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Item Open Access Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging.(Am J Psychiatry, 2002-06) Due, Deborah L; Huettel, Scott A; Hall, Warren G; Rubin, David COBJECTIVE: The authors sought to increase understanding of the brain mechanisms involved in cigarette addiction by identifying neural substrates modulated by visual smoking cues in nicotine-deprived smokers. METHOD: Event-related functional magnetic resonance imaging (fMRI) was used to detect brain activation after exposure to smoking-related images in a group of nicotine-deprived smokers and a nonsmoking comparison group. Subjects viewed a pseudo-random sequence of smoking images, neutral nonsmoking images, and rare targets (photographs of animals). Subjects pressed a button whenever a rare target appeared. RESULTS: In smokers, the fMRI signal was greater after exposure to smoking-related images than after exposure to neutral images in mesolimbic dopamine reward circuits known to be activated by addictive drugs (right posterior amygdala, posterior hippocampus, ventral tegmental area, and medial thalamus) as well as in areas related to visuospatial attention (bilateral prefrontal and parietal cortex and right fusiform gyrus). In nonsmokers, no significant differences in fMRI signal following exposure to smoking-related and neutral images were detected. In most regions studied, both subject groups showed greater activation following presentation of rare target images than after exposure to neutral images. CONCLUSIONS: In nicotine-deprived smokers, both reward and attention circuits were activated by exposure to smoking-related images. Smoking cues are processed like rare targets in that they activate attentional regions. These cues are also processed like addictive drugs in that they activate mesolimbic reward regions.Item Open Access AHRR Hypomethylation mediates the association between maternal smoking and metabolic profiles in children.(Hepatology communications, 2023-10) Vidal, Adriana C; Chandramouli, Shivram A; Marchesoni, Joddy; Brown, Nia; Liu, Yukun; Murphy, Susan K; Maguire, Rachel; Wang, Yaxu; Abdelmalek, Manal F; Mavis, Alisha M; Bashir, Mustafa R; Jima, Dereje; Skaar, David A; Hoyo, Cathrine; Moylan, Cynthia ABackground
Tobacco smoking during pregnancy is associated with metabolic dysfunction in children, but mechanistic insights remain limited. Hypomethylation of cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene is associated with in utero tobacco smoke exposure. In this study, we evaluated whether AHRR hypomethylation mediates the association between maternal smoking and metabolic dysfunction in children.Methods
We assessed metabolic dysfunction using liver fat content (LFC), serum, and clinical data in children aged 7-12 years (n=78) followed since birth. Maternal smoking was self-reported at 12 weeks gestation. Methylation was measured by means of pyrosequencing at 3 sequential CpG sites, including cg05575921, at birth and at ages 7-12. Regression models were used to evaluate whether AHRR methylation mediated the association between maternal smoking and child metabolic dysfunction.Results
Average AHRR methylation at birth was significantly higher among children of nonsmoking mothers compared with children of mothers who smoked (69.8% ± 4.4% vs. 63.5% ± 5.5, p=0.0006). AHRR hypomethylation at birth was associated with higher liver fat content (p=0.01), triglycerides (p=0.01), and alanine aminotransferase levels (p=0.03), and lower HDL cholesterol (p=0.01) in childhood. AHRR hypomethylation significantly mediated associations between maternal smoking and liver fat content (indirect effect=0.213, p=0.018), triglycerides (indirect effect=0.297, p=0.044), and HDL cholesterol (indirect effect = -0.413, p=0.007). AHRR methylation in childhood (n=78) was no longer significantly associated with prenatal smoke exposure or child metabolic parameters (p>0.05).Conclusions
AHRR hypomethylation significantly mediates the association between prenatal tobacco smoke exposure and features of childhood metabolic dysfunction, despite the lack of persistent hypomethylation of AHRR into childhood. Further studies are needed to replicate these findings and to explore their causal and long-term significance.Item Restricted Are mature smokers misinformed?