ItemIndividual Development Plan (IDP) for IUPUI PREP Fellows [Template](IUPUI IPREP, 2017) Bahamonde, RafaelThis is an Individual Development Plan (IDP) is a planning tool designed to help IUPUI Post-Baccalaureate Research Education Program (IPREP) Fellows identify annual progress, professional development needs, and career objectives. The IDP also serves as a valuable communication tool between the IPREP Fellows and their research Mentors. The information in the IDP was the result of evaluation of multiple IDP from other universities to create an IDP to work with the IPREP fellows and mentors. ItemQuantifying Behavioral Sensation Seeking With the Aroma Choice Task(SAGE, 2019-07-27) Oberlin, Brandon G.; Ramer, Nolan E.; Bates, Sage M.; Shen, Yitong I.; Myslinski, Jeremy S.; Kareken, David A.; Cyders, Melissa A.; Psychiatry, School of MedicineOur goal was to develop a behavioral measure of sensation seeking (SS). The Aroma Choice Task (ACT) assesses preference for an intense, novel, varied, and risky (exciting) option versus a mild, safe (boring) option using real-time odorant delivery. A total of 147 healthy young adults completed 40 binary choice trials. We examined (1) intensity and pleasantness of odorants, (2) stability of responding, (3) association with SS self-report, and (4) association with self-reported illicit drug use. Participants’ preference for the “exciting” option versus the safe option was significantly associated with self-reported SS (p < .001) and illicit drug use (p = .041). Odorant ratings comported with their intended intensity. The ACT showed good internal, convergent, and criterion validity. We propose that the ACT might permit more objective SS assessment for investigating the biological bases of psychiatric conditions marked by high SS, particularly addiction. The ACT measures SS behaviorally, mitigating some self-report challenges and enabling real-time assessment, for example, for functional magnetic resonance imaging (fMRI). ItemAssessment of Acute Motor Effects and Tolerance Following Self‐Administration of Alcohol and Edible ∆9‐Tetrahydrocannabinol in Adolescent Male Mice(Wiley, 2019-11) Smoker, Michael P.; Hernandez, Maribel; Zhang, Yanping; Boehm, Stephen L., II; Psychology, School of ScienceBackground Cannabinoids and their principle psychoactive target, the cannabinoid type 1 receptor (CB1R), impact a number of alcohol‐related properties, and although alcohol and cannabis are often co‐used, particularly in adolescence, few animal models of this phenomenon exist. We modeled the co‐use of alcohol and ∆9‐tetrahydrocannabinol (THC) in adolescent mice using ingestive methods popular during this developmental period in humans, namely binge‐drinking and edible THC. With this model, we assessed levels of use, acute effects, and tolerance to each substance. Methods Adolescent male C57BL/6J mice had daily, limited access to 1 of 2 edible doughs (THC or control), to 1 of 2 fluids (ethanol (EtOH) or water), and in 1 of 2 orders (dough–fluid or fluid–dough). Home cage locomotor activity was recorded both during access and after access. On the day following the final access session, a subset of mice were assessed for functional and metabolic tolerance to alcohol using accelerating rotarod and blood EtOH concentrations, respectively. The remaining mice were assessed for tolerance to THC‐induced hypothermia, and whole‐brain CB1R expression was assessed in all mice. Results EtOH intake was on par with levels previously reported in adolescent mice. Edible THC was well‐consumed, but consumption decreased at the highest dose provided. Locomotor activity increased following EtOH intake and decreased following edible THC consumption, and edible THC increased fluid intake in general. The use of alcohol produced neither functional nor metabolic tolerance to an alcohol challenge. However, the use of edible THC impaired subsequent drug‐free rotarod performance and was associated with a reduction in THC's hypothermic effect. Conclusions Adolescent mice self‐administered both alcohol and edible THC to a degree sufficient to acutely impact locomotor activity. However, only edible THC consumption had lasting effects during short‐term abstinence. Thus, this adolescent co‐use model could be used to explore sex differences in self‐administration and the impact substance co‐use might have on other domains such as mood and cognition. ItemShared Neural Correlates Underlying Addictive Disorders and Negative Urgency(MDPI, 2019-02-08) Um, Miji; Whitt, Zachary T.; Revilla, Rebecca; Hunton, Taylor; Cyders, Melissa A.; Department of Psychology, School of ScienceNegative urgency is a personality trait reflecting the tendency