Rx for addiction and medication safety: An evaluation of teen education for opioid misuse prevention

Background: Rhode Island (RI) ninth graders report lifetime nonmedical use of prescription opioids (NMUPO) of 8.9%. NMUPO is associated with transition to heroin use, opioid overdose, and death. Objectives: Measure changes in 9th grade students\u27 knowledge, confidence, perceptions of opioid use disorder prevention, overdose response with naloxone, treatment, and recovery, following the delivery of an interactive substance use disorder curriculum. Methods: Eight RI public high schools were recruited to participate. Freshman in each school were administered identical surveys that collected demographic data, substance use and misuse knowledge, students\u27 perceptions of substance misuse harm, reported drug use, and risk and protective behaviors before and after the curriculum. Results: Among 969 pre-intervention survey respondents, 19% reported use of marijuana, 3% heroin use, and 21% nonmedical use of prescription opioids. Between the pre-intervention to the post-intervention survey, significantly more students identified that addiction is a chronic brain disease (79%–83%, p = 0.05), drug users are not responsible for their addiction (81%–88%, p = 0.001), and that non-medical use of a prescription medication is use without a prescription (81%–88%, p = 0.001). Improved confidence was also reported in identifying opioid withdrawal symptoms (26%–45%, p \u3c 0.0001), identifying signs of an opioid overdose from 29% to 46% (p \u3c 0.0001), and knowing when to administer naloxone (17%–45%, p \u3c 0.0001). Confidence to refer someone to treatment improved from 31% to 45% (p \u3c 0.0001). Logistic regression showed associations between mental health, peer use, parental affection, and academic performance factors as related to NMUPO. Conclusions: Students reported significant NMUPO prevalence. Ninth grade students\u27 knowledge and confidence of opioid misuse, overdose response, and recovery resources increased following the delivery of a multi-modal interactive substance use disorder curriculum. Community, school, and student-level interventions are needed to reduce NMUPO

Dnmt3a restrains mast cell inflammatory responses

DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in DNMT3A correlate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to acute and chronic stimuli, both in vitro and in vivo. The exacerbated mast cell responses observed in the absence of Dnmt3a were recapitulated or enhanced by treatment with the demethylating agent 5-aza-2′-deoxycytidine as well as by down-modulation of Dnmt1 expression, further supporting the role of DNA methylation in regulating mast cell activation. Mechanistically, these effects were in part mediated by the dysregulated expression of the scaffold protein IQGAP2, which is characterized by the ability to regulate a wide variety of biological processes. Altogether, our data demonstrate that DNMT3A and DNA methylation are key modulators of mast cell responsiveness to acute and chronic stimulation

Identification and Description of Potentially Influential Social Network Members using the Strategic Player Approach

Background: Diffusion of innovations theory posits that ideas and behaviors can be spread through social network ties. In intervention work, intervening upon certain network members may lead to intervention effects “diffusing” into the network to affect the behavior of network members who did not receive the intervention. The strategic players (SP) method, an extension of Borgatti’s Key Players approach, is used to balance the (sometimes) opposing goals of spreading the intervention to as many members of the target group as possible, while preventing the spread of the intervention to others. Objectives: We sought to test whether members of the SP set have network position and non-network differences (such as demographic, attitudinal, or behavioral differences) compared to the remaining members of the target group (non-SPs). Methods: A first-year class at a private residential university (N = 1342) completed network and non-network measures. Analyses were restricted only to heavy drinkers, leading to a final analytic sample of 529. Results: SPs and non-SPs differed on multiple network variables, but did not differ on most demographic, attitudinal, and behavior variables. Conclusions: As designed, the SP program identified participants who were distinguished by their network position. The fact that they did not also differ on other characteristics shows the SPs are not significantly different than heavy drinkers who were not selected

Attempts at memory control induce dysfunctional brain activation profiles in Generalized Anxiety Disorder: An exploratory fMRI study

