bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats
Authors: Yoshinaga Ryohei , Fukui Tomomi , Yoshifuji Mayuko , Fujimura Mai , Oyama Tatsuya , Oka Michiko
Published: March 2019

Background

Although numerous reports have shown that α1-adrenoceptor (α1-AR) antagonists, which are used to treat benign prostatic hyperplasia (BPH), can cause ejaculatory disorders, few studies have investigated whether the phosphodiesterase 5 (PDE5) inhibitor tadalafil has such adverse effects. In this study, we compared the effects of tadalafil and α1-AR antagonists on seminal emission and their mechanisms of action.

Aim

To evaluate in normal rats the possible effects of tadalafil on spontaneous seminal emission (SSE) and seminal contraction evoked by hypogastric nerve stimulation.

Methods

Male Sprague-Dawley rats were used. To assess SSE, plastic corsets were fitted around the thorax and upper abdomen of male Sprague–Dawley rats to prevent genital autogrooming. Rats were treated orally with tadalafil or an α1-AR antagonist (silodosin, naftopidil, or tamsulosin) for 3 days and housed in wire-bottomed cages. Ejaculatory plugs dropped on the bottoms of the cages were counted and weighed. To assess the intraluminal pressure of seminal vesicles, the hypogastric nerve of urethane-anesthetized rats was isolated and electrically stimulated. After stabilization of seminal vesicle contraction, the rats were intravenously administered test drugs. The expression of PDE5, endothelial nitric oxide synthetase (eNOS), and neuronal NOS (nNOS) in the seminal vesicle and vas deferens were measured by reverse-transcription polymerase chain reaction.

Main Outcome Measure

The number and weight of the ejaculatory plugs produced by corset-fitted rats and the intraluminal pressure of the seminal vesicle were evaluated.

Results

Tadalafil did not affect the number or weight of the ejaculatory plugs of corset-fitted rats, whereas all α1-AR antagonists decreased both in a dose-dependent manner. The α1-AR antagonists, but not tadalafil, inhibited the seminal vesicle contraction evoked by electrical stimulation of the hypogastric nerve. The seminal vesicle and vas deferens expressed higher levels of PDE5 and eNOS mRNA and lower levels of nNOS mRNA relative to the urethra.

Clinical Implications

Tadalafil can be a treatment option in cases where there is concern about negative effects on seminal emission.

Strengths and Limitations

We demonstrated different effects of tadalafil and 3 α1-AR antagonists on rat SSE and their mechanisms of action by measuring seminal vesicle contractility in vivo. A limitation is that we used normal rats, not BPH model rats, and so our results might not apply to human BPH patients.