to act rashly in response to extreme negative emotions and is considered a transdiagnostic endophenotype for problematic levels of addictive behaviors. Recent research has begun to identify the neural correlates of negative urgency, many of which appear to overlap with neural circuitry underlying addictive disorders associated with negative urgency. The goal of this qualitative review is to summarize the extant literature concerning the neural correlates of negative urgency, to compare these correlates with those implicated with addictive disorders, and to propose new ways to begin to leverage such findings in treatment and intervention approaches. We also address current limitations in the field and make recommendations for areas for future growth in this research domain. Patterns of structure and function in the ventral striatum, frontal regions, such as the prefrontal cortex (PFC) and orbitofrontal cortex (OFC), and amygdala are common across addictive disorders and are related to both real-world risky behaviors and self-report measures of negative urgency. We propose that the time has come to move past considering this trait and these disorders as completely separate entities, and instead for the field to consider how general patterns of convergence across these disorders can lead to a more transdiagnostic approach to treatment and intervention. We suggest future work utilize these convergent patterns in the development of animal models of negative urgency, in the identification and testing of prime pharmacological and physiological interventions, and as objective biomarkers to be used when testing behavioral, pharmacological, and physiological intervention effectiveness. Little empirical work has been done to date in these areas and advances in these nascent fields would advance understanding and applications of the neuroscience of negative urgency. ItemZoledronate and Raloxifene combination therapy enhances material and mechanical properties of diseased mouse bone(Elsevier, 2019-10) Powell, Katherine M.; Skaggs, Cayla; Pulliam, Alexis; Berman, Alycia; Allen, Matthew R.; Wallace, Joseph M.; Biomedical Engineering, School of Engineering and TechnologyCurrent interventions to reduce skeletal fragility are insufficient at enhancing both the quantity and quality of bone when attempting to improve overall mechanical integrity. Bisphosphonates, such as Zoledronate (ZOL), are used to treat a variety of bone disorders by increasing bone mass to decrease fracture risk, but long-term use has been shown in some settings to compromise bone quality. Alternatively, Raloxifene (RAL) has recently been demonstrated to improve tissue quality and overall mechanical properties in a cell-independent manner by binding to collagen and increasing tissue hydration. We hypothesized that a combination of RAL and ZOL would improve mechanical and material properties of bone more than either monotherapy alone by enhancing both quantity and quality. In this study, wildtype (WT) and heterozygous (OIM+/−) male mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL, ZOL, or both from 8 weeks to 16 weeks of age. Using the OIM model allows for investigation of therapeutic effects on a quality-based bone disease. Combination treatment resulted in higher trabecular architecture, cortical mechanical properties, and cortical fracture toughness in diseased mouse bone. Two fracture toughness properties, which are direct measures of the tissue's ability to resist the initiation and propagation of a crack, were significantly improved with combination treatment in OIM+/− compared to control. There was no significant effect on fracture toughness with either monotherapy alone in either genotype. Following the mass-based effects of ZOL, trabecular bone volume fraction was significantly higher with combination treatment in both genotypes. Combination treatment resulted in higher ultimate stress in both genotypes. RAL and combination treatment in OIM+/− also increased resilience compared to the control. In conclusion, this study demonstrates the beneficial effects of using combination drug treatments to increase bone mass while simultaneously improving tissue quality, especially to enhance the mechanical integrity of diseased bone. Combination therapies could be a potential method to improve bone health and combat skeletal fragility on both the microscopic and macroscopic levels. ItemPredicting running away in girls who are victims of commercial sexual exploitation(Elsevier, 2018-05) Hershberger, Alexandra R.; Sanders, Jasmyn; Chick, Crisanna; Jessup, Megan; Hanlin, Hugh; Cyders, Melissa A.; Psychology, School of ScienceYouth that are victims of commercial sexual