(J Health Econ, 2009-03) Khwaja, Ahmed; Silverman, Dan; Sloan, Frank; Wang, YangWhile there are many reasons to continue to smoke in spite of its consequences for health, the concern that many smoke because they misperceive the risks of smoking remains a focus of public discussion and motivates tobacco control policies and litigation. In this paper we investigate the relative accuracy of mature smokers' risk perceptions about future survival, and a range of morbidities and disabilities. Using data from the survey on smoking (SOS) conducted for this research, we compare subjective beliefs elicited from the SOS with corresponding individual-specific objective probabilities estimated from the health and retirement study. Overall, consumers in the age group studied, 50-70, are not overly optimistic in their perceptions of health risk. If anything, smokers tend to be relatively pessimistic about these risks. The finding that smokers are either well informed or pessimistic regarding a broad range of health risks suggests that these beliefs are not pivotal in the decision to continue smoking. Although statements by the tobacco companies may have been misleading and thus encouraged some to start smoking, we find no evidence that systematic misinformation about the health consequences of smoking inhibits quitting.Item Open Access Are quit attempts among U.S. female nurses who smoke different from female smokers in the general population? An analysis of the 2006/2007 tobacco use supplement to the current population survey.(BMC Womens Health, 2012-03-19) Sarna, Linda; Bialous, Stella Aguinaga; Nandy, Karabi; Yang, QingBACKGROUND: Smoking is a significant women's health issue. Examining smoking behaviors among occupational groups with a high prevalence of women may reveal the culture of smoking behavior and quit efforts of female smokers. The purpose of this study was to examine how smoking and quitting characteristics (i.e., ever and recent quit attempts) among females in the occupation of nursing are similar or different to those of women in the general population. METHODS: Cross-sectional data from the Tobacco Use Supplement of the Current Population Survey 2006/2007 were used to compare smoking behaviors of nurses (n = 2, 566) to those of non-healthcare professional women (n = 93, 717). Smoking characteristics included years of smoking, number of cigarettes, and time to first cigarette with smoking within the first 30 minutes as an indicator of nicotine dependence. Logistic regression models using replicate weights were used to determine correlates of ever and previous 12 months quit attempts. RESULTS: Nurses had a lower smoking prevalence than other women (12.1% vs 16.6%, p < 0.0001); were more likely to have ever made a quit attempt (77% vs 68%, p = 0.0002); but not in the previous 12 months (42% vs 43%, p = 0.77). Among those who ever made a quit attempt, nurses who smoked within 30 minutes of waking, were more likely to have made a quit attempt compared to other women (OR = 3.1, 95% CI: 1.9, 5.1). When considering quit attempts within the last 12 months, nurses whose first cigarette was after 30 minutes of waking were less likely to have made a quit attempt compared to other females (OR = 0.69, 95% CI: 0.49, 0.98). There were no other significant differences in ever/recent quitting. CONCLUSIONS: Smoking prevalence among female nurses was lower than among women who were not in healthcare occupations, as expected. The lack of difference in recent quit efforts among female nurses as compared to other female smokers has not been previously reported. The link between lower level of nicotine dependence, as reflected by the longer time to first cigarette, and lower quit attempts among nurses needs further exploration.Item Open Access Are State legislatures responding to public opinion when allocating funds for tobacco control programs?(Health Promot Pract, 2004-07) Snyder, Angela; Falba, Tracy; Busch, Susan; Sindelar, JodyThis study explored the factors associated with state-level allocations to tobacco-control programs. The primary research question was whether public sentiment regarding tobacco control was a significant factor in the states' 2001 budget decisions. In addition to public opinion, several additional political and economic measures were considered. Significant associations were found between our outcome, state-level tobacco-control funding per capita, and key variables of interest including public opinion, amount of tobacco settlement received, the party affiliation of the governor, the state's smoking rate, excise tax revenue received, and whether the state was a major producer of tobacco. The findings from this study supported our hypothesis that states with citizens who favor more restrictive indoor air policies allocate more to tobacco control. Effective public education to change public opinion and the cultural norms surrounding smoking may affect political decisions and, in turn, increase funding for crucial public health programs.Item Open Access Assessing the Evidence on the Differential Impact of Menthol versus Non-menthol Cigarette Use on Initiation and Progression to Regular Smoking: A Systematic Review and Meta-analysis.