This study examined which particular facets of mindfulness (nonreactivity, observing thoughts and feelings, acting with awareness, describing experience, and nonjudging of experience) accounted for improvements in mood and warning signs of relapse in an adult population. This exploratory study examined the impact of the five facets of mindfulness on both warning signs of relapse and mood in a primarily minority adult population in a residential substance abuse treatment facility. Results showed that all five facets were significantly correlated with mood and warning signs at the bivariate level. When considering the facets together, observing and nonjudging were related to mood, and acting with awareness and nonjudging were related to warning signs. Implications for future research and practice are offered.

Researchers have shown a relationship between mental health disorders and alcohol dependence. However, only 5-10% of individuals with substance use problems co-occurring with mental health problems are correctly identified. The purpose of this research was to identify predictors of relapse using three different instruments of varying complexity: the Patient Health Questionnaire-9 (PHQ-9), the Modified Mini Screen (MMS), and the Millon Clinical Multiaxial Inventory-III (MCMI-III). Researchers have found that using alcohol produces relief, similar to a pharmacological intervention, from troublesome mental health symptoms that individuals experience. Considering this association, the self-medication hypothesis was the conceptual lens used for the study as it provides a practical framework for analyzing the relationship between mental health disorders and relapse. At the request of this researcher, data were collected on 45 individuals who were provided detoxification services at a public treatment facility in central Wisconsin. Regression analyses were conducted and identified a statistically significant, although weak, predictive relationship between relapse and the variable of depression as measured by the PHQ-9 (R = .311a, R2 = .097, p = .037), and depression as measured by the MCMI-III (R = .364a, R2 = .133, p = .014). The implications for positive social change from this study include the potential to increase the effectiveness and efficiency in identifying co-occurring mental health disorders among individuals who are treated for alcohol detoxification, enhancing the accuracy of referrals for aftercare, and reducing readmissions for detoxification amongst the individuals served.

Indiana University-Purdue University Indianapolis (IUPUI) / The smoking rate of low-income pregnant women is almost 4 times the rate for higher-income women. A better understanding of smoking within the low-income population is needed. The purpose of this dissertation was to study smoking and related factors for pregnant and postpartum women living in poverty. The first component used Rodger’s evolutionary concept analysis method and uncovered three attributes, four antecedents, and three consequences for smoking cessation. The second (N = 1,554) and third (N = 71,944) components were a secondary data analysis of first-pregnancy Medicaid-eligible women enrolled in the Nurse-Family Partnership program from 2011-2016. The second component explored patterns of smoking and depression and their associations. Eight distinct patterns of smoking and depression were found. Smokers were more likely than nonsmokers to have depressive symptoms at the end of pregnancy (OR = 1.37 [1.04, 1.81] and 12 months post-delivery (OR = 1.93 [1.47, 2.51]. The third component investigated covariates present during early pregnancy and their relationships with smoking status and sought to find best fitting predictive models. Multivariable logistic regression showed cigarette use in the 3 months prior to pregnancy and at program intake were significant predictors for smoking status at the end of pregnancy and 12 months post-delivery. Interactive Matrix Language, Structured Query Language, and iterations of logistic regression identified 5 covariates (high school education, cigarette use prior to pregnancy, smoking status at pregnancy baseline, depression, and self-mastery) for the best fitting model at the end of pregnancy and three additional covariates (post-secondary education, marital status, and race) for the 12 months post-delivery model. The area under the receiver operator characteristic curve was 0.9681 for the end of pregnancy model and 0.9269 for 12 months post-delivery model, indicating excellent prediction ability of the models. Results can be integrated in smoking prevention education, screening, and cessation intervention programs.

No description available.

Opioid use disorder is a chronic, relapsing disease, with more than 85% of individuals experiencing a relapse episode within one year. One common reason patients relapse is due to intense cravings, which are defined as the compulsive urge to use the drug. In fact, craving was recently added to the DSM criteria for substance use disorder diagnosis. Counterintuitively, cravings intensify over the course of extended abstinence, especially in response to drug-paired cues, a phenomenon known as “incubation of craving”. This contributes to difficulty in maintaining long-term sobriety. The mesocorticolimbic reward pathway facilitates self-administration and cue-induced incubation of craving for drugs of abuse and natural rewards, such as sucrose. In particular, the shell sub-region of the nucleus accumbens is a critical brain region involved in context/cue-mediated reward seeking. In the experiments described here, we utilized an incubation of craving model, in which male and female rats self-administered opioids (morphine or heroin) or sucrose for 10 days. Sucrose served as an important control for delineating drug-induced changes from those caused in response to natural rewards, which are not the intended target of potential treatments. Reward delivery was paired with a cue light that was later used to elicit craving. After self-administration, rats underwent brief (one day) or extended (30 days) forced abstinence. One or 30 days later, they were returned to the chambers for a “cue test”, in which responses on the previously reward-associated lever triggered cue presentation, but no contingent reward. We used this model to further delineate behavioral and affective changes that accompany increased opioid craving in late abstinence, as well as molecular alterations underlying craving in rats that did not undergo a cue test. We found an opioid-specific behavioral signature in which peak opioid craving is accompanied by decreased grooming and hyperactivity in both sexes. We tracked the female estrous cycle throughout, as these fluctuations in reproductive hormones (akin to the menstrual cycle) are shown to affect cocaine- and nicotine-related behaviors. We found no differences between females in different phases of the estrous cycle in terms of self-administration, nor craving. RNA sequencing of the nucleus accumbens shell revealed robust changes in gene expression that occurred across extended abstinence, though the genes themselves were altered in a sex- and reinforcer-specific manner. In general, we found many behavioral and molecular changes that were unique to sex and reinforcer (sucrose versus opioids). This is promising in terms of identifying opioid-specific targets that are unlikely to affect the natural reward system in both sexes. Changes in gene expression in the brain are mediated in part by epigenetic processes that influence access of transcriptional machinery to DNA. Acetylation of histone tails, the proteins around which DNA is wrapped and packaged in the nucleus, have been identified as permissive marks that facilitate long-lasting changes in transcriptomics in response to environmental insults. Opioids promote increased acetylation, which may contribute to some of the reported changes here. We tested the efficacy of JQ1, a treatment that interferes with the read-out of opioid-induced acetylated marks, at attenuating heroin self-administration. When administered as an intracerebroventricular microinjection on self-administration day 11, JQ1 had no effect on subsequent heroin taking in either sex, suggesting that it may not be suitable as a systemic treatment at the dose given. These studies lay the groundwork for future studies to administer other treatments throughout abstinence, based on the opioid-specific genes and pathways identified here, to reduce cue-induced heroin craving and the accompanying suite of behaviors in males and females. / Psychology

