bluuebunny/crossref_metadata_2025 huggingface dataset:
3029 Willingness to Engage in a Statewide Virtual Community for Biomedical Research
Authors: Patten Christi , Eder Milton , Brockman Tabetha A , Hendricks Deborah , Soto Miguel Valdez , Rocha Maria Zavala , Amelang Miriam , Wi Chung , Balls-Berry Joyce E.
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Virtual communities are an untested method to enhance community engagement in biomedical research. Our CTSA Hubs collaborated to assess receptivity to engage in a statewide Facebook (FB) group. METHODS/STUDY POPULATION: Cross-sectional online survey administered via iPads at the MN State Fair in 2018 to adults aged 18+ years residing in MN assessed demographics, social media use, interest in participating in a FB group for biomedical research; and open-ended questions on health topics of interest, and what would keep people engaged in this group. RESULTS/ANTICIPATED RESULTS: Respondents (N=487) were 21% racial minorities and 65% female sex. Most (87%, n=422) had created a personal FB profile. Of these, the proportion who agreed/strongly agreed was: 57% that the FB group sounded interesting, 45% were interested in being part of it, 41% were willing to share it with others, 62% that it would allow the community’s thoughts/ideas to be heard and 59% wanted to learn about opportunities to participate in research on health topics they care about. Using content analysis, the top 3 health topics people wanted to learn about were chronic disease and prevention, wellness, and mental health. Top ways to keep people engaged were providing personable, relevant health information; and interactive bi-directional discussions. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings will inform development of a FB group to engage diverse populations in biomedical research.
3379 Associations between Diabetes Mellitus and Sublingual Microvascular Disease: A Prospective Cross-Sectional Study
Authors: Smilowitz Nathaniel R , Windheim Joseph , Simon Elias , Reynolds Harmony
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Diabetes mellitus (DM) is a risk factor for the development of microvascular complications. We sought to determine the association between diabetes mellitus status and microvascular circulatory disease, as measured in the sublingual capillary bed. METHODS/STUDY POPULATION: We prospectively recruited adults with cardiovascular (CV) risk factors or established CV disease, with and without DM, who were referred for invasive coronary angiography at an urban tertiary care medical center. All participants underwent non-invasive sublingual sidestream darkfield microscopy. The primary outcome was the perfused boundary region (PBR), a measure reflecting the extent to which red blood cells (RBC) penetrate the sublingual glycocalyx in vessels between 5 and 25 µm in width. RESULTS/ANTICIPATED RESULTS: 57 participants were enrolled. The mean age was 66.1 ± 11.1 years and a majority of participants (66%) were men. DM was present in 18 (31.6%) participants. Sublingual PBR measurements were not different between participants with and without DM overall (1.93µm vs. 1.96µm, p=0.63) or in vessels with high flow (1.48µm vs. 1.59µm, p=0.08). No differences in capillary RBC filling (72.9% vs 73.0%, p=0.95) or perfused microvascular density (3112 vs. 3236 µm/mm2, p=0.32) by DM status were observed. DISCUSSION/SIGNIFICANCE OF IMPACT: In a population of adults with CV risk factors or disease, DM was not associated with impaired sublingual microvascular glycocalyx. Additional investigation into diabetes-induced microvascular impairment is warranted.
3296 Endometrial cancer microbiome biomarker for disease detection and microbial role in the disease
Authors: Walther-Antonio Marina , Walsh Dana , Liu Yuguang , Yao Janet , Chia Nicholas , Nelson Heidi , Mariani Andrea
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Our primary objective is to determine whether the bacteria exerts its effect intra- or extra-cellularly. We have genomic and microscopy preliminary evidence indicating that the bacteria is capable of invading endometrial cells. Our secondary objective is to identify what type of impact the bacteria have on the host cells and whether they are capable of transforming the host cells from a benign into a malignant phenotype. We are currently testing a putative mechanism by which the bacteria may cause the overexpression of the hypoxia inducible factor (HIF), a hallmark of endometrial cancer. METHODS/STUDY POPULATION: We are utilizing our custom built optofluidics platform (microfluidics platform incorporated into an advanced microscope with optical laser tweezers) to isolate single cells from the endometrial tissues of 150 patients with and without endometrial cancer. We are utilizing single cell whole genome amplification followed by qPCR to identify if the bacteria is present intracellularly. We are coupling this procedure with standard microbiological invasion assays with endometrial cell line cultures and P.somerae. We are also utilizing our optofluidics platform to perform single cell transcriptomic amplification, followed by sequencing of cells invaded or in the presence of the bacteria to determine the impact in the transcriptome of the host cell. We are coupling this with western blots of factors hypothesized to be impacted by the bacteria in the overexpression of HIF. RESULTS/ANTICIPATED RESULTS: Based on our preliminary data we anticipate to find evidence that P.somerae is invading the host cells, in particular the cells in tumor tissues. We also expect to find that the intracellular presence of the bacteria is causing the overexpression of the HIF pathway, hence resulting in a cancerous phenotype. DISCUSSION/SIGNIFICANCE OF IMPACT: Our long-term goal is to develop primary prevention strategies that will reduce endometrial cancer incidence rates. A confirmation of our hypothesis could suggest that it is sufficient for endometrial cancer prevention efforts to eliminate P.somerae, in line with gastric and cervical cancer efforts. It could also mean that targeting P.somerae in cancer treatment is necessary to contain the disease and prevent recurrence.