(American journal of health behavior, 2022-04) Kim, Mimi M; Curtin, Geoffrey MBackground: Despite numerous assessments of the public health impact of menthol cigarettes, a rigorous synthesis related to menthol cigarettes and behavioral outcomes is lacking. This systematic review and meta-analysis examined the question: Does menthol cigarette use have a differential impact on initiation and progression to regular smoking compared to non-menthol cigarette use? Methods: We consulted 6 databases from their inception to October 15, 2021. We included articles comparing menthol versus non-menthol smokers among 4 predefined smoking initiation and progression outcomes. We assessed risk of bias was using the Agency for Healthcare Research and Quality Evidence-Based Practice Center approach. We applied a random-effects model to pool adjusted odds ratios. Results: We qualitatively synthesized 16 adjusted studies across the outcomes. Results from one meta-analysis suggested no difference between menthol and non-menthol smokers in likelihood to report daily versus non-daily smoking. Conclusion: This systematic review and meta-analysis did not identify a consistent, statistically significant, or differential association between menthol use and progression to regular smoking. Varying definitions of outcome measures and lack of longitudinal evidence limited the confident conclusions that could be drawn from this evidence base.Item Open Access Assessing the evidence on the differential impact of menthol versus non-menthol cigarette use on smoking cessation in the U.S. population: a systematic review and meta-analysis.(Substance abuse treatment, prevention, and policy, 2021-08) Kim, Mimi M; Kim, Mimi M; Curtin, Geoffrey MBackground
The potential impact of menthol versus non-menthol cigarette use on smoking behaviors is an intensely scrutinized topic in the public health arena. To date, several general literature reviews have been conducted, but findings and conclusions have been discordant. This systematic review followed PRISMA guidelines to examine the Key Question, "Does menthol cigarette use have a differential impact on smoking cessation compared with non-menthol cigarette use?"Methods
Six databases-Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, MEDLINE, Embase and PsycInfo-were queried from inception to June 12, 2020. Articles comparing menthol versus non-menthol cigarette smokers in terms of at least one predefined smoking cessation outcome were included. Risk of bias was assessed using the Agency for Healthcare Research and Quality Evidence-Based Practice Center approach. A random-effects model utilizing the DerSimonian and Laird method to pool adjusted odds ratio was applied. Variations among pooled studies were assessed using Cochran's Q statistic, and heterogeneity was quantified using the inconsistency index (I2).Results
Forty-three demographically adjusted studies (22 rated "good", 20 rated "fair", and one study rated "poor" individual study quality) comparing menthol and non-menthol smokers were qualitatively synthesized across the following measures (study count; strength of evidence): duration of abstinence (2; low); quit attempts (15; insufficient); rate of abstinence/quitting (29; moderate); change in smoking quantity/frequency (5; insufficient); and, return to smoking/relapse (2; insufficient). Overall, the qualitative synthesis failed to show a consistent trend for an association between menthol cigarette use and smoking cessation across outcomes. Meta-analyses found no difference between menthol and non-menthol cigarette use and either quit attempts or abstinence.Conclusions
Given the lack of consistency or statistical significance in the findings-combined with a "low" overall strength of evidence grade, based on deficiencies of indirectness and inconsistency-no consistent or significant associations between menthol cigarette use and smoking cessation were identified. Recommendations for future studies include increased focus on providing longitudinal, adjusted data collected from standardized outcome measures of cessation to better inform long-term smoking cessation and menthol cigarette use. Such improvements should also be further considered in more methodologically rigorous systematic reviews characterized by objectivity, comprehensiveness, and transparency with the ultimate objective of better informing public health and policy decision making.Item Open Access Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck.(BMC cancer, 2011-06-20) Ma, Hongxia; Wang, Li-E; Liu, Zhensheng; Sturgis, Erich M; Wei, QingyiPhospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN.We genotyped three potentially functional SNPs (rs2274223A/G, rs3203713A/G and rs11599672T/G) of PLCE1 in 1,098 SCCHN patients and 1,090 controls matched by age and sex in a non-Hispanic white population.Although none of three SNPs was alone significantly associated with overall risk of SCCHN, their combined effects of risk alleles (rs2274223G, rs3203713G and rs11599672G) were found to be associated with risk of SCCHN in a locus-dose effect manner (Ptrend=0.046), particularly for non-oropharyngeal tumors (Ptrend=0.017); specifically, rs2274223 was associated with a significantly increased risk (AG vs. AA: adjusted OR=1.29, 95% CI=1.01-1.64; AG/GG vs. AA: adjusted OR=1.30, 95% CI=1.03-1.64), while rs11599672 was associated with a significantly decreased risk (GG vs. TT: adjusted OR=0.54, 95% CI=0.34-0.86; TG/GG vs. TT: adjusted OR=0.76, 95% CI=0.61-0.95).Our findings suggest that PLCE1 variants may have an effect on risk of SCCHN associated with tobacco and alcohol exposure, particularly for those tumors arising at non-oropharyngeal sites. These findings, although need to be validated by larger studies, are consistent with those in esophageal and gastric cancers.Item Open Access Associations between cigarette smoking and pain among veterans.