Conclusion

Tadalafil did not inhibit spontaneous seminal emission or electrical field stimulation–induced seminal vesicle contraction in normal rats. The NO–cyclic guanosine monophosphate pathway is unlikely to be involved in the inhibition of seminal vesicle contraction in normal rats.
3121 Potentially traumatic events and its outcomes among help-seeking adults in Puerto Rico
Authors: Torres Marie , Martinez-Taboas Alfonso , Perez-Pedrogo Coralee , Pena-Orellana Marisol
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: This study aims to evaluate potentially traumatic events (PTEs) and its relationship with posttraumatic stress symptoms (PTSS), posttraumatic growth (PTG), and resilience in a sample of help-seeking individuals in Puerto Rico. METHODS/STUDY POPULATION: This is an analytic, cross sectional design. Adults receiving health services will participate in the study. Recruited participants will provide informed consent during a visit to a community mental health clinic or community hospital. They will complete a demographic document and four retrospective questionnaires about the variables of study. RESULTS/ANTICIPATED RESULTS: We expect that a high rate of potentially traumatic events (PTEs) is associated with an increased rate of posttraumatic stress symptoms (PTSS). We also expect that a high rate of PTSS is associated with an increased rate of posttraumatic growth (PTG). We expect that a high rate of resilience is associated with low rates of PTSS and PTG. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a first step in the development of effective, clearly targeted interventions, specifically designed to treat negative effects, and also to facilitate positive change and resilience after PTE exposure.
3146 Effect of a Junior Faculty Mentoring Program on Confidence in Targeted Academic Skills
Authors: Kitsis Elizabeth , Keller Marla , McGinn Aileen
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to evaluate the effect of a junior faculty mentoring program on change in confidence in key academic skills. METHODS/STUDY POPULATION: The Department of Medicine at the Albert Einstein College of Medicine/Montefiore Medical Center enrolled 33 mentees over three years (2015-2018) in a mentoring program that consisted of monthly interactive seminars focused on topics related to building academic careers, works-in-progress, and pairing of each mentee with a mentor. Mentees were asked about their confidence in key academic skills prior to and after completing the program. Confidence levels were assessed on a seven point scale, ranging from 1 (weak) to 7 (strong). Mean confidence levels were compared between pre and post surveys using independent samples t-test. Matching was not accounted for because not all individuals who completed the pre survey also completed the post survey and vice-versa. Of those mentees who completed both pre and post surveys, confidence scores were analyzed using Wilcoxon matched pairs signed rank test, with similar results to those reported here. Each mentoring session was evaluated by those in attendance at the end of each particular session with possible scores of 1 (unsatisfactory) to 5 (excellent). RESULTS/ANTICIPATED RESULTS: On average the mentees had a fair level of confidence in all nine areas assessed at baseline, with the exception of how to get funding (2.4 ± 1.7). Confidence increased in all areas assessed, and except for how to write a paper (p=.05) all represented a significant increase in confidence (Table 1). Evaluations of each of the mentoring sessions were high, with mean values ranging from 4.3 to 4.9 on the five point scale. DISCUSSION/SIGNIFICANCE OF IMPACT: This mentoring program significantly improved mentees’ confidence in identifying their own professional values and goals, as well as knowing how to turn education into scholarship, work with a mentor, integrate work and life, and give a presentation.
3205 A TL1 Team Approach to Examine Rural Tobacco Users’ Barriers to Participating in Research
Authors: Damiani Rachel Elisabeth , Gebru Neo , Leeman Robert , Krieger Janice
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Our overarching theoretical framework is the health belief model (HBM). Guided by HBM, we aim to identify rural adults’ perceived barriers and motivations to participating in research. Specifically, our research questions are listed below. RQ1: What socio-cultural factors influence rural tobacco users’ intentions to a) participate in research studies and b) undertake tobacco cessation? RQ2: What bio-psychological and behavioral factors influence rural tobacco users’ intentions to a) participate in research studies and b) undertake tobacco cessation? RQ3: How do rural tobacco users perceive citizen scientists as disseminators of a) tobacco cessation and b) recruitment messages? METHODS/STUDY POPULATION: In Phase I of this multi-stage project, we are conducting in-depth interviews with approximately 30 tobacco users in rural Florida. The interview consists of semi-structured questions and multiple validated questionnaires. Specifically, we ask a series of questions about participants’ barriers to participating in research. Additionally, we include questionnaires on participants’ tobacco use history, nicotine dependence, motivation to quit, and willingness to participate in research studies. RESULTS/ANTICIPATED RESULTS: This study consists of two main phases. Data collection for Phase 1 of the study is ongoing, and we will discuss these recent findings. We anticipate data collection and data analysis to be finalized by May, 2019. Beginning in August 2019 through August 2020, we will focus on Phase II, which entails designing and implementing an intervention to increase rural tobacco users’ willingness to participate in research. Given existing literature on other underrepresented groups in research, we anticipate that rural tobacco users will express that logistical barriers, such as transportation and time, prevent them from participating in research. Additionally, we anticipate these individuals may have socio-cultural barriers to participating in research, including distrust in the medical system and apprehension over discipline-specific terminology. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this formative research will be critical to our development of a targeted intervention to increase rural tobacco users’ participation in research. Additionally, our interdisciplinary and community-based approach in this study acknowledges the importance of involving the target population in the research process, which is in line with NIH’s updated model of translational research. We will discuss the process of collaborating with extension agents in rural counties in Florida to reach underrepresented communities.
3548 De novo germline variants in Histone 3 Family 3A (H3F3A) and Histone 3 Family 3B (H3F3B) cause a severe neurodegenerative disorder and functional effects unique from their somatic mutations