3420 Estradiol levels are elevated in older men with diffuse cutaneous SSc and are associated with decreased survival
Authors: Baker Frost DeAnna , Wolf Bethany , Peoples Christine , Fike Jessica , Silver Katherine , Laffoon Maureen , Medsger Thomas A. , Feghali-Bostwick Carol
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Our objective was to examine serum E2 levels in dcSSc males in relation to disease characteristics (i.e autoanitbody profile and internal organ involvement) and its impact on survival. METHODS/STUDY POPULATION: We measured serum E2 levels in 83 dcSSc men >50 years old from the University of Pittsburgh Scleroderma Center and healthy controls of similar age. Using statistical modeling, we examined the associations between circulating E2 levels, internal organ involvement, autoantibody profiles, and survival. RESULTS/ANTICIPATED RESULTS: Male dcSSc patients had significantly higher serum E2 levels compared to healthy male controls and compared to dcSSc post-menopausal women of similar age. Male dcSSc patients with high serum E2 levels had significantly more heart involvement and worse survival. Using Cox regression modeling for risk of death, increasing serum E2 levels in anti-Scl-70 antibody positive dcSSc males were associated an increased risk of death. DISCUSSION/SIGNIFICANCE OF IMPACT: DcSSc male patients have higher levels of E2 compared to healthy controls and dcSSc postmenopausal women. Elevated serum E2 levels in dcSSc males >50 are associated with heart involvement and, if anti-Scl-70 antibody positive, worse survival. Our current study expands on our previous work, not only that that E2 exerts pro-fibrotic effects on skin, but also internal organ involvement, overall survival. These data suggest an important role of estrogen imbalance in SSc.
3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice
Authors: Zuckerman Pamela Cabahug , Liu Chao , Fang Emily , Castillo Alesha B
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Our aim is to test whether osteocyte-specific CXCL12 expression is critical to exercise-driven bone formation. METHODS/STUDY POPULATION: All procedures were approved by the NEW YORK UNIVERSITY Institutional Animal Care and Use Committee. We generated male and female mice in which CXCL12 was deleted from OCYs (CXCL12ΔOCY) by crossing CXCL12 floxed mice and 10kb DMP1-Cre transgenic mice (gifts from Drs. Geoffrey Gurtner and Lynda Bonewald, respectively). The 10kb DMP1-Cre has been shown to be robustly expressed in odontoblasts and OCYs, with little to no activity in cells from non-mineralized tissues (Lu+ J Dent Res 2007). Growing male and female mice (n=3-8/group) were given fluorochrome labels every two weeks between 4-16 weeks of age, to monitor the role of CXCL12 during development. A second group, of adult 16-week-old mice (n=5/group), were subjected to tibial axial cyclic loading (1200µɛ, 2Hz, 120cycles, 3days/wk for 2 wks) (Liu+ Bone 2018). Basal and load-induced periosteal (Ps) and endosteal (Es) mineralizing surface (MS/BS, %), mineral apposition (MAR, µm/day) and bone formation rates (BFR/BS, µm3/µm2/year) were calculated (Dempster+ JBMR.2013) at mid-length. RESULTS/ANTICIPATED RESULTS: No significant differences were detected in basal bone formation during development. However, relative load-induced Ps MAR (rMAR) was reduced by 50% in female (p=0.02) and 75% in male (p=0.002) CXCL12ΔOCY mice; and similarly, Ps rBFR/BS was reduced by 50% in female (p=0.01) and 70% in male (p=0.001) CXCL12ΔOCY mice (Figure 1). Es bone formation was not affected by CXCL12 deletion. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, osteocyte-specific CXCL12 expression plays a critical role in exercise-driven periosteal new bone formation, suggesting that CXCL12 signaling may positively regulate osteogenic differentiation and/or mature osteoblast function. Further underlying mechanisms are currently being explored. Thus, osteocyte-specific CXCL12 signaling may be a promising target to enhance load-induced bone formation in patients with compromised ability to form new bone.
3468 Predictive biomarkers of platinum-based chemotherapy response in Puerto Rican Hispanics with high-grade serous ovarian cancer.
Authors: Reyes-Gonzalez Jeyshka M. , Umpierre Sharee , Vivas-Mejia Pablo E.
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: High-grade serous ovarian carcinoma (HGSOC) is the most common and malignant histological subtype of epithelial ovarian cancer. While the majority of HGSOC patients initially respond to platinum-based chemotherapy, they often present with recurrent chemoresistant disease, which is extremely fatal. Therefore, there is an urgent need to identify predictive biomarkers of platinum response and to develop rational, targeted therapies to improve the outcome of patients with HGSOC. The objectives of the present study are to profile and assess the clinical significance of MYC network dysregulation in HGSOC. METHODS/STUDY POPULATION: We will conduct a retrospective cohort study of Puerto Rican Hispanics with HGSOC who underwent surgery followed by platinum-based chemotherapy at clinical institutions in Puerto Rico. Medical records, pathology reports, and cancer registries will be reviewed to extract data on clinicopathological features, disease recurrence, and death. For eligible patients, formalin-fixed, paraffin-embedded (FFPE) tissue samples will be processed and analyzed by quantitative Real Time PCR (qRT-PCR) and immunohistochemistry (IHC). RESULTS/ANTICIPATED RESULTS: Expression levels of MYC and MYC-related molecules are expected to correlate with clinicopathological features and prognosis of HGSOC. DISCUSSION/SIGNIFICANCE OF IMPACT: The identification and validation of clinically-relevant alterations in HGSOC, such as dysregulation of the MYC network, will be crucial to guide therapy regimen, maximize clinical benefit, and improve patient outcome.