exploitation of children (CSEC) have a host of clinical problems and often run away from home, residential care, and treatment, which complicates and limits treatment effectiveness. No research to date has attempted to predict running away in CSEC victims. The present study aimed to 1) characterize a clinically referred sample of girls who were victims of CSEC and compare them to other high-risk girls (i.e., girls who also have a history of trauma and running away, but deny CSEC); and 2) examine the utility of using the Youth Level of Service/Case Management Inventory (YLS/CMI) to predict future running away. Data were collected from de-identified charts of 80 girls (mean age = 15.38, SD = 1.3, 37.9% White, 52.5% CSEC victims) who were referred for psychological assessment by the Department of Child Services. Girls in the CSEC group were more likely to have experienced sexual abuse (χ2 = 6.85, p = .009), an STI (χ2 = 6.45, p = .01), a post-traumatic stress disorder diagnosis (χ2 = 11.84, p = .001), and a substance use disorder diagnosis (χ2 = 11.32, p = .001) than high-risk girls. Moderated regression results indicated that YLS/CMI scores significantly predicted future running away among the CSEC group (β = 0.23, SE = .06, p = .02), but not the high-risk group (β = -.008, SE = .11, p =.90). The YLS/CMI shows initial promise for predicting future running away in girls who are CSEC victims. Predicting running away can help identify those at risk for and prevent running away and improve treatment outcomes. We hope current findings stimulate future work in this area. ItemPTSD Symptoms Mediate the Relationship Between Sexual Abuse and Substance Use Risk in Juvenile Justice-Involved Youth(Sage, 2018-08) Sanders, Jasmyn; Hershberger, Alexandra R.; Kolp, Haley M.; Um, Miji; Aalsma, Matthew; Cyders, Melissa A.; Pediatrics, School of MedicineJuvenile justice-involved youth face disproportionate rates of sexual abuse, which increases the risk of post-traumatic stress disorder (PTSD) and substance use disorders (SUDs), both of which are associated with poor long-term outcomes. The present study tested two mediation and moderation models, controlling for age, race, and history of physical abuse, with gender as a moderator, to determine whether PTSD symptoms serve as a risk factor and/or mechanism in the relationship between sexual abuse and substance use. Data were examined for 197 juvenile justice-involved youth (mean age = 15.45, 68.9% non-White, 78.4% male) that completed court-ordered psychological assessments. Results indicated that PTSD symptoms significantly mediated the relationship between sexual abuse and drug (β = 3.44, confidence interval [CI] [0.26, 7.41]; test for indirect effect z = 2.41, p = .02) and alcohol use (β = 1.42, CI [0.20, 3.46]; test for indirect effect z = 2.23, p = .03). PTSD symptoms and gender were not significant moderators. Overall, PTSD symptoms mediate the relationship between sexual abuse and SUDs in juvenile justice-involved youth, which suggests viability of targeting PTSD symptoms as a modifiable risk factor to reduce the effects of sexual abuse on substance use in this high-risk population. ItemConduct disorder symptoms and illicit drug use in juvenile justice involved youth: The reciprocal relationship between positive illicit drug use attitudes and illicit drug use(Taylor & Francis, 2018-07-03) Kolp, Haley M.; Hershberger, Alexandra R.; Sanders, Jasmyn; Um, Miji; Aalsma, Matthew; Cyders, Melissa A.; Psychology, School of ScienceConduct disorder (CD) symptoms cooccur at high rates with illicit drug use in juvenile justice involved youth, which results in poorer outcomes; however, research has not identified where best to intervene in this relationship, limiting the identification of modifiable risk factors to reduce negative effects of CD symptoms. Two mediation models were examined to investigate the potential for CD symptoms to influence a reciprocal relationship between illicit drug use and positive drug attitudes, controlling for age, gender, and race. Data were examined for 245 juvenile justice involved youth (mean age = 15.46, SD = 1.30, range 12-18, 64.9% Black, 80.4% male) who completed court-ordered psychological assessments. Findings indicate: (1) Positive attitudes toward illicit drug use significantly mediated the relationship between CD symptoms and illicit drug use (β = 0.16, CI 0.09-0.27; test for indirect effect z = 4.17, p < .001) and (2) illicit drug use significantly mediated the relationship between CD symptoms and positive attitudes toward illicit drug use (β = 0.20, CI 0.12-0.32; test for indirect effect z = 4.87, p < .001). Overall, the present study suggests that CD