Authors: Nair Divya R , Bhoj Elizabeth
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Histones are nuclear proteins that associate with DNA to facilitate packaging into condensed chromatin. Histones are dynamically decorated with post-translational modifications (PTMs), which regulate such processes as DNA repair, gene expression, mitosis, and meiosis. Histone 3 Family 3 (H3F3) histones (H3.3), encoded by H3F3A and H3F3B, mark active genes, maintain epigenetic memory, and maintain heterochromatin and telomeric integrity. Specific somatic mutations in H3F3A and H3F3B have been strongly associated with pediatric glia and other tumors, but no germline mutations have been reported. The goal of our study was to further understand the functional effects of germline mutations of H3F3A and H3F3B. METHODS/STUDY POPULATION: We analyzed 32 patients bearing de novo germline missense mutations in H3F3A or H3F3B with core phenotypes of progressive neurologic dysfunction and congenital anomalies, but no malignancies. Patient histones were analyzed by quantitative mass spectrometry (qMS). RESULTS/ANTICIPATED RESULTS: qMS results revealed that the mutant histone proteins are present at a concentration similar to that of wild-type H3.3. qMS analysis showed strikingly aberrant PTM patterns that suggested local dysregulation. These patterns are distinct from the dominant negative somatic mutations, which cause more global PTM dysregulation. Patient cells also demonstrated upregulation of the expression of genes related to mitosis and cell division, and had a greater proliferative capacity. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggests that the pathogenic mechanism of germline histone mutations is distinct from that of the published cancer-associated somatic histone mutations, but may converge on control of cell proliferation. Further clarification of the pathophysiology in these patients can elucidate the roles of histones and histone PTMs in human development and non-syndromic neurodegeneration. In addition, it provides a framework for targeted therapy development for this and related progressive neurologic disorders.
3496 Mesenchymal Stem Cell Extracellular Vesicle Delivery in a Shear-Thinning Hydrogel For Therapy in an Acute Myocardial Infarction Model: A Comparative Analysis
Authors: Goldberg Drew , Gaffey Ann , Chen Minna , Li Elizabeth , Kim Samuel , Tran Zoe , Burdick Jason , Atluri Pavan
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The primary aim is to assess differences in therapeutic effect between MSC and EPC EVs on acute ischemic rat hearts through delivery in a biocompatible and shear-thinning hydrogel. Primary outcomes for therapeutic assessment include an in-vitro angiogenesis assay and in-vivo hemodynamic analysis, mainly identifying differences in ejection fraction and contractility. Secondary hemodynamic outcomes include cardiac output, stroke volume, and end-diastolic pressure volume relationship (EDPVR). Secondary structural outcomes include post-mortem scar analysis and immunohistochemistry (IHC) staining for angiomyogenesis. METHODS/STUDY POPULATION: MSCs and EPCs will be cultured according to previously published protocols. EVs will be isolated from cultured cell lines through precipitation methods with polyethylene glycol. EVs will be qualitatively analyzed with nanoparticle tracking analysis (NTA) and flow cytometry. The shear thinning hydrogel (STG) will be constructed using a hyaluronic backbone conjugated to adamantane or beta-cyclodextrin, ultimately facilitating guest-host interactions with shear thinning properties. Controls and treatment groups mixed with the hydrogel will be injected into the border zone of infarcted Wistar rat hearts immediately following a left anterior descending artery ligation. Hemodynamic assessment will be performed at four weeks through left ventricular catheter based pressure-volume recordings. Ex-vivo analysis will include scar thickness assessment using Masson collagen staining and IHC stain for vessel (anti-vonWillebrand factor; anti-Isolectin) and myocyte formation (anti-cardiac Troponin I). RESULTS/ANTICIPATED RESULTS: We hypothesize that, in-vitro, MSC-EVs will demonstrate non-inferior angiogenic potential as compared to EPC-EVs. We posit that MSC-EVs will demonstrate superior therapeutic effect to EPC-EVs in-vivo as measured by functional hemodynamics and structural assessment. We have successfully isolated MSC and EPC EVs and have validated uniformity across EV populations (Figure 1). Preliminary data from the angiogenesis assay (n=3) demonstrated that MSC-EV and EPC-EV produce non-significantly different angiogenic potential as measured by number of vascular meshing extremes (p=0.144) and length of master vascular segment (p=0.193), with significant differences compared to either positive or negative controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Novel regenerative therapies are needed for patients with a history of AMI given current limitations to therapy and sequelae of ischemic heart disease. Delivery of extracellular vesicles through a shear-thinning gel is a novel “off-the-shelf” translational approach to address the current clinical need.
3008 Role of Interferon-gamma in Natural Clearance of Chlamydia trachomatis Infection in Women
Authors: Jordan Stephen , Coss Lisa , Wilson Landon , Barnes Stephen , Geisler William , Nelson David
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Chlamydia trachomatis (CT) infection can lead to reproductive morbidity in women. Animal models suggest that protection against CT is mediated through the cytokine interferon-gamma (IFN-γ), produced by CD4+ T-cells, which clears CT through intracellular tryptophan depletion. In humans, correlates of protection remain to be elucidated, which hinders chlamydia vaccine development. Natural clearance of CT infection (e.g., clearance before antibiotics) may be an immunological correlate of protection, evidenced by (1) CT clearance without antibiotics; and (2) a 4-fold reduced risk of CT reinfection within 6 months. We have identified women with and without natural clearance of CT infection. By comparing these two groups of women, the role of IFN-γ-mediated natural clearance of CT infection will be investigated. METHODS/STUDY POPULATION: Through collaboration with a cohort study of CT-infected women, we have access to stored specimens from women who naturally cleared CT or had persisting CT infection. Using peripheral blood mononuclear cell (PBMC), we will assess whether natural clearance of CT infection is associated with IFN-γ-producing CD4+ T-cells by stimulating PBMC ex vivo with CT antigens using intracellular cytokine staining. We will also use cervicovaginal lavage (CVL) and untargeted High-Performance Liquid Chromatography-Mass Spectrometry to assess for tryptophan-dependent and -independent metabolic pathways associated with natural clearance of CT infection. RESULTS/ANTICIPATED RESULTS:: To date, IFN-γ has been measured in 10 women who did not clear CT infection, demonstrating that <20% of these women produced significant levels of IFN-γ. Women who naturally cleared CT have yet to be studied. Untargeted HPLC-MS has been performed on 6 women (3 who cleared matched to 3 with persisting CT infection). To date, 11 pathways that are significantly associated with natural clearance have been identified. DISCUSSION/SIGNIFICANCE OF IMPACT: The outcome of natural clearance of CT infection is distinct from women with persisting chlamydia. These studies may inform whether IFN-γ, produced by CD4+ T-cells, or tryptophan-dependent or -independent metabolic pathways are associated with natural clearance, which may advance chlamydia vaccine development.