3285 Toxicity of Released B Cell Products in Multiple Sclerosis: Effects on Neurons and Oligodendrocytes
Authors: Zuroff Leah , Touil Hanane , Romer Micah , Nedelkoska Liljana , Benjamins Joyce A. , Lisak Robert P. , Grinspan Judith B. , Bar-Or Amit
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: We previously demonstrated that products released by cultured B cells from patients with Multiple Sclerosis (MS) are cytotoxic to neurons and oligodendrocytes, while minimal toxicity was observed in response to B cell secretory products from age- and sex-matched normal controls. The goal of this proposal is to identify the range of brain cells susceptible to MS B cell-mediated cytotoxicity, to define the cytotoxic factor(s) released by MS B cells, and to determine whether particular subset(s) of MS B cells harbor the greatest pathogenic potential. METHODS/STUDY POPULATION: The toxicity of B cell products will be demonstrated by incubating primary rat cultures of neurons, oligodendrocytes, and oligodendrocyte progenitor cells (OPCs) with B cell supernatants. B cells will be isolated from the peripheral circulation of untreated relapse-remitting MS (RRMS) patients and age- and sex-matched normal controls. The identification of specific toxic factor(s) in MS B cell supernatants will be achieved through a combination of exosome-depletion/enrichment of conditioned media, proteomics, next generation sequencing, and lipidomics. Determining pathogenic B cell subsets will be achieved by cell sorting into memory and naïve B cell subsets prior to collection of supernatants. RESULTS/ANTICIPATED RESULTS: We hypothesize that the toxicity of MS B cell products is mediated, at least in part, by extracellular vesicles, such as exosomes. We expect depletion of these exosomes from the B cell conditioned media or inhibition of their biogenesis will mitigate the observed toxicity. Furthermore, differences in B cell-derived exosomal content, such as proteins, (mi)RNAs, or lipids, likely explain the differences in observed toxicity. Lastly, we hypothesize that memory B cells, which are enriched in the CNS of MS patients and demonstrate a more pro-inflammatory profile than naïve B cells, are responsible for the toxicity observed in supernatants of total B cells. DISCUSSION/SIGNIFICANCE OF IMPACT: MS is the most prevalent chronic inflammatory disease of the CNS, affecting more than 2 million people worldwide. Although over a dozen disease-modifying therapies are approved for the treatment of RRMS, none are meaningfully effective at limiting disease progression. This proposal will provide new insight into immune-CNS interactions in progressive MS and provide much-needed novel targets for therapeutic intervention, either via blocking identified toxic molecule(s) or by selectively depleting pathogenic B cell subsets.
3539 Relationship between dental fluorosis, water and serum levels of fluoride and chronic kidney disease in children: Data from National Health and Nutrition Examination Survey
Authors: Shaheen Magda , Sadeghi Erfun , Teklehaimanot Senait
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The aim of the study is to examine the relation between dental fluorosis, serum and water levels of fluoride and Chronic Kidney Disease (CKD) among children. A link between dental fluorosis, fluoride level and CKD can be an indicator of the blind danger of fluoride toxicity that poses a great threat to the human health. METHODS/STUDY POPULATION: Dental fluorosis, serum and water levels of fluoride and CKD were examined in children 6-19 years old, using data from the National Health and Nutrition Examination Survey1999-2012 and 2013-2016. We used multiple logistic regression to adjust for the confounders (demographics, insurance, dental visit, and co-morbidity) to assess the relation between dental fluorosis, serum and water levels of fluoride and CKD. STATA 14.0 was used to analyze the data (sample design and weight). P < 0.05 is statistically significant. RESULTS/ANTICIPATED RESULTS: The prevalence of CKD was 13.9% and dental fluorosis was 34.3%. In the multivariate model, plasma fluoride level was independently associated with CKD (Adjusted Odds Ratio (AOR) = 1.68, 95% Confidence Interval (CI) = 1.06-2.68, p = 0.029) but not with dental fluorosis (AOR = 1.4, 95% CI = 0.87-2.2, p = 0.17) or water fluoride level (AOR = 0.91, 95% CI = 0.59-1.396, p = 0.659). DISCUSSION/SIGNIFICANCE OF IMPACT: Results indicated that serum fluoride level is independently associated with CKD but dental fluorosis and water fluoride level were not related to CKD. Increase awareness and screening for fluorosis in children are needed for early detection and prevention of organ damage. Prospective studies related to fluorosis and tissue damage are needed.