symptoms impart risk for illicit drug use both indirectly, through more positive attitudes toward illicit drug use, and directly, which further strengthens positive attitudes toward illicit drug use. ItemEnzymatic Cross-Linking of Dynamic Thiol-Norbornene Click Hydrogels(ACS, 2019) Nguyen, Han D.; Liu, Hung-Yi; Hudson, Britney N.; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and TechnologyEnzyme-mediated in situ forming hydrogels are attractive for many biomedical applications because gelation afforded by enzymatic reactions can be readily controlled not only by tuning macromer compositions, but also by adjusting enzyme kinetics. For example, horseradish peroxidase (HRP) has been used extensively for in situ cross-linking of macromers containing hydroxyl-phenol groups. The use of HRP to initiate thiol-allylether polymerization has also been reported, yet no prior study has demonstrated enzymatic initiation of thiol-norbornene gelation. In this study, we discovered that HRP can generate the thiyl radicals needed for initiating thiol-norbornene hydrogelation, which has only been demonstrated previously using photopolymerization. Enzymatic thiol-norbornene gelation not only overcomes light attenuation issue commonly observed in photopolymerized hydrogels, but also preserves modularity of the cross-linking. In particular, we prepared modular hydrogels from two sets of norbornene-modified macromers, 8-arm poly(ethylene glycol)-norbornene (PEG8NB) and gelatin-norbornene (GelNB). Bis-cysteine-containing peptides or PEG-tetra-thiol (PEG4SH) was used as a cross-linker for forming enzymatically and orthogonally polymerized hydrogel. For HRP-initiated PEG-peptide hydrogel cross-linking, gelation efficiency was significantly improved via adding tyrosine residues on the peptide cross-linkers. Interestingly, these additional tyrosine residues did not form permanent dityrosine cross-links following HRP-induced gelation. As a result, they remained available for tyrosinase-mediated secondary cross-linking, which dynamically increased hydrogel stiffness. In addition to material characterizations, we also found that both PEG- and gelatin-based hydrogels exhibited excellent cytocompatibility for dynamic 3D cell culture. The enzymatic thiol-norbornene gelation scheme presented here offers a new cross-linking mechanism for preparing modularly and dynamically cross-linked hydrogels. ItemElectroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells(Wiley, 2017-05) Salazar, Tatiana E.; Richardson, Matthew R.; Beli, Eleni; Ripsch, Matthew S.; George, John; Kim, Youngsook; Duan, Yaqian; Moldovan, Leni; Yan, Yuanqing; Bhatwadekar, Ashay; Jadhav, Vaishnavi; Smith, Jared A.; McGorray, Susan; Bertone, Alicia L.; Traktuev, Dmitri O.; March, Keith L.; Colon-Perez, Luis M.; Avin, Keith; Sims, Emily; Mund, Julie A.; Case, Jamie; Deng, Shaolin; Kim, Min Su; McDavitt, Bruce; Boulton, Michael E.; Thinschmidt, Jeffrey; Calzi, Sergio Li; Fitz, Stephanie D.; Fuchs, Robyn K.; Warden, Stuart J.; McKinley, Todd; Shekhar, Anantha; Febo, Marcelo; Johnson, Phillip L.; Chang, Lung Ji; Gao, Zhanguo; Kolonin, Mikhail G.; Lai, Song; Ma, Jinfeng; Dong, Xinzhong; White, Fletcher A.; Xie, Huisheng; Yoder, Mervin C.; Grant, Maria B.; Ophthalmology, School of MedicineElectroacupuncture (EA) performed in rats and humans using limb acupuncture sites, LI-4 and LI-11, and GV-14 and GV-20 (humans) and Bai-hui (rats) increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSCs) into the systemic circulation. In human subjects, the source of the MSC was found to be primarily adipose tissue, whereas in rodents the tissue sources were considered more heterogeneous. Pharmacological disinhibition of rat hypothalamus enhanced sympathetic nervous system (SNS) activation and similarly resulted in a release of MSC into the circulation. EA-mediated SNS activation was further supported by browning of white adipose tissue in rats. EA treatment of rats undergoing partial rupture of the Achilles tendon resulted in reduced mechanical hyperalgesia, increased serum interleukin-10 levels and tendon remodeling, effects blocked in propranolol-treated rodents. To distinguish the afferent role of the peripheral nervous system, phosphoinositide-interacting regulator of transient receptor potential channels (Pirt)-GCaMP3 (genetically encoded calcium sensor) mice were treated with EA acupuncture points, ST-36 and LIV-3, and GV-14 and Bai-hui and resulted in a rapid activation of primary sensory neurons. EA activated sensory ganglia and SNS centers to mediate the release of MSC that can enhance tissue repair, increase anti-inflammatory cytokine production and provide pronounced analgesic relief.