3538 Asthma and Depression in Children: the Role of Family Structure
Authors: Shaheen Magda , Teklehaimanot Senait
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Our objective is to examine the relationship between depression, childhood asthma and family structure. METHODS/STUDY POPULATION: We analyzed data from The National Survey of Children’s Health 2011-2012 for the variables family structure, parent’s smoking, education, poverty, available emotional support, and children’s age, gender, race/ethnicity, asthma, physical/mental health, access to care, and insurance. Data were analyzed using multiple logistic regression in STATA 14 (sampling and weight). RESULTS/ANTICIPATED RESULTS: Of the 95,000 participants, 3.8% had depression, 5.1% had anxiety, 8.5% had emotional, developmental, or behavioral problem, 14.6% had asthma and 19% were single-parent family. Asthmatics had higher chance for depression relative to non-asthmatics (Adjusted Odds Ratio (AOR)=1.5, 95% confidence interval (CI)=1.2-1.8), p=0.001). Those living in a single-family home had higher chance for depression than those living in 2-parents homes (AOR=2.5, 95% CI=1.9-3.2), p=0.001). Other predictors were lack of emotional support, age, poverty <100%, poor health, and smoking parent (p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: We concluded that depression was associated with asthma in children from poor single family who lack an emotional support. Management of asthma should include screening and management of psychosocial factors.
3164 Do cancer survivors understand their risk factors for recurrence and the value of coordinated care between an oncologist and a primary care physician? A survey of endometrial and cervical cancer patients
Authors: Sekhon Subhjit , Kuroki Lindsay , Colditz Graham
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: To evaluate gaps in knowledge for women who are cancer survivors regarding the impact of comorbidities and lifestyle behaviors on endometrial and cervical cancer risk, and to assess prevalence of established care with a primary care physician (PCP) among patients and evaluate acceptability of referral to a PCP METHODS/STUDY POPULATION: Single institution cross-sectional study examining all women aged 18 or older with a diagnosis of cervical or endometrial cancer who present for care by a gynecologic oncologist at Barnes-Jewish Hospital/Washington University in St. Louis School of Medicine. Patients will be invited to complete a survey specific to cancer diagnosis that includes questions on participant background and sociodemographic information, knowledge of risk factors for their specific cancer site, and whether or not the patient has a primary care provider and the acceptability of referring RESULTS/ANTICIPATED RESULTS: Majority of women will be unaware of how comorbidities affect cancer risk and treatment outcomes. For women without a PCP, we anticipate that they will be accepting towards the notion of being referred to one for establishing care. DISCUSSION/SIGNIFICANCE OF IMPACT: Pilot information from this study will 1. Allow providers to improve cancer survivorship care plans by increasing collaboration between PCPs and oncologists to provide ongoing care, and 2. Afford information for providers on where gaps in knowledge exist so as to better education patients.
3359 A TL1 Team Approach to Clinician Perspectives on Hoarding Disorder
Authors: Henderson Rebecca R , Cooke Danielle Laine , Archer Christian , McNamara Joseph P. , Collings Pete , Mathews Carol
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: By combining clinical knowledge of hoarding disorder (HD) with qualitative methods from cultural anthropology, we hope to build a patient-centered approach that will allow us to better understand the clinician perspectives on patient motivations and explanatory models of individuals with HD, and improve treatment outcomes. We describe the ways that these methodologies are productively merged in this project as a result of TL1 collaboration, and present a preliminary picture of methodological and theoretical issues uncovered as part of this processes. We further describe the analytical methods used for this project, and explore issues raised through the combination of psychological and anthropological data and insights. METHODS/STUDY POPULATION: This study represents an attempt to combine the qualitative methodologies of cultural anthropology with the clinical knowledge of psychology and psychiatry in order to better understand gaps between provider and patient beliefs and knowledge about hoarding disorder. This study will present preliminary methodological issues arising from interviews with hoarding experts. RESULTS/ANTICIPATED RESULTS: This study will discuss preliminary issues including shared language, strengths and limitations of both disciplines, and factors for consideration when combining these disparate methodologies. It will close with recommendations for consideration when moving forward with similar collaborations. DISCUSSION/SIGNIFICANCE OF IMPACT: This project seeks to unite psychological and social factors that may contribute to the lived experience of individuals with HD in order to better understand the way that HD is manifested. It also unites disparate methodologies to provide us with a more holistic and complete picture of the experience of HD. While HD has been studied within psychiatry, it has never been assessed using the qualitative methods of anthropology. These methods provide the possibility of expanding knowledge about the ways that this disorder is experienced by individuals and their families, and potentially impacted by shared beliefs and cultures. Furthermore, qualitative data of this nature provides a patient perspective on the experience of HD as a psychiatric illness. This patient perspective can be used to better inform treatment, improve patient outcomes, and to allow providers and researchers to gain a fuller understanding of this complex population.
3184 Development of a Leadership Assessment Scale in Translational Science
Authors: Vaughan Roger , Kost Rhonda G , Brassil Donna , Romanick Michelle , Coller Barry S.