3030 Symptom profile of chronic rhinosinusitis versus obstructive sleep apnea in a tertiary rhinology clinic
Authors: Yong Ji Keven Seung , Risoli Thomas J. , Kuchibhatla Maragatha , Chan Lyndon , Hachem Ralph Abi , Jang David
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Patients with undiagnosed obstructive sleep apnea (OSA) will often present to an otolaryngologist with symptoms of chronic rhinosinusitis (CRS). Differentiating CRS from OSA may help obviate unnecessary and costly work-up for CRS. This study analyzes symptom profiles of such patients to help identify which require polysomnography. METHODS/STUDY POPULATION: This is a three-year retrospective analysis of adult patients seen in an academic practice with a rhinologic chief complaint. The 22-Item Sinonasal Outcomes Test (SNOT-22) survey, which is a validated patient-reported outcome measure widely adopted for CRS featuring a symptom scale of 1 (least severe) to 5 (most severe), was completed by patients with untreated OSA confirmed on polysomnography without CRS (OSA group) and a control group of CRS patients (CRS group). Results were compared using Chi-square test (categorical) and Wilcoxon rank-sum test (continuous) with Bonferroni correction, and multiple logistic regression. RESULTS/ANTICIPATED RESULTS: 43 patients were included in the OSA group [mean apnea-hypopnea index: 27.9 (SD: 21.2)] and 124 patients were included in the CRS group. The CRS group demonstrated significantly higher scores in nasal (p < 0.001), extra-nasal (p < 0.001) and ear/facial symptom domains (p = 0.001) while the OSA group reported higher psychological (p = 0.028) and sleep symptom domain scores (p = 0.052). As for the cardinal symptoms of CRS, nasal discharge and loss of smell were significantly higher in the CRS group (both p < 0.001), whereas facial pain (p = 0.117) and nasal obstruction (p = 0.198) were not significantly different between the two groups. After adjustment, for every 1-point increase in a patient’s score for ear pain, thick nasal discharge and loss of smell or taste, their odds of having CRS increased by a factor of 3.18 [(95% CI 1.61-6.29), p = 0.001], 1.60 [(95% CI 1.22-2.10], p = 0.001] and 1.36 [(95% CI 1.04-1.78), p = 0.025], respectively, compared to having OSA. OSA patients were more likely to choose a sleep-related symptom as a “most important complaint” (MIC) (p < 0.001). Facial pain and nasal obstruction were the most common MIC in the rhinologic domain for OSA patients, whereas thick nasal discharge and post-nasal discharge were the most common MIC for CRS patients. DISCUSSION/SIGNIFICANCE OF IMPACT: For patients presenting with rhinologic symptoms, the SNOT-22 can help identify those with undiagnosed OSA. OSA should be suspected in patients with sleep and psychological dysfunction as their primary complaints without the significant nasal drainage and anosmia that characterizes CRS.
3022 Barriers to Accessing Follow-up Care and Changes in Medical Needs after Childhood Injury
Authors: Bell Teresa Maria , Vetor Ashley N , Watson Dennis P , Harle Christopher A , Carroll Aaron E
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to prospectively assess caregiver-perceived barriers to accessing post-acute care for their injured child and determine if caregivers report ongoing, unmet health needs for their children after trauma. METHODS/STUDY POPULATION: This was a prospective cohort study that followed 50 participants for 6 months and administered surveys to parents of children who are admitted to a pediatric level 1 trauma center for injury. Surveys were given bi-weekly regarding care children received after hospital discharge. At 3 months, parents were surveyed over the phone on whether they were able to access all needed health services and if there were any perceived barriers to obtaining or providing at-home care. At 6 months, parents were given the Child & Family Follow-up Survey to assess ongoing physical, mental, social, and scholastic needs. Free responses and transcribed interviews were analyzed using thematic content analysis and frequencies are reported for discrete data. RESULTS/ANTICIPATED RESULTS: Out of 50 families recruited, 47 completed follow-up assessments. At 3 months, common themes regarding challenges after hospital discharge included difficulty scheduling specialist care; uncertainty in managing their child’s pain; transitioning home without enough knowledge to meet their child’s medical needs; lack of communication between multiple providers; distress at having providers release children to full activities before caregivers were comfortable. At 6 months, approximately 24% of parents reported children had ongoing cognitive limitations, 29% reported emotional problems, 19% reported physical limitations, 33.3% reported difficulty in school, and 15% reported play/social difficulties. DISCUSSION/SIGNIFICANCE OF IMPACT: Evidence suggests families face significant barriers in accessing follow-up care, despite nearly universal health insurance coverage for children. Further, a large percentage of parents report ongoing health needs, despite the majority of the cohort having only mild or moderate severity injuries. Making follow-up care more patient-centered for families of traumatically injured children may improve compliance with medical regiments and reduce the likelihood of future disability. Examples of this may be coordinating care among multiple specialty providers, so that patients with multiple injuries can schedule multiple follow-up appointments on the same day. Additionally, more caregiver education on administering pain medication, caring for wounds, and safe practices for returning to full activities would be beneficial for families.