(Epidemiologic reviews, 2015-01-16) Chapman, Shawna L Carroll; Wu, Li-TzyIndividuals with chronic pain often report using cigarettes to cope, and smoking and chronic pain appear prevalent among US veterans. Pain may be a barrier to cigarette cessation and abstinence in this population. Because of physiological effects, smoking cigarettes may also interfere with pain management. A better understanding of how cigarette use relates to pain may assist in veteran cigarette cessation and pain management efforts. To assist these efforts, we searched the literature using keywords, such as "pain," "smoking," and "veteran," to identify 23 journal articles published from 1993 to 2013 that reported on studies examining pain and smoking variables among military or veteran populations. Studies found that veterans reported using cigarettes to cope with pain, there was greater occurrence of pain and disability among smokers in the military, and smoking increased the odds of veterans receiving an opioid prescription for pain and misusing opioids. Studies also found increased odds of pain and smoking among Veterans Health Administration patients with post-traumatic stress disorder when compared with those without post-traumatic stress disorder. Studies support an interaction between pain and smoking among veterans. However, the mechanisms underlying this relationship remain unclear. Future studies focused on this interaction would benefit veteran populations.Item Open Access Burning a hole in the budget: tobacco spending and its crowd-out of other goods.(Appl Health Econ Health Policy, 2004) Busch, Susan H; Jofre-Bonet, Mireia; Falba, Tracy A; Sindelar, Jody LSmoking is an expensive habit. Smoking households spend, on average, more than $US1000 annually on cigarettes. When a family member quits, in addition to the former smoker's improved long-term health, families benefit because savings from reduced cigarette expenditures can be allocated to other goods. For households in which some members continue to smoke, smoking expenditures crowd-out other purchases, which may affect other household members, as well as the smoker. We empirically analyse how expenditures on tobacco crowd-out consumption of other goods, estimating the patterns of substitution and complementarity between tobacco products and other categories of household expenditure. We use the Consumer Expenditure Survey data for the years 1995-2001, which we complement with regional price data and state cigarette prices. We estimate a consumer demand system that includes several main expenditure categories (cigarettes, food, alcohol, housing, apparel, transportation, medical care) and controls for socioeconomic variables and other sources of observable heterogeneity. Descriptive data indicate that, comparing smokers to nonsmokers, smokers spend less on housing. Results from the demand system indicate that as the price of cigarettes rises, households increase the quantity of food purchased, and, in some samples, reduce the quantity of apparel and housing purchased.Item Open Access COPD: balancing oxidants and antioxidants.(Int J Chron Obstruct Pulmon Dis, 2015) Fischer, Bernard M; Voynow, Judith A; Ghio, Andrew JChronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in the world. The disease encompasses emphysema, chronic bronchitis, and small airway obstruction and can be caused by environmental exposures, primarily cigarette smoking. Since only a small subset of smokers develop COPD, it is believed that host factors interact with the environment to increase the propensity to develop disease. The major pathogenic factors causing disease include infection and inflammation, protease and antiprotease imbalance, and oxidative stress overwhelming antioxidant defenses. In this review, we will discuss the major environmental and host sources for oxidative stress; discuss how oxidative stress regulates chronic bronchitis; review the latest information on genetic predisposition to COPD, specifically focusing on oxidant/antioxidant imbalance; and review future antioxidant therapeutic options for COPD. The complexity of COPD will necessitate a multi-target therapeutic approach. It is likely that antioxidant supplementation and dietary antioxidants will have a place in these future combination therapies.Item Open Access Determinants of Tobacco Initiation among Young People of Palau(2018) Pu, WilliamBackground: Tobacco control and cessation among the youth in Palau is becoming a chief concern in non-communicable disease control within the Palauan Ministry of Health. The most current research states that the trend of tobacco use and initiation among the youth in Palau is ever-increasing. This study seeks to quantitively and qualitatively explore the exposures to tobacco use in daily life in order to inform future health interventions and programs.