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to help concretize the relevant constructs, and then usied these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively creating domain-specific survey items, and then further discussed and refining the number, grouping, and wording of the items. METHODS/STUDY POPULATION: We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars. Each item was answered using a six-point Likert scale where a low score indicated poor expression of the specific leadership attribute and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Means, medians, standard deviations, and ranges of each item were calculated and tabulated. A complete (Pearson) correlation matrix was computed so that the raw inter-item relationships can be observed. For each a priori Domain an equal weighted summary scale was created and tabulated for review. The internal consistency of each a priori scale was assessed by calculating Cronbach’s Alpha (α). Items with low Item to Construct coefficients were candidates for elimination or modification, and overall scales with low’s will undergo further discussion. To challenge our assumptions of the construction and integrity of each domain, we employed exploratory Principal Components Analysis (PCA), followed by orthogonally rotated Factor Analysis (FA). We also forced the PCA / FA analysis to extract the a priori dimensions that allowed us to compare if the empirical and a priori structures match. DISCUSSION/SIGNIFICANCE OF IMPACT: We are partnering with the CTSA programs at Penn and Yale to assess issues of generalizability and scalability. We are working with Vanderbilt to install survey onto REDCap for ease of dissemination. Will continue to assess psychometric properties and refine as we receive more input.
3072 Scientometric Analysis of the Puerto Rico Clinical and Translational Research Consortium (PRCTRC) Research Publications, 2010-2017
Authors: Cintrón Mariela Torres- , Noboa Carlamarie , Lugo-Pico Mariela , Gonzalez-Sepulveda Lorena , Perez Naydi , Serbia Zulmarie De Pedro- , Irizarry-Ramírez Margarita
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to evaluate the impact of the research and the scientific collaborations as shown in research publication supported by the PRCTRC. METHODS/STUDY POPULATION: Manuscripts published from 2010 to 2017 were retrieved from the Science Citation Index database. Our search criteria included manuscripts: 1) with the PRCTRC grant number and 2) with a PMCID number. Scientometric indicators including h-index (HI), average citation (AC), collaboration coefficient (CC), collaboration index (CI) and degree of collaboration (DC) were calculated using the Web of Science Platform and Stata software for statistical inquiry. Joinpoint was used to calculate the annual percent change (APC). RESULTS/ANTICIPATED RESULTS: A total of 316 publications were identified from 2010-2017, with an average of 39.5 publications per year, and a total of 2,383 citing articles without self-citations. During this period a significant growth (APC = ¬15.3%, p < 0.05) of scientific production was observed. The overall HI was 28, and the AC per item was 9.31. Regarding collaboration, the overall CC was 0.82, the CI was 6.93, and the DC was 99.3. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrated that the PRCTRC scientific production increased statistically significantly. Application of the scientometric indicators allows the PRCTRC assess the research productivity and collaboration to design and implement interventions according to program experience and needs.
3206 Associations between prenatal maternal stress due to a natural disaster and effortful control in early childhood
Authors: Rodriguez-Soto Nayra del Carmen , Martinez Karen G
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: For this reason, our overall objectives are to determine (i) whether natural disaster-related PNMS alters infants’ EC at two years of age, and (ii) if the timing of exposure moderates its effects on toddlers EC. METHODS/STUDY POPULATION: We propose a longitudinal study with 50 mother-toddler dyads. Natural disaster-related PNMS would be measured at 12-18 and 24-30 months of age and will include: objective exposure and maternal distress. EC will be measured with a questionnaire and a Laboratory Temperament Assessment Battery at two years of age. To accomplish our objectives, we will conduct regression and moderation analyses. RESULTS/ANTICIPATED RESULTS: We anticipate that children exposed to Hurricane-related PNMS would present low EC levels compared to those with low prenatal exposure. DISCUSSION/SIGNIFICANCE OF IMPACT: These results are expected to provide evidence for further promoting early intervention and ameliorating adverse effects of PNMS on child outcomes.
3270 Patient Attitudes Survey to Guide Development of a Cell Replacement Device for the Management of Type 1 Diabetes
Authors: Law Ethan William
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: This study aims to estimate patient attitudes and receptiveness towards stem cell-based cell replacement devices to management Type 1 Diabetes. The primary outcomes of this study are mean response values to questions interrogating patient attitudes, knowledge, and receptiveness. METHODS/STUDY POPULATION: A RedCap survey was generated for this study. 100 participants will be drawn from Mayo Clinic Rochester, MN patients living with Type 1 Diabetes. RESULTS/ANTICIPATED RESULTS: Response values will be used to estimate broader patient attitudes. DISCUSSION/SIGNIFICANCE OF IMPACT: The response values of this survey will help inform future directions of cell replacement device development. Additionally, understanding patient attitudes may be useful in crafting more effective education strategies.
3367 A Mouse Model of APOE Genotype in Chemotherapy Related Cognitive Impairment
Authors: Demby Tamar , William Rebeck G. , Albanese Christopher , Rodriguez Olga C. , Lee Yichien , Mandelblatt Jeanne