3085 Pediatric provider and staff perceptions of HPV vaccine completion compared to other healthcare providers: Effects on perceived need for change
Authors: Shing Jaimie Zhi , Koyama Tatsuki , Hull Pamela
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: According to Diffusion of Innovations Theory, an important predictor of successful implementation of a new intervention within an organization is perceived need for change (i.e. tension for change [TFC]). No research has examined factors influencing TFC in relation to human papillomavirus (HPV) vaccination. Providers who assume their clinic already performs well in HPV vaccination coverage may perceive a lower need for assistance for improvement. We assessed the association between perceived HPV vaccine completion compared to peer clinics and perceived support needed to increase HPV vaccination coverage. METHODS/STUDY POPULATION: All providers (physicians/nurse practitioners/physician assistants) and staff (clinical/non-clinical) from 21 pediatric clinics participating in an HPV vaccine quality improvement (QI) intervention study in Tennessee were invited to complete a baseline survey. Perceived comparative performance (i.e. perceived HPV vaccine completion compared to peer clinics) and TFC (i.e. perceived support needed to increase HPV vaccination coverage) were measured on continuous scales of 0-100. We used logistic regression to estimate odds of perceiving higher TFC (upper tertile, score of 51-100) for every unit increase in perceived comparative performance. Analyses controlled for age of respondent, perceived strength of evidence for HPV vaccine guidelines, and clinic factors, including culture/climate and available resources. RESULTS/ANTICIPATED RESULTS: Of 325 respondents, most were staff (61%), female (87%), and non-Hispanic White (83%). Respondents who perceived higher HPV vaccination coverage compared to peer clinics perceived lower clinic-level TFC (adjusted OR [aOR] = 0.98; 95% CI, 0.97-0.99). When stratifying by job role, this negative association was observed among providers (aOR = 0.95; 95% CI, 0.92-0.98), but not among staff (aOR = 1.00; 95% CI, 0.98-1.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Providers who perceived higher HPV vaccination coverage compared to peer clinics perceived lower need for support to improve vaccination outcomes. Our results suggest that QI efforts targeting pediatric clinics may find it useful to assess providers’ perceptions of their clinic’s performance, which could affect motivation to engage in QI efforts and successfully improve outcomes.
3233 Von Willebrand Factor is Localized in the Extravascular tissue of Patients with Juvenile Scleroderma
Authors: Canizares Natalia Vasquez , Gil Morayma Reyes , Wahezi Dawn M. , Agarwal Beamon , Rubinstein Tamar
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: To further explore the role of vWF in the pathogenesis of scleroderma by identifying its location within the tissue of sample biopsies obtained as part of routine diagnosis with the use of immuno-histochemical staining. METHODS/STUDY POPULATION: We examined 8 skin biopsies from 2 patients with systemic sclerosis (SSc), 2 with localized scleroderma (LS) and 4 with JDM. Double immunofluorescence staining was performed in each tissue with antibodies against vWF and collagens type I and III. DAPI (4′, 6-diamidino-2-phenylindole) was also used for counterstaining of inflammatory cells. Tissue staining patterns were compared between groups. RESULTS/ANTICIPATED RESULTS: Biopsies were obtained from the upper extremity of 7 females and the lower extremity of 1 male. Median age, symptom duration, and serum levels of vWF antigen around the time of biopsy was 8 years (IQR 4.5-11), 5.5 months (IQR 2.5-7), and 245% (IQR 203-302 for 7 patients), respectively. All but 1 biopsy was performed prior to initiation of immunosuppressive therapy. Immunofluorescence staining showed a superficial and deep perivascular inflammatory cell infiltrate that co-localized with vWF in all tissues. There was expression of vWF in the extravascular tissue of patients with JScl co-localizing with collagen III in the reticular dermis (Figures 1 and 2). In comparison, vWF expression was restricted to the endothelium and did not co-localize with collagen in the dermis of patients with JDM (Figure 3). Patients with SSc had higher expression of vWF as compared to patients with LS. DISCUSSION/SIGNIFICANCE OF IMPACT: vWF may participate in the pathogenesis of cutaneous inflammatory conditions. We have demonstrated that vWF co-localizes with cellular inflammatory infiltrates in the perivascular areas and in the dermis of patients with JScl and JDM. We additionally speculate that vWF may participate in the pathogenesis of fibrosing skin diseases based on evidence of increased extravascular expression in the tissue of patients with JScl (vs. JDM), and its co-localization with collagen. vWF expression intensity in the dermis of JScl patients may relate to disease extension (SSc vs. LS).
3094 Production of Engineered Cardiac Tissue for Disease Modeling
Authors: Ellis Morgan , Lipke Elizabeth
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Cardiovascular diseases (CVD) is the leading cause of death worldwide in both men and women due to lack of cardiac regeneration after disease or damaged is caused. There are many challenges to studying CVD since native cardiomyocytes cannot be cultured in vitro. With the advancements in biomaterial and pluripotent stem cells research, scientists are now able to produce engineered cardiac tissue models in vitro that mimic the native myocardium. This study shows our methods for producing engineered cardiac tissue with potential applications in cardiac regeneration, disease modeling, and scalable production. METHODS/STUDY POPULATION: In this study, human induced pluripotent stem cells (hiPSCs) were combined with two different photocrosslinkable hybrid biomaterials, poly (ethylene)- glycol fibrinogen (PF) and gelatin methacrylate (GelMa), in various tissue geometries to form 3D human engineered cardiac tissues (3D-hECTs). To study tissue growth and contraction, image and video analysis was performed at specific timepoints. To analyze differentiation efficiency and cell population, flow cytometry was performed using cardiac markers. To evaluate gene expression, qPCR was performed using pluripotency and cardiac specific primers. RESULTS/ANTICIPATED RESULTS: Direct cardiac differentiation of encapsulated hiPSCs resulted in synchronously contracting 3D-hECTs in both biomaterials and all tissue geometries. Spontaneous contractions started on Day 7 and increased in velocity, frequency, and synchronicity over time. 3D-hECTs had high cell viability with > 70% of cells positive for cardiac markers. Engineered tissues showed appropriate temporal changes in gene expression over time with pluripotency gene expression decreasing and cardiac gene expression increasing. DISCUSSION/SIGNIFICANCE OF IMPACT: This study shows the potential for direct differentiation of encapsulated hiPSCs to produce physiologically relevant engineered cardiac tissues. Resulting 3D-hECTS showed features of mature myocardium with appropriate cardiomyocyte populations, mechanical motion, and gene expression. Using this platform, we are able to produce engineered cardiac tissue in a variety of biomaterials and tissue geometries to study new therapeutics, mechanism of disease, and scalable tissue culture.