Methods: This study was a mixed methods cross-section study seeking to explore many aspects of tobacco exposure and use among the young people of Palau. Survey questions assessing knowledge, behavior, and attitudes regarding tobacco use were conducted with Palauan youth ages 9 to 18 years across various states of Palau. Three focus groups were also conducted to provide depth to collected qualitative data regarding domains such as tobacco initiation, acquisition, and social exposure. Qualitative analysis was conducted using Stata 14 and qualitative data was examined using Nvivo 11.
Results: 39 individuals participated in the survey portion of the study. Of the 39 participants 18 were tobacco users with the majority of users initiating tobacco use before the age of 12. The most common reason stated for tobacco initiation behavior was peer pressure and curiosity. With regard to smoking cigarettes, 82% of respondents believed it causes great harm. Whereas only 43.6% of respondents believed that chewing betel with tobacco caused great harm. Over half of ever users of tobacco (57.1%) had at least one friend who uses tobacco. Methods of tobacco acquisition, perception of tobacco use harm, tobacco imitation reasons, and tobacco exposures in daily life were themes collected from focus group discussions.
Conclusions: This study offers insight into certain characteristics of tobacco users, tobacco initiating behavior in young Palauans, attitudes and beliefs towards tobacco, as well as methods of tobacco acquisition. The results of this study emphasize a need for stricter regulation and enforcement of the tobacco policies which are in place. Though knowledge regarding the harms of tobacco are relatively high, there are still misconceptions that exist in understanding the harms of tobacco. One of the intentions of this study is to provide insight to further inform future health interventions targeting young Palauans which use tobacco. Further research should be implemented within this topic in order to fully understand the nuances and intricacies which surround the role of tobacco in the lives of young Palauans.
Item Open Access Does smoking have an impact on fusion rate in single-level anterior cervical discectomy and fusion with allograft and rigid plate fixation? Clinical article.(Journal of neurosurgery. Spine, 2013-11) Luszczyk, Myles; Smith, Justin S; Fischgrund, Jeffrey S; Ludwig, Steven C; Sasso, Rick C; Shaffrey, Christopher I; Vaccaro, Alexander RObject
Although smoking has been shown to negatively affect fusion rates in patients undergoing multilevel fusions of the cervical and lumbar spine, the effect of smoking on fusion rates in patients undergoing single-level anterior cervical discectomy and fusion (ACDF) with allograft and plate fixation has yet to be thoroughly investigated. The objective of the present study was to address the effect of smoking on fusion rates in patients undergoing a 1-level ACDF with allograft and a locked anterior cervical plate.Methods
This study is composed of patients from the control groups of 5 separate studies evaluating the use of an anterior cervical disc replacement to treat cervical radiculopathy. For each of the 5 studies the control group consisted of patients who underwent a 1-level ACDF with allograft and a locked cervical plate. The authors of the present study reviewed data obtained in a total of 573 patients; 156 patients were smokers and 417 were nonsmokers. A minimum follow-up period of 24 months was required for inclusion in this study. Fusion status was assessed by independent observers using lateral, neutral, and flexion/extension radiographs.Results
An overall fusion rate of 91.4% was achieved in all 573 patients. A solid fusion was shown in 382 patients (91.6%) who were nonsmokers. Among patients who were smokers, 142 (91.0%) had radiographic evidence of a solid fusion. A 2-tailed Fisher exact test revealed a p value of 0.867, indicating no difference in the union rates between smokers and nonsmokers.Conclusions
The authors found no statistically significant difference in fusion status between smokers and nonsmokers who underwent a single-level ACDF with allograft and a locked anterior cervical plate. Although the authors do not promote tobacco use, it appears that the use of allograft with a locked cervical plate in single-level ACDF among smokers produces similar fusion rates as it does in their nonsmoking counterparts.Item Open Access E-cigarette prevalence and correlates of use among adolescents versus adults: a review and comparison.