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Chemotherapy-related cognitive impairment (CRCI) affects 15-35% of breast cancer survivors and constitutes a significant challenge for survivor quality of life. Among older breast cancer survivors who received chemotherapy treatment, carriers of at least one ɛ4 allele of the APOE gene, which encodes apolipoprotein E, are at higher risk for developing CRCI than non-carriers. APOE4 is well characterized as the strongest genetic risk factor for Alzheimer’s disease, but how it contributes to CRCI is not yet understood, and no animal models of APOE genotype and CRCI have yet been established. To better understand how APOE4 acts as a risk factor for CRCI, we used APOE targeted replacement (TR) mice to develop a model of its effects on cognition following treatment with doxorubicin, a chemotherapy drug commonly used in breast cancer treatment. METHODS/STUDY POPULATION: Twelve-to-thirteen month old APOE3 and APOE4 targeted replacement mice expressing human APOE3 or human APOE4 under control of the endogenous murine promoter were treated with 10 mg/kg doxorubicin or equivolume saline given via two IP injections spaced one week apart. One week post-treatment, mice were tested using Open Field and Elevated Zero apparatuses to assess baseline locomotive activity and anxiety and exploratory behaviors. Five weeks post-treatment, mice were assessed using the Barnes Maze over four days of training trials and one 72 hour memory probe. RESULTS/ANTICIPATED RESULTS: We found no differences in Open Field and Elevated Zero behavior, indicating limited influence of doxorubicin treatment on locomotive and anxiety behaviors in both genotypes. During Barnes Maze training, APOE4 mice treated with doxorubicin showed increased latency compared to untreated APOE4 mice as well as treated and untreated APOE3 mice, indicating deficiencies in spatial learning. In APOE3 mice, no differences in performance were seen between doxorubicin-treated and untreated mice (n = 15-16/group, p <.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate that APOE4 targeted replacement mice have specific cognitive vulnerabilities to doxorubicin treatment that can be reliably detected using the Barnes Maze assessment. Future directions include experiments to determine how other chemotherapy drugs or drug combinations impact cognition of APOE4 mice. Ultimately this model may be used to assess preventive measures or therapies for CRCI in the vulnerable APOE4 carrier population with the ability to validate cognitive impacts of these interventions.
3174 Tumor suppressors p53 and ARF control oncogenic potential of triple-negative breast cancer cells by regulating RNA editing enzyme ADAR1
Authors: Kung Che-Pei , Bross Emily , Bramel Emily , Freeman Eric , Sabloak Thwisha , Kuzmicki Catherine , Benjamin Mike , Maggi Leonard , Weber Jason
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Triple-negative breast cancer (TNBC) accounts for one-fifth of the breast cancer patient population. The heterogeneous nature of TNBC and lack of options for targeted therapy make its treatment a constant challenge. The co-deficiency of tumor suppressors p53 and ARF is a significant genetic signature enriched in TNBC, but it is not yet clear how TNBC is regulated by this genetic alteration. METHODS/STUDY POPULATION: To answer this question, we established p53/ARF-defective murine embryonic fibroblast (MEF) to study the molecular and phenotypic consequences in vitro. Moreover, transgenic mice were generated to investigate the effect of p53/ARF deficiency on mammary tumor development in vivo. RESULTS/ANTICIPATED RESULTS: Increased transformation capability was observed in p53/ARF-defective cells, and formation of aggressive mammary tumors was also seen in p53-/-ARF-/- mice. RNA-editing enzyme ADAR1 was identified as a potential mediator for the elevated oncogenic potential. Interestingly, we found that the overexpression of ADAR1 is also prevalent in human TNBC cell lines and patient specimen. Using short hairpin RNA (shRNA) to reduce ADAR1 expression abrogated the oncogenic potential of human TNBC cell lines, while non-TNBC cells are less susceptible. Different levels of RNA editing of known ADAR1 targets were detected in shRNA-treated human TNBC cell lines, suggesting that ADAR1-mediated RNA editing contributes to TNBC pathogenesis. DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate critical roles played by the tumor suppressors p53 and ARF in the pathogenesis of TNBC, partially through affecting ADAR1-mediated RNA editing. Further understanding of this pathway could shed light on potential vulnerabilities of TNBC and inform the development of personalized therapies based on patients’ genetic signiatures.
3510 Academic influence in gynecologic oncology is associated with industry funding: an analysis of the Open Payments database
Authors: Samuel David , Adler Shelby , Vilardo Nicole , Gressel Gregory
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Industry payments to physicians can present a conflict of interest. The Physician Payments Sunshine Act mandates the disclosure of these financial relationships to increase transparency. Recent studies in other surgical specialties have shown that research productivity is associated with greater industry funding. In this study, we characterize the relationship between academic influence and industry funding among academic gynecologic oncologists. METHODS/STUDY POPULATION: Departmental websites were used to identify academic gynecologist oncologists and their demographic information. The Hirsch index (h-index) relates an author’s number of publications to number of times referenced by other publications, a validated measure of an author’s academic influence. This was obtained from the Scopus database. The Center for Medicaid and Medicare Services Open Payments online database was searched for all industry payments in 2017. The NIH Reporter online database was searched for active grants. Goodness of fit testing showed that all variables followed nonparametric distributions. Medians were compared using Mann-Whitney U tests and Kruskal-Wallis analysis of variance with post-hoc Dunn’s test. RESULTS/ANTICIPATED RESULTS: Four hundred and sixty-six academic gynecologic oncologists were included in the analysis. In 2017, 89.7% of this group received industry funding totaling $41.4 million. Median industry funding was $453 [IQR $67-19684] and median h-index was 14 [IQR 8-26]. Only 8.1% of gynecologic oncologists were NIH grant recipients and they received significantly higher industry payments ($357 vs. 11,168, P<0.01). Gender and academic rank were not associated with industry funding. Gynecologic oncologists in the highest decile of industry funding received a median payment of $447,651[N=46, IQR $285,770 – 896,310] totaling $36.5 million. The median h-index for this top-earning decile was 23 [N=46, IQR 16.5-30.3]. When stratified by payment amount, median h index increased but only reached statistical significance in the highest cohort receiving >$100,000 (N = 63, P<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: The majority of academic gynecologic oncologists receive industry funding although there are large variations in payments. Those receiving the largest payments are more likely to hold NIH grants and have greater academic influence.
3577 Adiposity and Fibroblast Growth Factor 23 in nondiabetic patients with moderate-to-severe Chronic Kidney Disease
Authors: Akwo Elvis , Robinson-Cohen Cassiane , Alsouqi Aseel , Siew Edward , Ikilzer Alp , Hung Adriana