3326 Radiofrequency Renal Denervation Prevents Further Progression of Hypertension and Decreases Renal Medullary Fibrosis in One-year-old Spontaneously Hypertensive Rats (SHR)
Authors: Gao Juan , Denys Ian B , Sutphen Jane , Valle Luis Del , Kapusta Daniel R
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: We have reported that radiofrequency renal denervation (RF-RDN) in SHR at 20-weeks of age, decreased blood pressure (BP) and fibrosis in kidney cortex and medulla when rats were sacrificed at 6 months. However, whether RF-RDN can have similar benefits in older rats remains unknown. This study examined whether performing RF-RDN in older rats also has a beneficial effect on BP and renal fibrosis. METHODS/STUDY POPULATION: Baseline systolic and diastolic BP (SBP/DPB) was measured (telemetry) in nine-month-old SHR and Wistar Kyoto rats (WKY). Groups of rats then received bilateral RF-RDN or Sham-RDN (SHR-RDN, n=9; SHR-Sham, n=10; WKY-RDN, n=5; WKY-Sham, n=8). Rats were then sacrificed at 12-months of age. Kidneys were harvested, sectioned, and assessed for fibrosis by Masson’s trichrome stain. A pathologist, who was blinded to treatment groups, evaluated each kidney section for fibrosis. RESULTS/ANTICIPATED RESULTS: Compared to SHR with Sham-RDN, RF-RDN prevented a further increase in systolic and diastolic BP from baseline (9-month) in SHR as they aged to 12-months (SHR-Sham mmHg: 9-month 193±4/127±4; 12-month 207±3/142±5; SHR-RDN mmHg: 9-month 197±3/132±2; 12-month 197±4/132±3). RF-RDN did not alter SBP or DBP in aged WKY. One-year-old SHR with prior Sham-RDN showed extensive renal fibrosis in kidney cortex and medulla. In contrast, RF-RDN significantly decreased renal fibrosis in the medulla, but not cortex. There was no fibrosis in kidneys of age matched WKY. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that RF-RDN may be a potential therapy for halting progression of hypertension and decreasing medullary fibrosis in the aged population.
3293 Region Specific Dysregulation of Dopaminergic Signaling in Mice Displaying Excessive Over-Grooming
Authors: Foster Daniel , Yohn Samantha , Mahmood Muhammad , Lavery Madigan , O’Brien Daniel , Peng Weimin , Jeffrey Conn P.
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to determine if dopamine signaling is altered in a mouse model displaying excessive self-grooming and further elucidate the potential utility of compounds targeting the striatal DA system in modulating repetitive behaviors. METHODS/STUDY POPULATION: Here, we report studies using fast-scan cyclic voltammetry (FSCV) in mice lacking the postsynaptic protein SAP90/PSD95-associated protein (SAPAP3 KO mice) as well as control littermates. Rodent self-grooming provides a behavioral output with which one can monitor repetitive, self-directed, patterned behavior that has great translational value to OCD-like disorders. Total time spent grooming was monitored in SAPAP3KO mice and control littermates. To further examine the role of DA in regulating repetitive grooming behaviors the magnitude and kinetics of DA transients were assessed using FSCV in ex vivo slice preparations as well as in anesthetized mice in vivo. DA transients were elicited in the dorsolateral striatum (DLS), dorsomedial striatum (DMS); and nucelus accumbens core (NAcc). In some experiments mice were crossed with DAT-Cre animals and channelrhodopsin 2 (ChR2) was virally expressed in DA neurons to allow optical stimulation of DA transients. RESULTS/ANTICIPATED RESULTS: As previously reported, SAPAP3 KO mice showed excessive grooming compared to control littermates at the age assessed (4-5 months). DA transients evoked by a single electrical pulse in slices from SAPAP3 KO mice were not significantly different from those observed in slices from control littermates in any of the regions tested including the DLS, DMS and NAcc. However, when four electrical pulses were applied at a frequency of 10Hz to mimic DA neuron bursting, the magnitude of DA transients observed in the DMS and NAcc of SAPAP3 mice were greater than those evoked in control littermates.Interestingly, phasic stimulation produced similar DA transients in the DLS of both genotypes suggesting that phasic DA signaling was not globally altered. To confirm this finding we crossed SAPAP3 KO mice with DAT-Cre mice and injected ChR2 containing virus into the midbrain to selectively express ChR2 in DA neurons. Transients were then optically evoked resulting in selective activation of DA neurons. Optical stimulation produced a pronounced enhancement of DA release in SAPAP3 KO mice specifically in the DMS and only following phasic-like stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: These exciting findings suggest that DA signaling in SAPAP3KO mice is dysregulated in a very precise manner that is sub-region specific as well as dependent on the pattern of stimulation. These results suggest that targeted therapies that can modulate these specific modes of dopaminergic signaling in these distinct striatal subregions could provide improved efficacy in OCD patients that are resistant to SSRI treatment.