(Journal of psychiatric research, 2014-07) Carroll Chapman, Shawna L; Wu, Li-TzyPerceived safer than tobacco cigarettes, prevalence of electronic cigarette (e-cigarette) use is increasing. Analyses of cartridges suggest that e-cigarettes may pose health risks. In light of increased use and the potential for consequences, we searched Google Scholar and Pubmed in July of 2013 using keywords, such as e-cigarette and vaping, to compare differences and similarities in prevalence and correlates of e-cigarette use among adolescents (grades 6-12) versus adults (aged ≥18 years). Twenty-one studies focused on e-cigarette use. Ever-use increased among various age groups. In 2011, ever-use was highest among young adults (college students and those aged 20-28; 4.9%-7.0%), followed by adults (aged ≥18; 0.6%-6.2%), and adolescents (grades 6-12 and aged 11-19; <1%-3.3%). However, in 2012 adolescent ever-use increased to 6.8% and, among high school students, went as high as 10.0%. While the identified common correlate of e-cigarette use was a history of cigarette smoking, a notable proportion of adolescents and young adults who never smoked cigarettes had ever-used e-cigarettes. E-cigarette use was not consistently associated with attempting to quit tobacco among young adults. Adults most often reported e-cigarettes as a substitute for tobacco, although not always to quit. Reviewed studies showed a somewhat different pattern of e-cigarette use among young people (new e-cigarette users who had never used tobacco) versus adults (former or current tobacco users). Research is needed to better characterize prevalences, use correlates, and motives of use in different population groups, including how adolescent and young adult experimentation with e-cigarettes relates to other types of substance use behaviors.Item Open Access Effects of varenicline and cognitive bias modification on neural response to smoking-related cues: study protocol for a randomized controlled study.(Trials, 2014-10-07) Attwood, Angela S; Williams, Tim; Adams, Sally; McClernon, Francis J; Munafò, Marcus RBACKGROUND: Smoking-related cues can trigger drug-seeking behaviors, and computer-based interventions that reduce cognitive biases towards such cues may be efficacious and cost-effective cessation aids. In order to optimize such interventions, there needs to be better understanding of the mechanisms underlying the effects of cognitive bias modification (CBM). Here we present a protocol for an investigation of the neural effects of CBM and varenicline in non-quitting daily smokers. METHODS/DESIGN: We will recruit 72 daily smokers who report smoking at least 10 manufactured cigarettes or 15 roll-ups per day and who smoke within one hour of waking. Participants will attend two sessions approximately one week apart. At the first session participants will be screened for eligibility and randomized to receive either varenicline or a placebo over a seven-day period. On the final drug-taking day (day seven) participants will attend a second session and be further randomized to one of three CBM conditions (training towards smoking cues, training away from smoking cues, or control training). Participants will then undergo a functional magnetic resonance imaging scan during which they will view smoking-related pictorial cues. Primary outcome measures are changes in cognitive bias as measured by the visual dot-probe task, and neural responses to smoking-related cues. Secondary outcome measures will be cognitive bias as measured by a transfer task (modified Stroop test of smoking-related cognitive bias) and subjective mood and cigarette craving. DISCUSSION: This study will add to the relatively small literature examining the effects of CBM in addictions. It will address novel questions regarding the neural effects of CBM. It will also investigate whether varenicline treatment alters neural response to smoking-related cues. These findings will inform future research that can develop behavioral treatments that target relapse prevention. TRIAL REGISTRATION: Registered with Current Controlled Trials: ISRCTN65690030. Registered on 30 January 2014.Item Open Access Emphysema-associated Autoreactive Antibodies Exacerbate Post-Lung Transplant Ischemia-Reperfusion Injury.(American journal of respiratory cell and molecular biology, 2019-06) Patel, Kunal J; Cheng, Qi; Stephenson, Sarah; Allen, D Patterson; Li, Changhai; Kilkenny, Jane; Finnegan, Ryan; Montalvo-Calero, Valeria; Esckilsen, Scott; Vasu, Chentha; Goddard, Martin; Nadig, Satish N; Atkinson, CarlChronic obstructive pulmonary disease-associated chronic inflammation has been shown to lead to an autoimmune phenotype characterized in part by the presence of lung autoreactive antibodies. We hypothesized that ischemia-reperfusion injury (IRI) liberates epitopes that would facilitate preexisting autoantibody binding, thereby exacerbating lung injury after transplant. We induced emphysema in C57BL/6 mice through 6 months of cigarette smoke (CS) exposure. Mice with CS exposure had significantly elevated serum autoantibodies compared with non-smoke-exposed age-matched (NS) mice. To determine the impact of a full preexisting autoantibody repertoire on IRI, we transplanted BALB/c donor lungs into NS or CS recipients and analyzed grafts 48 hours after transplant. CS recipients had significantly increased lung injury and immune cell infiltration after