sample of the US general population. METHODS: A total of 17,093 participants [mean (SE) age of 41.6 (0.3) years] of the National Health and Nutrition Examination Survey 1999-2018 were included. Self-reported leisure-time PA was converted to metabolic equivalent of task hours per week (MET-hrs/wk). White blood cell (WBC) count, WBC ratios, and platelet count were derived. Multivariable linear regression analyses were used to estimate associations between leisure-time PA level and peripheral immune cell populations. Multivariable logistic regression analyses were used to estimate associations between leisure-time PA and metrics of WBC count and neutrophil-to-lymphocyte ratio (NLR) which may predict mortality. RESULTS: A higher leisure-time PA level was associated with a lower WBC count (> 14.0 vs. < 1.2 MET-hrs/wk adjusted mean (95% confidence interval [CI]): 7.12 (6.86, 7.38) vs. 7.38 (7.12, 7.64) 1000 cells/µL, Ptrend < 0.001) and a lower NLR (> 14.0 vs. < 1.2 MET-hrs/wk adjusted mean (95% CI) 2.04 (1.90, 2.18) vs. 2.13 (1.99, 2.28), Ptrend = 0.007). Leisure-time PA level was not associated with lymphocyte-to-monocyte ratio (LMR; Ptrend = 0.25) or platelet-to-lymphocyte ratio (PLR; Ptrend = 0.69). Compared to the lowest leisure-time PA level (< 1.2 MET-hrs/wk), the highest leisure-time PA level (≥ 14.0 MET-hrs/wk) was associated with a lower probability of a high WBC count (> 8.1 × 109 cells/L; odds ratio [OR] = 0.76, 95% CI = 0.66-0.88) and high NLR (> 2.68; OR = 0.84, 95% CI = 0.72-0.99), which may predict CVD and all-cause mortality. The highest leisure-time PA level also linked to a lower probability of a high WBC count (≥ 8.3 × 109 cells/L; OR = 0.76, 95% CI = 0.66-0.88), which may predict cancer mortality. CONCLUSIONS: We observed an inverse association between leisure-time PA level, WBC count, and NLR, particularly for neutrophil levels. These results suggest that participants at higher levels of leisure-time PA may have lower levels of inflammation, which may be important for future chronic disease outcomes.

Diurnal variability of cortisol in the Pennsylvania adult smoking study: Exploration of association with nicotine intake.

Cortisol in saliva, urine and plasma follows a diurnal rhythm typically characterized as a morning peak and a decline throughout the waking day. While often measured under controlled conditions, inter-individual differences in cortisol diurnal rhythms in free living populations are not well characterized. Cortisol levels may vary substantially between individuals and the level of variation may differ depending on the time of day. Further, associations with individual characteristics such as nicotine dependence on cortisol rhythms have not been adequately determined. We developed a Liquid Chromatography-Tandem Mass Spectrometry method to measure cortisol in saliva of 180 smokers from the Pennsylvania Adult Smoking Study. Diurnal patters of cortisol were determined by obtaining five timed samples throughout the day for a total of 900 determinations. Adherence to the protocol was estimated by asking participants to record the time of sample collection. Longitudinal linear mixed effects models were developed to measure the predictors of mean levels. Phenotypic groups were constructed based on the minimum and maximum cortisol levels. Mixed method modelling was conducted to determine the effects of phenotype and study adherence as well as reported measures of stress, nicotine dependence and cigarette smoking frequency. Nicotine metabolites were measured to accurately quantify dose of smoking intake. Results showed that there was moderate compliance to the timed protocol. Descriptive and analytic findings showed that some smokers had atypical cortisol patterns, and that the cortisol profiles based on experience of maximum and minimum cortisol levels can predict how cortisol varies throughout the day. There was no association with reported stress, cigarettes per day, and nicotine metabolites. There was no association with the Fagerstrom Test for Nicotine Dependence. The Hooked on Nicotine Checklist (HONC) score was associated with decreased cortisol levels. Overall these results show new approaches and expectations to population-based studies of cortisol.

Inhibition of Nicotine Metabolism by Cannabidiol (CBD) and 7-Hydroxycannabidiol (7-OH-CBD).