3483 Glycemic Control and Diabetic Peripheral Neuropathy Among Patients on Prescription Opioid Pain Medications in Western New York: Using Data Analytics for Quality Assessment
Authors: Sinha Shyamashree , Lee Robert , Hu Jinwei , Mullin Sarah , Elkin Peter
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: I would like to make clinicians aware about prescription opioid use and glycemic control among patients with diabetes. This is a quality of care issue that increases the disease burden for two conditions opioid dependence and diabetic complications. Big data analytics can bring out this quality of care issue and help in changing clinical practice through precision medicine METHODS/STUDY POPULATION: This is a population health study of patients on prescription opioid pain medications in Erie county medical center and local out patient clinic. The electronic data from the hospital records and Outpatient were collected, merged and de identified. The database was saved in a protected environment and made accessible to researchers through a secure login. The data was queried for the number of patients with diabetes. The glycohemoglobin levels were collected and then the analysis was made RESULTS/ANTICIPATED RESULTS: It was found that only 63 of the 89 patients with DPN and 156 of the 570 patients without DPN had any measurement of HbA1c in our data. It was found that 86 out of 156 patients without DPN had suboptimal glycemic control with a glycohemoglobin level > 7% while 36 out of 63 patients with DPN had a glycohemoglobin > 6.7%. The odds of patients with DPN having poor glycemic control is 0.57 while the odds of having poor glycemic control without DPN is.55. The relative risk being 1.03. DISCUSSION/SIGNIFICANCE OF IMPACT: Our population study revealed suboptimal glycemic control among a large set of patients in Western New York with a diagnosis of diabetes mellitus and a concurrent prescription for an opioid pain medication. A significant percentage of patients in our study population with a diagnosis of DPN might benefit in terms of decreased painful symptoms of neuropathy from monitoring and attempting to improve glycemic control. Additionally, in our patient population, there were no patients with diabetic peripheral neuropathy prescribed pregabalin or duloxetine, the first-line FDA-approved medications for painful DPN, Based on our population study, the quality of care for diabetic patients with DPN who are prescribed opioid pain medications should be monitored closely. First-line, FDA approved anticonvulsants and antidepressants should be considered for the treatment of painful symptoms when necessary. Attention should be directed towards monitoring and improving glycemic control in patients without DPN receiving opioid pain medications to attempt to prevent or delay the microvascular complications of diabetes, including the onset of painful peripheral neuropathy.
3159 Bone Turnover Biomarkers May Discriminate Low Bone Mineral Density in HIV-Infected Adults
Authors: Collins Lauren Frances , Sheth Anandi , Moran Caitlin , Ward Laura , Titanji Kehmia , Easley Kirk , Lennox Jeffrey , Neale Weitzmann M. , Ofotokun Igho
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Persons living with HIV (PLWH) are at increased risk for fragility bone disease. Current osteoporosis screening guidelines do not account for HIV status, and clinical risk assessment tools are not sensitive in PLWH. We examined the value of traditional osteoporosis risk factors, HIV-specific indices, and bone turnover biomarkers in predicting low bone mineral density (BMD) in PLWH. METHODS/STUDY POPULATION: Demographic and clinical characteristics, dual energy x-ray absorptiometry (DXA)-derived BMD, HIV indices (viral load, CD4 count, antiretroviral therapy [ART]), and biomarkers of bone turnover (C-terminal telopeptide of collagen [CTx], osteocalcin [OCN]) were evaluated in a cross-sectional analysis of PLWH (n=248) and HIV- controls (n=183). The primary outcome was low BMD, defined as osteopenia or osteoporosis by WHO criteria. Multivariable logistic and modified Poisson regression models were used to assess associations between low BMD and covariates of interest. RESULTS/ANTICIPATED RESULTS: Overall, median age was 44 years, 48% were male, 88% were black, median body mass index (BMI) was 28 kg/m2, 72% smoked cigarettes, and 53% used alcohol; characteristics did not differ by HIV status. PLWH had a mean CD4 of 408 cells/mm3, 55% were ART-naïve, and 45% had viral suppression on ART. Overall, 25% (109/431) had low BMD, including 31% of PLWH compared to 16% of HIV- controls. In multivariable models, HIV was significantly associated with low BMD (aOR 2.46, 95%CI 1.39-4.34; aRR 1.90, 95%CI 1.18-3.07). Adjusting for HIV, three traditional risks– age, race, and BMI– were independently associated with low BMD in the full cohort. However, bone turnover markers, CTx and OCN, were better able to discriminate low vs. normal BMD in PLWH compared to HIV- controls. In PLWH, mean serum CTx was 23% higher in low vs. normal BMD (mean CTx difference=0.06 ug/mL); in HIV- controls, no association with BMD was observed (mean CTx difference=0 ug/mL). In PLWH, mean serum OCN was 38% higher in those with low vs. normal BMD (mean OCN difference=2.48 ug/mL); in HIV- controls, mean serum OCN was only 16% higher in those with low vs. normal BMD (mean OCN difference=1.08 ug/mL). DISCUSSION/SIGNIFICANCE OF IMPACT: In PLWH as opposed to HIV- controls, serum biomarkers reflecting a high bone turnover state, may discriminate individuals with low versus normal BMD. Because changes in biomarkers precede changes in BMD, these markers should be explored further either alone or in combination with traditional risk assessment tools to improve early screening for osteoporosis in PLWH.