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The main aim of this study was to investigate the relationship between measures of adiposity and FGF-23 in a sample of patients with CKD stages 3-4. METHODS/STUDY POPULATION: This study was a clinic-based cross-sectional investigation of 71 CKD patients who underwent body composition and anthropometric assessments as part of the relationship of insulin sensitivity in kidney disease and vascular health (RISKD) study. Dual energy x-ray absorptiometry (DEXA) scans were used to measure total fat mass and body mass index (BMI) was computed using baseline weight and height measurements. Biomarkers included serum FGF-23 (C-terminal), serum leptin, high sensitivity C-reactive protein (hsCRP), serum triglycerides, high density lipoprotein (HDL) cholesterol and total cholesterol. Creatinine-based estimated glomerular filtration rate (eGFR) was computed using the CKD-EPI equation. Multiple linear regression with robust standard errors was used to investigate the relationship between FGF2-3 and measures of adiposity (BMI, total fat mass and serum leptin). Log-transformation was performed for variables (FGF-23, hsCRP and serum lipids) with considerable skewness. RESULTS/ANTICIPATED RESULTS: The median age of the study participants was 68 (IQR: 60, 73) years; 26% were female and 23% were African-American. Median eGFR was 46.9 ml/min/1.73m2 (IQR: 41.9, 52.8), median BMI was 31 kg/m2 (IQR: 27, 35). Log FGF-23 had a significant positive correlation with BMI (r = 0.27, p = 0.02), total fat mass (r = 0.30, p = 0.01) and serum leptin (r = 0.43, p < 0.0001). After full adjustment for age, sex, race, eGFR, log hsCRP, log HDL and log triglycerides, a 50% increase in FGF-23 was associated with a 1 kg/m2 [95% CI: 0.1, 1.9; p = 0.03] increase in BMI, a 2.5 kg [95% CI: 0.2, 4.8; p = 0.03] increase in total fat mass and a 6.7 ng/mL [95% CI: 1.0, 12.4; p = 0.02] increase in serum leptin. DISCUSSION/SIGNIFICANCE OF IMPACT: In this sample of patients with moderate-to-severe CKD, we found a significant independent association between higher FGF-23 levels and higher adiposity (BMI, total fat mass and the pro-atherogenic adipocytokine, leptin). The underlying causes and the implications of these associations − particularly in bone and vascular health − need to be further investigated.
3145 An Evaluation of Machine Learning and Traditional Statistical Methods for Discovery in Large-Scale Translational Data
Authors: Hollister Megan C , Blume Jeffrey D.
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: To examine and compare the claims in Bzdok, Altman, and Brzywinski under a broader set of conditions by using unbiased methods of comparison. To explore how to accurately use various machine learning and traditional statistical methods in large-scale translational research by estimating their accuracy statistics. Then we will identify the methods with the best performance characteristics. METHODS/STUDY POPULATION: We conducted a simulation study with a microarray of gene expression data. We maintained the original structure proposed by Bzdok, Altman, and Brzywinski. The structure for gene expression data includes a total of 40 genes from 20 people, in which 10 people are phenotype positive and 10 are phenotype negative. In order to find a statistical difference 25% of the genes were set to be dysregulated across phenotype. This dysregulation forced the positive and negative phenotypes to have different mean population expressions. Additional variance was included to simulate genetic variation across the population. We also allowed for within person correlation across genes, which was not done in the original simulations. The following methods were used to determine the number of dysregulated genes in simulated data set: unadjusted p-values, Benjamini-Hochberg adjusted p-values, Bonferroni adjusted p-values, random forest importance levels, neural net prediction weights, and second-generation p-values. RESULTS/ANTICIPATED RESULTS: Results vary depending on whether a pre-specified significance level is used or the top 10 ranked values are taken. When all methods are given the same prior information of 10 dysregulated genes, the Benjamini-Hochberg adjusted p-values and the second-generation p-values generally outperform all other methods. We were not able to reproduce or validate the finding that random forest importance levels via a machine learning algorithm outperform classical methods. Almost uniformly, the machine learning methods did not yield improved accuracy statistics and they depend heavily on the a priori chosen number of dysregulated genes. DISCUSSION/SIGNIFICANCE OF IMPACT: In this context, machine learning methods do not outperform standard methods. Because of this and their additional complexity, machine learning approaches would not be preferable. Of all the approaches the second-generation p-value appears to offer significant benefit for the cost of a priori defining a region of trivially null effect sizes. The choice of an analysis method for large-scale translational data is critical to the success of any statistical investigation, and our simulations clearly highlight the various tradeoffs among the available methods.
3002 Effect of Long-Term NSAID Use on Opioid Abuse and Health Outcomes among Breast Cancer Patients
Authors: Onyeakusi Nnaemeka E , Gbadamosi Semiu , Mukhtar Fahad , Orji Chinelo , Ugwuowo Ugochukwu , Igbeta Onyenikewe , Adejumo Adeyinka
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Cancer related pain presents a significant risk for opioid abuse among cancer survivors and contributes to the current opioid crisis. Nearly 90% of breast cancer patients have been reported to have cancer-related pain requiring treatment. Opioids, in combination with NSAIDs, have been widely used for pain management in this population despite the risk of abuse. Long-term NSAID use due to their antineoplastic and neuroprotective effects may offer additional protective effects against opioid abuse. Here, we assess the relationship between NSAID use and opioid abuse among breast cancer patients. METHODS/STUDY POPULATION: Using ICD-9-CM codes, we identified and selected women aged >18 years with breast cancer from the National Inpatient Sample (NIS). Our primary predictor was a history of long-term NSAID use. Opioid abuse was the primary outcome of interest. Secondary outcomes were inpatient mortality and length of stay. Multivariable regression models were employed in assessing the association between predictors and outcomes while adjusting for relevant covariates. RESULTS/ANTICIPATED RESULTS: Among 170,644 women with breast cancer, 7,838 (4.6%) reported a history of long-term NSAID use. Patients with a history of long-term NSAID use had lower odds of opioid abuse (aOR 0.53; 95% CI [0.32-0.88]) and in-hospital mortality (aOR 0.52; 95% CI [0.45-0.60]) and were likely to have shorter hospital stay (7.12 vs. 8.11 days) compared to women with no history of long-term NSAID use. DISCUSSION/SIGNIFICANCE OF IMPACT: Long-term NSAID use may offer a protective effect against opioid abuse and improve in-hospital outcomes translating to better quality of life and healthcare utilization indices among breast cancer patients.
A SELF-REFLEXIVE PRAXIS: CHANGING ATTITUDES TOWARDS MANUSCRIPT AND TEXT IN EARLY CHINA
Authors: Krijgsman Rens
Published: March 2019