Cannabis-based products have experienced notable increases in co-usage alongside tobacco products. Several cannabinoids exhibit inhibition of a number of cytochrome P450 (CYP) and UDP glucuronosyltransferase (UGT) enzymes, but few studies have examined their inhibition of enzymes involved in nicotine metabolism. The goal of the present study was to examine potential drug-drug interactions occurring in the nicotine metabolism pathway perpetrated by cannabidiol (CBD) and its active metabolite, 7-hydroxy-CBD (7-OH-CBD). The inhibitory effects of CBD and 7-OH-CBD were tested in microsomes from HEK293 cells overexpressing individual metabolizing enzymes and from human liver tissue. Assays with overexpressing microsomes demonstrated that CBD and 7-OH-CBD inhibited CYP-mediated nicotine metabolism. Binding-corrected IC50,u values for CBD inhibition of nicotine metabolism to cotinine and nornicotine, and cotinine metabolism to trans-3'-hydroxycotinine (3HC), were 0.27 ± 0.060, 0.23 ± 0.14, and 0.21 ± 0.14 µM, respectively, for CYP2A6; and 0.26 ± 0.17 and 0.029 ± 0.0050 µM for cotinine and nornicotine formation, respectively, for CYP2B6. 7-OH-CBD IC50,u values were 0.45 ± 0.18, 0.16 ± 0.08, and 0.78 ± 0.23 µM for cotinine, nornicotine, and 3HC formation, respectively, for CYP2A6, and 1.2 ± 0.44 and 0.11 ± 0.030 µM for cotinine and nornicotine formation, respectively, for CYP2B6. Similar IC50,u values were observed in HLM. Inhibition (IC50,u = 0.37 ± 0.06 µM) of 3HC to 3HC-glucuronide formation by UGT1A9 was demonstrated by CBD. Significant inhibition of nicotine metabolism pathways by CBD and 7-OH-CBD suggests that cannabinoids may inhibit nicotine metabolism, potentially impacting tobacco addiction and cessation.

The effects of reduced nicotine content cigarettes on biomarkers of nicotine and toxicant exposure, smoking behavior and psychiatric symptoms in smokers with mood or anxiety disorders: A double-blind randomized trial.

BACKGROUND: The U.S. Food and Drug Administration and the government of New Zealand have proposed a reduction of the nicotine content in cigarettes to very low levels. This study examined the potential effects of this regulation in smokers with affective disorders. METHODS: In a randomized controlled parallel group trial conducted at two sites in the USA (Penn State University, Hershey, PA and Massachusetts General Hospital, Boston, MA) 188 adult smokers with a current (n = 118) or lifetime (n = 70) anxiety or unipolar mood disorder, not planning to quit in the next 6 months, were randomly assigned (1:1) to smoke either Usual Nicotine Content (UNC) (11.6 mg nicotine/cigarette) research cigarettes, or Reduced Nicotine Content (RNC) research cigarettes where the nicotine content per cigarette was progressively reduced to 0.2 mg in five steps over 18 weeks. Participants were then offered the choice to either receive assistance to quit smoking, receive free research cigarettes, or resume using their own cigarette brand during a 12-week follow-up period. Main outcomes were biomarkers of nicotine and toxicant exposure, smoking behavior and dependence and severity of psychiatric symptoms. The pre-registered primary outcome was plasma cotinine. RESULTS: A total of 143 (76.1%) randomized participants completed the randomized phase of the trial, 69 (73.4%) in the RNC group and 74 (78.8%) in the UNC group. After switching to the lowest nicotine content cigarettes, compared to smokers in the UNC group, at the last randomized visit the RNC group had significantly lower plasma cotinine (metabolite of nicotine): difference between groups, -175.7, 95% CI [-218.3, -133.1] ng/ml. Urine NNAL (metabolite of NNK, a lung carcinogen), exhaled carbon-monoxide, cigarette consumption, and cigarette dependence were also significantly lower in the RNC group than the UNC group. No between-group differences were found on a range of other biomarkers (e.g. 8-isoprostanes) or health indicators (e.g. blood pressure), or on 5 different psychiatric questionnaires, including the Kessler K6 measure of psychological distress. At the end of the subsequent 12-week treatment choice phase, those randomized to the RNC group were more likely to have quit smoking, based on initial intent-to-treat sample, n = 188 (18.1% RNC v 4.3% UNC, p = 0.004). CONCLUSION: Reducing nicotine content in cigarettes to very low levels reduces some toxicant exposures and cigarette addiction and increases smoking cessation in smokers with mood and/or anxiety disorders, without worsening mental health. TRIAL REGISTRATION: TRN: NCT01928758, registered August 21, 2013.