transplant. Immunofluorescence staining revealed increased IgM, IgG, and C3d deposition in CS recipients. To exclude confounding alloreactivity and confirm the role of preexisting autoantibodies in IRI, syngeneic Rag1-/- (recombination-activating protein 1-knockout) transplants were performed in which recipients were reconstituted with pooled serum from CS or NS mice. Serum from CS-exposed mice significantly increased IRI compared with control mice, with trends in antibody and C3d deposition similar to those seen in allografts. These data demonstrate that pretransplant CS exposure is associated with increased IgM/IgG autoantibodies, which, upon transplant, bind to the donor lung, activate complement, and exacerbate post-transplant IRI.Item Open Access Essays on Health Economics(2009) Wang, YangIn this dissertation, I discuss two important factors in individuals' decision-making processes: subjective expectation bias and time-inconsistent preferences. In Chapter I, I look at how individuals' own subjective expectations about certain future events are different from what actually happens in the future, even after controlling for individuals' private information. This difference, which is defined as the expectation bias in this paper, is found to have important influence on individuals' choices. Specifically, I look into the relationship between US elderly's subjective longevity expectation biases and their smoking choices. I find that US elderly tend to over-emphasize the importance of their genetic makeup but underestimate the influence of their health-related choices, such as smoking, on their longevity. This finding can partially explain why even though US elderly are found to be more concerned with their health and more forward-looking than we would have concluded using a model which does not allow for subjective expectation bias, we still observe many smokers. The policy simulation further confirms that if certain public policies can be designed to correct individuals' expectation biases about the effects of their genes and health-related choices on their longevity, then the average smoking rate for the age group analyzed in this paper will go down by about 4%.
In Chapter II, my co-author, Hanming Fang, and I look at one possible explanation to the under-utilization of preventive health care in the United States: procrastination. Procrastination, the phenomenon that individuals postpone certain decisions which incur instantaneous costs but bring long-term benefits, is captured in economics by hyperbolic discount factors and the corresponding time-inconsistent preferences. This chapter extends the semi-parametric identification and estimation method for dynamic discrete choice models using Hotz and Miller's (1993) conditional choice probability approach to the setting where individuals may have hyperbolic discounting time preferences and may be naive about their time inconsistency. We implement the proposed estimation method to US adult women's decisions of undertaking mammography tests to evaluate the importance of present bias and naivety in the under-utilization of mammography, controlling for other potentially important explanatory factors such as age, race, household income, and marital status. Preliminary results show evidence for both present bias and naivety in adult women's decisions of undertaking mammography tests. Using the parameters estimated, we further conduct some policy simulations to quantify the effects of the present bias and naivety on the utilization of preventive health care in the US.
Item Open Access Evaluation of the association between maternal smoking, childhood obesity, and metabolic disorders: a national toxicology program workshop review.(Environmental health perspectives, 2013-02) Behl, Mamta; Rao, Deepa; Aagaard, Kjersti; Davidson, Terry L; Levin, Edward D; Slotkin, Theodore A; Srinivasan, Supriya; Wallinga, David; White, Morris F; Walker, Vickie R; Thayer, Kristina A; Holloway, Alison CBackground
An emerging literature suggests that environmental chemicals may play a role in the development of childhood obesity and metabolic disorders, especially when exposure occurs early in life.Objective
Here we assess the association between these health outcomes and exposure to maternal smoking during pregnancy as part of a broader effort to develop a research agenda to better understand the role of environmental chemicals as potential risk factors for obesity and metabolic disorders.Methods
PubMed was searched up to 8 March 2012 for epidemiological and experimental animal studies related to maternal smoking or nicotine exposure during pregnancy and childhood obesity or metabolic disorders at any age. A total of 101 studies-83 in humans and 18 in animals-were identified as the primary literature.Discussion