This article examines the attitudes of Warring States textual witnesses to the increase in presence of and reliance on bamboo manuscripts in communicating knowledge. Based on a rereading of transmitted materials and four manuscript texts (*Wuwang JianzuoA and B,*Baoxun, and theZhou Wuwang you ji) from the Warring States period, I analyze how contemporaries dealt with questions about the status of (manuscript) texts, their use and transmission, their trustworthiness, and their ability to preserve knowledge. These are texts that talk about themselves. They remark upon the physicality of text and the act of writing, the problem of oral and written transmission, and the differences in the ability of memory and manuscripts to store, hide, and reveal knowledge. I argue that these different reflections reveal a change in the predominant medium of communicating knowledge towards an increased reliance on bamboo manuscripts gradually and partially replacing traditional knowledge practices.
Reproductive Politics in Twentieth-Century France and Britain
Authors: Olszynko-Gryn Jesse , Rusterholz Caroline
Published: March 2019

This special issue adopts a comparative approach to the politics of reproduction in twentieth-century France and Britain. The articles investigate the flow of information, practices and tools across national boundaries and between groups of experts, activists and laypeople. Empirically grounded in medical, news media and feminist sources, as well as ethnographic fieldwork, they reveal the practical similarities that existed between countries with officially different political regimes as well as local differences within the two countries. Taken as a whole, the special issue shows that the border between France and Britain was more porous than is typically apparent from nationally-focused studies: ideas, people and devices travelled in both directions; communication strategies were always able to evade the rule of law; contraceptive practices were surprisingly similar in both countries; and religion loomed large in debates on both sides of the channel.