Quantification of Plasma 8-Isoprostane by High-Performance Liquid Chromatography with Tandem Mass Spectrometry in a Case-Control Study of Lung Cancer.

AIM: 8-iso-prostaglandin F2α is a biomarker of lipid peroxidation, and one of the most commonly used measures of oxidative stress. It is an established biomarker of lung cancer risk. It is commonly measured by enzyme-linked immunosorbent assay. Given its importance, we developed a stable isotope dilution UPLC-tandem mass spectrometric method for the rapid determination of 8-isoprostane in blood. METHODS: We tested the discriminatory capability of the method in 49 lung cancer patients, 55 benign lung nodule patients detected by chest X-ray, and 41 patients with chronic obstructive pulmonary disease (COPD) or asthma. RESULTS: Significant differences were found in mean 8-isoprostane levels between the three groups (p = 0.027), and post-hoc tests found higher levels in the lung cancer patients than in patients with benign nodules (p = 0.032) and COPD/asthma (p = 0.014). The receiving operating characteristic area under the curve (AUC) was 0.69 for differentiating the lung cancer group from the benign nodule group, and 0.7 for differentiating from the COPD/asthma group. CONCLUSIONS: The UPLC-MS/MS-based method is an efficient analytical tool for measuring 8-isoprostane plasma concentrations. The results suggest exploring its utility as a marker for early lung cancer screening.

Prevalence and determinants of meeting minimum dietary diversity among children aged 6-23 months in three sub-Saharan African Countries: The Demographic and Health Surveys, 2019-2020.

Background: Dietary diversity is an indicator of nutritional adequacy, which plays a significant role in child growth and development. Lack of adequate nutrition is associated with suboptimal brain development, lower school performance, and increased risk of mortality and chronic diseases. We aimed to determine the prevalence and determinants of meeting minimum dietary diversity (MDD), defined as consuming at least five out of eight basic food groups in the previous 24-h in three sub-Saharan African countries. Methods: A weighted population-based cross-sectional study was conducted using the most recent Demographic and Health Surveys (DHS). MDD data were available between 2019 and 2020 for three sub-Saharan African countries (Gambia, Liberia, and Rwanda). The study population included 5,832 children aged 6-23 months. A multivariable logistic regression model was developed to identify independent factors associated with meeting MDD. Results: Overall, the weighted prevalence of children who met the MDD was 23.2% (95% CI: 21.7-24.8%), ranging from 8.6% in Liberia to 34.4% in Rwanda. Independent factors associated with meeting MDD were: age of the child (OR) = 1.96, 95% CI: 1.61, 2.39 for 12-17 months vs. 6-11 months], mothers from highest households' wealth status (OR = 1.86, 95% CI: 1.45-2.39) compared with the lowest, and mothers with secondary/higher education (OR = 1.69, 95% CI: 1.35-2.12) compared with those with no education. Mothers who were employed, had access to a radio, and those who visited a healthcare facility in the last 12 months were more likely to meet the MDD. There was no significant association between the child's sex and the odds of fulfilling the MDD. Conclusions: There is substantial heterogeneity in the prevalence of MDD in these three sub-Saharan African countries. Lack of food availability or affordability may play a significant role in the low prevalence of MDD. The present analysis suggests that policies that will effectively increase the prevalence of meeting MDD should target poor households with appropriate materials or financial assistance and mothers with lower literacy. Public health interventions working with sectors such as education and radio stations to promote health education about the benefits of diverse diets is a critical step toward improving MDD in sub-Saharan Africa and preventing undernutrition.

Effect of menthol on nicotine reduction: Pooled results from two double-blind randomized controlled trials.