Current epidemiological data support a positive association between maternal smoking and increased risk of obesity or overweight in offspring. The data strongly suggest a causal relation, although the possibility that the association is attributable to unmeasured residual confounding cannot be completely ruled out. This conclusion is supported by findings from laboratory animals exposed to nicotine during development. The existing literature on human exposures does not support an association between maternal smoking during pregnancy and type 1 diabetes in offspring. Too few human studies have assessed outcomes related to type 2 diabetes or metabolic syndrome to reach conclusions based on patterns of findings. There may be a number of mechanistic pathways important for the development of aberrant metabolic outcomes following perinatal exposure to cigarette smoke, which remain largely unexplored.Conclusions
From a toxicological perspective, the linkages between maternal smoking during pregnancy and childhood overweight/obesity provide proof-of-concept of how early-life exposure to an environmental toxicant can be a risk factor for childhood obesity.Item Open Access Five-Factor Model personality profiles of drug users.(BMC psychiatry, 2008-04-11) Terracciano, Antonio; Löckenhoff, Corinna E; Crum, Rosa M; Bienvenu, O Joseph; Costa, Paul TBackground
Personality traits are considered risk factors for drug use, and, in turn, the psychoactive substances impact individuals' traits. Furthermore, there is increasing interest in developing treatment approaches that match an individual's personality profile. To advance our knowledge of the role of individual differences in drug use, the present study compares the personality profile of tobacco, marijuana, cocaine, and heroin users and non-users using the wide spectrum Five-Factor Model (FFM) of personality in a diverse community sample.Method
Participants (N = 1,102; mean age = 57) were part of the Epidemiologic Catchment Area (ECA) program in Baltimore, MD, USA. The sample was drawn from a community with a wide range of socio-economic conditions. Personality traits were assessed with the Revised NEO Personality Inventory (NEO-PI-R), and psychoactive substance use was assessed with systematic interview.Results
Compared to never smokers, current cigarette smokers score lower on Conscientiousness and higher on Neuroticism. Similar, but more extreme, is the profile of cocaine/heroin users, which score very high on Neuroticism, especially Vulnerability, and very low on Conscientiousness, particularly Competence, Achievement-Striving, and Deliberation. By contrast, marijuana users score high on Openness to Experience, average on Neuroticism, but low on Agreeableness and Conscientiousness.Conclusion
In addition to confirming high levels of negative affect and impulsive traits, this study highlights the links between drug use and low Conscientiousness. These links provide insight into the etiology of drug use and have implications for public health interventions.Item Open Access Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST).(BMC public health, 2011-01-21) Hoyo, Cathrine; Murtha, Amy P; Schildkraut, Joellen M; Forman, Michele R; Calingaert, Brian; Demark-Wahnefried, Wendy; Kurtzberg, Joanne; Jirtle, Randy L; Murphy, Susan KBackground
Folic acid (FA) added to foods during fortification is 70-85% bioavailable compared to 50% of folate occurring naturally in foods. Thus, if FA supplements also are taken during pregnancy, both mother and fetus can be exposed to FA exceeding the Institute of Medicine's recommended tolerable upper limit (TUL) of 1,000 micrograms per day (μg/d) for adult pregnant women. The primary objective is to estimate the proportion of women taking folic acid (FA) doses exceeding the TUL before and during pregnancy, and to identify correlates of high FA use.Methods
During 2005-2008, pre-pregnancy and pregnancy-related data on dietary supplementation were obtained by interviewing 539 pregnant women enrolled at two obstetrics-care facilities in Durham County, North Carolina.Results
Before pregnancy, 51% of women reported FA supplementation and 66% reported this supplementation during pregnancy. Before pregnancy, 11.9% (95% CI = 9.2%-14.6%) of women reported supplementation with FA doses above the TUL of 1,000 μg/day, and a similar proportion reported this intake prenatally. Before pregnancy, Caucasian women were more likely to take FA doses above the TUL (OR = 2.99; 95% = 1.28-7.00), compared to African American women, while women with chronic conditions were less likely to take FA doses above the TUL (OR = 0.48; 95%CI = 0.21-0.97). Compared to African American women, Caucasian women were also more likely to report FA intake in doses exceeding the TUL during pregnancy (OR = 5.09; 95%CI = 2.07-12.49).Conclusions
Fifty-one percent of women reported some FA intake before and 66% during pregnancy, respectively, and more than one in ten women took FA supplements in doses that exceeded the TUL. Caucasian women were more likely to report high FA intake. A study is ongoing to identify possible genetic and non-genotoxic effects of these high doses.