No description available.

No description available.

AML is a cancer of the blood and bone marrow characterized by the presence of highly proliferative and abnormally differentiated myeloblasts. Previous work from the Bhatia lab utilized the orthotopic xenograft model in order to isolate a population of leukemic regenerating cells (LRC) that exists prior to relapse. Affymatrix analysis of LRCs revealed up-regulation of 248 genes that can act as unique targets to prevent relapse. In order to screen compounds against all 248 targets, it is important to develop an in vitro model that is able to appropriately recapture the functional and molecular markers of LRCs. Primary AML samples were treated with 5-doses of 0.15 μM, 1 μM AraC, or DMSO control and several outcomes were measured. In vitro AraC treatment was not able to recapitulate the progenitor frequency curve and CD34 expression curve observed in vivo. Additionally, we were not able to see a consistent increase in select LRC targets DRD2, GLUT2, FUT3, and FASL via flow cytometry. Despite an increase in the mRNA levels of LRC genes 24h after treatment with 0.15 μM AraC, long term analysis could not be completed due to poor RNA quality and low expression of LRC-targets. Primary AML cells were co-culture with mouse MS-5 stromal cell line order to study the effects of mesenchymal stromal cells on AML response to AraC. Co-culture with MS-5 cells had different effects on select primary AML cells. AML 14939 showed an increase in CD34 and LRC targets DRD2 and FUT3 following AraC treatment when co-cultured with MS-5 cells; while A374 showed no differences between DMSO and AraC treated groups. Overall, these findings suggest the LRC signature is not induced by treatment with AraC alone. Complex interactions between AML cells and their bone marrow niche during AraC treatment plays an important role in the development of LRCs prior to AML relapse. / Thesis / Master of Science (MSc) / AML is a cancer of blood cells characterized by the presence of rapidly dividing cancer cells termed myeloblasts. AML has a high rate of disease relapse. The Bhatia lab modelled AML relapse in a mouse and discovered an unique population of cells that exist prior to relapse termed LRCs. LRCs express distinctive genes that can act as targets for the development of new therapies to prevent relapse. In order to screen potential relapse preventing compounds, we set out to recapture AML relapse using cells in a dish. AML cells from patients were treated with chemotherapy reagent AraC and the number of cancer progenitors and the expression of specific LRC proteins were measured. AraC did not increase the level of 3 out of 4 LRC proteins studied. We determined the LRCs were not caused by AraC treatment, and the physiology of the bone marrow environment plays an important role in inducing relapse.

Yes / Background. Increased availability of Next Generation Sequencing (NGS) techniques allows, for the first time, to distinguish relapses from reinfections in patients with multiple Buruli ulcer (BU) episodes. Methodology. We compared the number and location of single nucleotide polymorphisms (SNPs) identified by genomic screening between four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence, derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin. Principal Findings. The findings suggest that after surgical treatment—without antibiotics—the second episodes were due to relapse rather than reinfection. Since specific antibiotics were introduced for the treatment of BU, the one patient with a culture available from both disease episodes had M. ulcerans isolates with a genomic distance of 20 SNPs, suggesting the patient was most likely reinfected rather than having a relapse. Conclusions. To our knowledge, this study is the first to study recurrences in M. ulcerans using NGS, and to identify exogenous reinfection as causing a recurrence of BU. The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development. / This work was supported by the UBS Optimus Foundation (Zurich, Switzerland) and the Department of Economy, Science and Innovation of the Flemish Government (Belgium). KV was supported by a VLADOC PhD scholarship of VLIRUOS (Belgium).

Graphs (or networks) are now omnipresent, infusing into many aspects of society. This dissertation contributes unified graph-based algorithms and models to help solve large-scale societal problems affecting millions of individuals' daily lives, from cyber-attacks involving malware to tobacco and alcohol addiction. The main thrusts of our research are: (1) Propagation-based Graph Mining Algorithms: We develop graph mining algorithms to propagate information between the nodes to infer important details about the unknown nodes. We present three examples: AESOP (patented) unearths malware lurking in people's computers with 99.61% true positive rate at 0.01% false positive rate; our application of ADAGE on malware detection (patent-pending) enables to detect malware in a streaming setting; and EDOCS (patent-pending) flags comment spammers among 197 thousand users on a social media platform accurately and preemptively. (2) Graph-induced Behavior Characterization: We derive new insights and knowledge that characterize certain behavior from graphs using statistical and algorithmic techniques. We present two examples: a study on identifying attributes of smoking and drinking abstinence and relapse from an addiction cessation social media community; and an exploratory analysis of how company insiders trade. Our work has already made impact to society: deployed by Symantec, AESOP is protecting over 120 million people worldwide from malware; EDOCS has been deployed by Yahoo and it guards multiple online communities from comment spammers.