BACKGROUND: Menthol upregulates nicotinic acetylcholine receptors and is associated with tobacco dependence. The effects of menthol when smoking cigarettes with varying low nicotine content up to 98 % (e.g., non-addicting) less than commercial cigarettes is not well understood. The U.S. Food and Drug Administration is considering two tobacco product standards in cigarettes including banning menthol and reducing nicotine content. These new standards have the potential to significantly reduce smoking initiation and maintenance by limiting the mechanistic effects of nicotine and menthol on the brain. METHODS: We conducted two parallel randomized clinical trials of gradually reduced nicotine in cigarettes from 11.6 mg down to 0.2 mg nicotine/cigarette (very low nicotine content; VLNC) vs. usual nicotine content (11.6 mg; UNC) over an 18-week period in people who smoke cigarettes with low socioeconomic status (SES) and mental health conditions. RESULTS: Compared to UNC, VLNC was associated with significant reductions in cotinine, cigarettes per day, expired carbon monoxide levels, nicotine dependence and symptomology. These associations did not differ between menthol and non-menthol cigarettes, except people who smoke menthol cigarettes had less of a cotinine reduction in the SES trial. The pooled odds ratio of being adherent with using only VLNC study cigarettes in the gradual nicotine reduction arm for people who smoke non-menthol vs. menthol cigarettes was 2.6 (95 % CI:1.0, 6.4; p-value: 0.04). CONCLUSIONS: When nicotine is lowered to non-addicting levels, the results indicate an independent effect of menthol on the need to sustain nicotine intake in addicted people who smoke cigarettes.

Comparison of Carcinogen Biomarkers in Smokers of Menthol and Nonmenthol Cigarettes: The 2015-2016 National Health and Nutrition Examination Survey Special Sample.

BACKGROUND: The US FDA announced its commitment to prohibiting menthol as a characterizing flavor in tobacco. The relationship between cigarette menthol and exposure to toxic substances in mainstream tobacco smoke is not well characterized. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 2015 to 2016 special sample were used to study markers of 26 harmful and potentially harmful constituents (HPHC) in tobacco smoke. These include urine metabolites of polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), and heavy metals in exclusive menthol (n = 162) and nonmenthol (n = 189) cigarette smokers. Urine metabolites of 7 PAHs, 15 VOCs, and 4 heavy metal biomarkers were compared by menthol status. Multivariable analyses were conducted on creatinine-adjusted concentrations. RESULTS: There were no significant differences in cotinine levels or in 22 of 26 HPHCs. Among the urine metabolites of PAHs, the levels of 1-hydroxyphenanthrene were about 16% lower in menthol smokers. Among the urine metabolites of VOCs, menthol cigarette smokers presented significantly lower concentrations of acrylamide, N,N-dimethylformamide, and acrylonitrile. Menthol and nonmenthol smokers presented similar levels of heavy metals. Menthol did not affect the levels of cotinine and the nicotine metabolite ratio in urine. CONCLUSIONS: Menthol and nonmenthol cigarettes deliver similar levels of most HPHCs. IMPACT: Findings on toxicity are similar for menthol and nonmenthol cigarettes.

Feasibility of Patient Navigation-Based Smoking Cessation Program in Cancer Patients.

Continued smoking after a cancer diagnosis is causally associated with increased risks of all-cause and cancer-specific mortality, and of smoking-related second primary cancers. Patient navigation provides individualized assistance to address barriers to smoking cessation treatment and represents a promising bridge to smoking cessation in persons with cancer who smoke cigarettes. We conducted a single-arm interventional cohort study of current smokers identified through prospective health record screening and recruited from Penn State Cancer Institute outpatient clinics. Consented participants received two telephone intervention sessions and gain-framed messaging-based smoking cessation educational materials designed for persons with cancer. The primary study outcome was the feasibility of the patient navigation-based intervention; the secondary outcome was the engagement in smoking cessation treatment at the two-month follow-up. Of 1168 unique screened Cancer Institute patients, 134 (11.5%) were identified as current cigarette smokers. Among 67 patients approached at outpatient clinics, 24 (35.8%) were interested in participating, 12 (17.9%) were enrolled, eight (11.9%) completed the intervention sessions and study assessments, and six engaged in smoking cessation treatment. The participants expressed satisfaction with the intervention sessions (median = 8.5, scale 0-10). The low recruitment rates preclude patient navigation as a feasible method for connecting cancer patients to smoking cessation treatment resources.