Suppression of aversive memories through memory control has historically been proposed as a central psychological defense mechanism. Inability to suppress memories is considered a central psychological trait in several psychiatric disorders, including Generalized Anxiety Disorder (GAD). Yet, few studies have attempted the focused identification of dysfunctional brain activation profiles when patients with Generalized Anxiety Disorders attempt memory control. Using a well-characterized behavioral paradigm we studied brain activation profiles in a group of adult GAD patients and well-matched healthy controls (HC). Participants learned word-association pairs before imaging. During fMRI when presented with one word of the pair, they were instructed to either suppress memory of, or retrieve the paired word. Subsequent behavioral testing indicated both GAD and HC were able to engage in the task, but attempts at memory control (suppression or retrieval) during fMRI revealed vastly different activation profiles. GAD were characterized by substantive hypo-activation signatures during both types of memory control, with effects particularly strong during suppression in brain regions including the dorsal anterior cingulate and the ventral prefrontal cortex. Attempts at memory control in GAD fail to engage brain regions to the same extent HC, providing a putative neuronal signature for a well-established psychological characteristic of the illness

Resistance to Peer influence Moderates the Relationship Between Perceived (But Not Actual) Peer Norms and Binge Drinking in a College Student Social Network

Introduction: Adolescent and young adult binge drinking is strongly associated with perceived social norms and the drinking behavior that occurs within peer networks. The extent to which an individual is influenced by the behavior of others may depend upon that individual’s resistance to peer influence (RPI). Methods: Students in their first semester of college (N = 1323; 54.7% female, 57% White, 15.1% Hispanic) reported on their own binge drinking, and the perceived binge drinking of up to 10 important peers in the first-year class. Using network autocorrelation models, we investigated cross-sectional relationships between participant’s binge drinking frequency and the perceived and actual binge drinking frequency of important peers. We then tested the moderating role of RPI, expecting that greater RPI would weaken the relationship between perceived and actual peer binge drinking on participant binge drinking. Results: Perceived and actual peer binge drinking were statistically significant predictors of participant binge drinking frequency in the past month, after controlling for covariates. RPI significantly moderated the association between perceptions of peer binge drinking and participant’s own binge drinking; this association was weaker among participants with higher RPI compared to those with lower RPI. RPI did not interact with the actual binge drinking behavior of network peers

An Event- and Network-Level Analysis of College Students’ Maximum Drinking Day

Background—Heavy episodic drinking is common among college students and remains a serious public health issue. Previous event-level research among college students has examined behaviors and individual-level characteristics that drive consumption and related consequences but often ignores the social network of people with whom these heavy drinking episodes occur. The main aim of the current study was to investigate the network of social connections between drinkers on their heaviest drinking occasions. Methods—Sociocentric network methods were used to collect information from individuals in the first-year class (N=1342) at one university. Past-month drinkers (N=972) reported on the characteristics of their heaviest drinking occasion in the past month and indicated who else among their network ties was present during this occasion. Results—Average max drinking day indegree, or the total number of times a participant was nominated as being present on another students’ heaviest drinking occasion, was 2.50 (SD = 2.05). Network autocorrelation models indicated that max drinking day indegree (e.g., popularity on heaviest drinking occassions) and peers’ number of drinks on their own maximum drinking occasions were significantly associated with participant maximum number of drinks, after controlling for demographic variables, pregaming, and global network indegree (e.g., popularity in the entire first-year class). Conclusion—Being present at other peers’ heaviest drinking occasions is associated with greater drinking quantities on one’s own heaviest drinking occasion. These findings suggest the potential for interventions that target peer influences within close social networks of drinkers

Enrollment and Assessment of a First-Year College Class Social Network for a Controlled Trial of the Indirect Effect of a Brief Motivational Intervention

Heavy drinking and its consequences among college students represent a serious public health problem, and peer social networks are a robust predictor of drinking-related risk behaviors. In a recent trial, we administered a Brief Motivational Intervention (BMI) to a small number of first-year college students to assess the indirect effects of the intervention on peers not receiving the intervention. Objectives: To present the research design, describe the methods used to successfully enroll a high proportion of a first-year college class network, and document participant characteristics. Methods: Prior to study enrollment, we consulted with a student advisory group and campus stakeholders to aid in the development of study-related procedures. Enrollment and baseline procedures were completed in the first six weeks of the academic semester. Surveys assessed demographics, alcohol use, and social network ties. Individuals were assigned to a BMI or control group according to their dormitory location. Results: The majority of incoming first-year students (1342/1660; 81%) were enrolled (55% female, 52% nonwhite, mean age 18.6 [SD = 0.51]). Differences between the intervention and control group were noted in alcohol use, but were in large part a function of there being more substance-free dormitory floors in the control group. Conclusions: The current study was successful in enrolling a large proportion of a first-year college class and can serve as a template for social network investigations

Common and different neural markers in major depression and anxiety disorders: A pilot structural magnetic resonance imaging study.

Although anxiety and depression often co-occur and share some clinical features, it is still unclear if they are neurobiologically distinct or similar processes. In this study, we explored common and specific cortical morphology alterations in depression and anxiety disorders. Magnetic Resonance Imaging data were acquired from 13 Major Depressive Disorder (MDD), 11 Generalized Anxiety Disorder (GAD), 11 Panic Disorder (PD) patients and 21 healthy controls (HC). Regional cortical thickness, surface area (SA), volume and gyrification were measured and compared among groups. We found left orbitofrontal thinning in all patient groups, as well as disease-specific alterations. MDD showed volume deficits in left precentral gyrus compared to all groups, volume and area deficits in right fusiform gyrus compared to GAD and HC. GAD showed lower SA than MDD and PD in right superior parietal cortex, higher gyrification than HC in right frontal gyrus. PD showed higher gyrification in left superior parietal cortex when compared to MDD and higher SA in left postcentral gyrus compared to all groups. Our results suggest that clinical phenotypic similarities between major depression and anxiety disorders might rely on common prefrontal alterations. Frontotemporal and parietal abnormalities may represent unique biological signatures of depression and anxiety

Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis

Background Natural killer cells are involved in the complex mechanisms underlying autoimmune diseases but few studies have investigated their role in autoimmune hepatitis. Killer immunoglobulin-like receptors are key regulators of natural killer cell-mediated immune responses. Methods and Findings KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 114 patients diagnosed with type 1 autoimmune hepatitis and compared with a group of 221 healthy controls. HLA Class I and Class II antigen frequencies were compared to those of 551 healthy unrelated families representative of the Sardinian population. In our cohort, type 1 autoimmune hepatitis was strongly associated with the HLA-B18, Cw5, DR3 haplotype. The KIR2DS1 activating KIR gene and the high affinity HLA-C2 ligands were significantly higher in patients compared to controls. Patients also had a reduced frequency of HLA-Bw4 ligands for KIR3DL1 and HLA-C1 ligands for KIR2DL3. Age at onset was significantly associated with the KIR2DS1 activating gene but not with HLA-C1 or HLA-C2 ligand groups. Conclusions The activating KIR gene KIR2DS1 resulted to have an important predictive potential for early onset of type 1 autoimmune hepatitis. Additionally, the low frequency of the KIR-ligand combinations KIR3DL1/HLA-Bw4 and KIR2DL3/HLA-C1 coupled to the high frequency of the HLA-C2 high affinity ligands for KIR2DS1 could contribute to unwanted NK cell autoreactivity in AIH-1

Comparison of two strategies for the management of postoperative recurrence in Crohn's disease patients with one clinical risk factor: A multicentre IG-IBD study

BackgroundThe management of postoperative recurrence (POR) in Crohn's disease (CD) after ileo-colonic resection is a highly debated topic. Prophylactic immunosuppression after surgery is currently recommended in the presence of at least one clinical risk factor. ObjectiveOur aim was to determine whether early immunosuppression can be avoided and guided by endoscopy in CD patients with only one risk factor. MethodsCD patients with only one risk factor for POR, including previous intestinal resection, extensive small intestine resection (>50 cm), fistulising phenotype, history of perianal disease, and active smoking, were retrospectively included. Two groups were formed based on whether immunosuppression was started immediately after surgery ("prophylaxis group") or guided by endoscopy ("endoscopy-driven group"). Primary endpoints were rates of any endoscopic recurrence (Rutgeerts >= i2a) and severe endoscopic recurrence (i4) within 12 months after surgery. Secondary outcomes were clinical recurrence rates at 6, 12 and 24 months after surgery. ResultsA total of 195 patients were enroled, of whom 61 (31.3%) received immunoprophylaxis. No differences between immunoprophylaxis and the endoscopy-driven approach were found regarding any endoscopic recurrence (36.1% vs. 45.5%, respectively, p = 0.10) and severe endoscopic recurrence (9.8% vs. 15.7%, respectively, p = 0.15) at the first endoscopic evaluation. Clinical recurrence rates were also not statistically different (p = 0.43, p = 0.09, and p = 0.63 at 6, 12, and 24 months, respectively). ConclusionsIn operated CD patients with only one risk factor for POR, immediate immunoprophylaxis does not decrease the rate of early clinical and endoscopic recurrence. Prospective studies are needed to confirm our results