Nighttime Waking to Smoke, Stress, and Nicotine Addiction.

INTRODUCTION: Up to one-half of cigarette smokers may wake up during the night and smoke. This behavior may result in greater likelihood of cessation failure, clinically relevant sleep difficulties, and a range of health issues. Whereas the scientific literature has often attributed this behavior to nicotine dependence, up to 85% of smokers who wake at night and smoke attribute this behavior to factors other than nicotine. This study examines the relations between nicotine dependence, psychological distress, perceived stress, and waking at night to smoke. METHODS: A total of 351 adult smokers from the Pennsylvania Adult Smoking Study (PASS) completed self-report surveys and provided saliva for the evaluation of cotinine values. Survey instruments included measures of nicotine addiction, perceived stress, a broad measure of global psychological distress, and a range of demographic factors. RESULTS: Logistic regression demonstrated that nicotine addiction, psychological distress, and perceived stress were all related to waking at night to smoke, but cotinine levels were not. Mediation models found that psychological distress had a direct relation to waking at night to smoke, even when considering nicotine addiction and other causes of sleep disturbances (e.g., apnea and chronic physical pain). Alternative moderation and mediation models were conducted but did not support other plausible associations between variables. CONCLUSIONS: Waking at night to smoke is likely the result of both nicotine dependence and psychological distress. Given that cotinine levels were not associated with waking at night, the mechanisms of how nicotine dependence may affect waking at night need further investigation.

Knowledge and Beliefs Regarding Harm From Specific Tobacco Products: Findings From the H.I.N.T. Survey.

PURPOSE: Determine whether dual tobacco users have different levels of knowledge about nicotine addiction, perceived harm beliefs of low nicotine cigarettes (LNCs) and beliefs about electronic cigarettes (e-cigarettes). DESIGN: Quantitative, Cross-sectional. SETTING: Health Information National Trends Survey 5 (Cycle 3, 2019). PARTICIPANTS: Nationally representative adult non-smokers (n=3113), exclusive cigarette smokers (n=302), and dual (cigarette and e-cigarette) users (n=77). MEASURES: The survey included single item measures on whether nicotine causes addiction and whether nicotine causes cancer. A five-point Likert scale assessed comparative harm of e-cigarettes and LNCs relative to conventional combustible cigarettes (1=much more harmful, 3=equally harmful…5 = much less harmful, or don't know). ANALYSIS: We used weighted multiple linear regression model to estimate means and 95% confidence intervals (CI) of e-cigarettes and LNCs beliefs by current tobacco user status. RESULTS: Over 97% of dual users, 83% of non-smokers and 86% of exclusive cigarette smokers correctly identified that nicotine is addictive. The majority of subjects incorrectly identified nicotine as a cause of cancer, with dual users having the lowest proportion of incorrect responses (60%). Dual users rated e-cigarette harmfulness as less harmful than combustibles (mean=2.20; 95% CI=1.73, 2.66) while exclusive cigarette smokers and non-smokers rated them as similarly harmful. LNCs were considered equally harmful and addictive as conventional cigarettes. CONCLUSION: Dual users had a higher knowledge base of tobacco-related health effects. The effectiveness of policies or medical recommendations to encourage smokers to switch from cigarettes to LNCs or e-cigarettes will need to consider accurate and inaccurate misperceptions about the harm and addictiveness of nicotine. Improved public health messages about different tobacco products are needed.

Mushroom intake and depression: A population-based study using data from the US National Health and Nutrition Examination Survey (NHANES), 2005-2016.

BACKGROUND: Mushrooms contain numerous bioactive compounds that may be associated with reduced anxiety including vitamin B12, nerve growth factor, antioxidants, and anti-inflammatory agents. We hypothesized that mushroom consumption is associated with a lower risk of depression in American adults. METHODS: Data from the National Health and Nutrition Examination Survey 2005-2016 was used. Up to two days of 24 h dietary recall were analyzed to assess mushroom intake frequency. Depression was measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). We used multivariable logistic regression models, adjusting for potential confounding factors. RESULTS: Among 24,699 participants (mean (SE) age: 45.5 (0.3) years), the weighted prevalence of depression was 5.9%. Mushrooms were consumed by 5.2% of participants. Compared with the lowest tertile of mushroom intake, participants in the middle tertile (median intake = 4.9 g/d, number of cases = 16) had lower odds of depression (adjusted OR = 0.31; 95% confidence interval [CI] 0.16, 0.60) while those in the highest tertile did not differ (median intake = 19.6 g/d, adjusted OR = 0.91; 95% CI: 0.47, 1.78, number of cases = 22) (P-trend = 0.42). LIMITATIONS: Cross-sectional data and lack of information on specific types of mushrooms consumed. CONCLUSION: Mushroom consumers had a lower odd of depression. However, we did not observe a dose-response relationship.

Changes in salivary proteome before and after cigarette smoking in smokers compared to sham smoking in nonsmokers: A pilot study.

INTRODUCTION: Smoking is the leading cause of preventable disease. Although smoking results in an acute effect of relaxation and positive mood through dopamine release, smoking is thought to increase stress symptoms such as heart rate and blood pressure from nicotine-induced effects on the HPA axis and increased cortisol. Despite the importance in understanding the mechanisms in smoking maintenance, little is known about the overall protein and physiological response to smoking. There may be multiple functions involved that if identified might help in improving methods for behavioral and pharmacological interventions. Therefore, our goal for this pilot study was to identify proteins in the saliva that change in response to an acute smoking event versus acute sham smoking event in smokers and non-smokers, respectively. METHODS: We employed the iTRAQ technique followed by Mass Spectrometry to identify differentially expressed proteins in saliva of smokers and non-smokers after smoking cigarettes and sham smoking, respectively. We also validated some of the salivary proteins by ELISA or western blotting. In addition, salivary cortisol and salivary amylase (sAA) activity were measured. RESULTS: In all, 484 salivary proteins were identified. Several proteins were elevated as well as decreased in smokers compared to non-smokers. Among these were proteins associated with stress response including fibrinogen alpha, cystatin A and sAA. Our investigation also highlights methodological considerations in study design, sampling and iTRAQ analysis. CONCLUSIONS: We suggest further investigation of other differentially expressed proteins in this study including ACBP, A2ML1, APOA4, BPIB1, BPIA2, CAH1, CAH6, CYTA, DSG1, EST1, GRP78, GSTO1, sAA, SAP, STAT, TCO1, and TGM3 that might assist in improving methods for behavioral and pharmacological interventions for smokers.

Household Smoking Restrictions, Time to First Cigarette and Tobacco Dependence.

OBJECTIVE: Environmental factors, such as household smoking restrictions (HSR), may impact a range of smoking-related outcomes. The current study examined the effects of various levels of HSR on smoking behaviors, including the number of cigarettes smoked per day and levels of nicotine dependence in a population of adult smokers. (1) Having specific HSR reduces the urges to smoke (path A); (2) having specific HSR reduces CPD (path B); (3) having specific HSR results in lower overall nicotine addiction (path C), and later, TTFC will be associated with (4) lower urges to smoke in the morning (path A'), (5) fewer CPD (path B'), and (6) lower levels of nicotine addiction (path C'). METHOD: Regression models using self-reported data from the Pennsylvania Adult Smoking Study (N = 353) were used. TTFC was measured minutes between waking and the first cigarette of the day. Household smoking restrictions were measured as follows: (1) full ban on smoking in the home, (2) partial ban, or (3) no ban. RESULTS: Subjects with no household smoking restrictions had lower incomes and education than those with at least some household smoking restrictions; those with full bans smoked less and had an earlier TTFC than those with at least some household smoking restrictions. Smokers with a full ban had a later TTFC, mediated by fewer cigarettes per day and lower cravings. Among those with partial bans, there is no reduction in cigarettes per day and an increase in urges to smoke. CONCLUSIONS: Partial household smoking restrictions are no better than no household smoking restrictions with regard to cigarettes per day and TTFC, and may cause an increase in urges to smoke in the morning.