3445 Cannabis use and risk of H. pylori infection; analysis of inpatients and residents of the US.
Authors: Adejumo Adeyinka Charles , Bukong Terence Ndonyi
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Cannabinoids suppress gastric acid secretion, ameliorate gastric inflammation, and promote gastric ulcer healing, all of which are triggered by H pylori (Hp). Our aim was to determine the relationship between cannabis use and: 1) H pylori infection (HPI) among community residents 2) clinical peptic ulcer disease (PUD) and its complications among hospitalized patients. METHODS/STUDY POPULATION: We performed case-control studies with records from the NHANES III (n=4,556) and HCUP-NIS 2014 (n=4,555,029), and respectively identified subjects with seropositivity for H pylori and clinical PUD, and their cannabis usage status. In the NHANES III, we estimated the adjusted prevalence rate ratio (aPRR) of having HPI with cannabis use, using generalized estimating equations. In the NIS, we propensity-matched cannabis users to non-users in ratio 1:1 (68,073:68,073) and measured the aPRR of having PUD and its complications (SAS 9.4). RESULTS/ANTICIPATED RESULTS: In NHANES III, associated with decreased HPI seropositivity were cannabis ever-users (aPRR: 0.79[0.66-0.95]), greater than 10 times lifetime usage (0.65[0.5-0.84]) and recent 31-day usage (0.67[0.48-0.98]), compared to never usage. In the HCUP-NIS, cannabis users had decreased risk for total PUD (aPRR: 0.74[0.61-0.89]), duodenal PUD (0.48[0.35-0.60]) and PUD complications including hemorrhage (0.58[0.37-0.90]), perforation (0.66[0.51-0.87]), but not obstruction (1.75[0.51-5.98]). DISCUSSION/SIGNIFICANCE OF IMPACT: Cannabis usage is related to a reduced likelihood of having HPI in the community and also mitigate against having complicated presentations to the hospital. More translational studies are needed to illuminate the details of this relationship, given the high worldwide prevalence of both cannabis use and HPI.
Large neotheropods from the Upper Triassic of North America and the early evolution of large theropod body sizes
Authors: Griffin Christopher T.
Published: March 2019

Large body sizes among nonavian theropod dinosaurs is a major feature in the evolution of this clade, with theropods reaching greater sizes than any other terrestrial carnivores. However, the early evolution of large body sizes among theropods is obscured by an incomplete fossil record, with the largest Triassic theropods represented by only a few individuals of uncertain ontogenetic stage. Here I describe two neotheropod specimens from the Upper Triassic Bull Canyon Formation of New Mexico and place them in a broader comparative context of early theropod anatomy. These specimens possess morphologies indicative of ontogenetic immaturity (e.g., absence of femoral bone scars, lack of co-ossification between the astragalus and calcaneum), and phylogenetic analyses recover these specimens as early-diverging neotheropods in a polytomy with other early neotheropods at the base of the clade. Ancestral state reconstruction for body size suggests that the ancestral theropod condition was small (~240 mm femur length), but the ancestral neotheropod was larger (~300–340 mm femur length), with coelophysoids experiencing secondary body size reduction, although this is highly dependent on the phylogenetic position of a few key taxa. Theropods evolved large body sizes before the Triassic–Jurassic extinction, as hypothesized in most other ancestral state reconstructions of theropod body sizes, but remained rare relative to smaller theropods until the Jurassic.
Street Food, Urban Space, and Gender: Working on the Streets of Nineteenth-Century Rio de Janeiro (1830–1870)
Authors: Teubner Melina
Published: March 2019

This article focuses on African women (Quitandeiras) who worked in the food sector of the fast-growing port city of Rio de Janeiro during the first half of the nineteenth century. The growing need to supply the harbour workers as well as the crews and captives on the slave ships stimulated the food economy in Rio de Janeiro. The absence of effective government food infrastructure offered opportunities for small businesses. The maritime world on a ship was, in many ways, male. However, there were a high number of female workers in the ports, especially in the informal food sector, frequently mentioned by contemporary authors. This article analyses the involvement of these women as part of a growing working class, who contributed to Rio de Janeiro's crucial role in global networks. The research also focuses on the formation of self-organized groups of female vendors. Thus, it provides further insights into strategies of local actors. By grouping together, the women gained some measure of protection, which empowered them to survive in a difficult and highly competitive market. Through their activities, they also changed the urban space of the port area, leaving their mark on it. They acted as crucial vectors for establishing different diaspora dishes, which met huge demand among many consumers. In doing so, they contributed to the formation of an African-American food culture on the streets of Rio de Janeiro.
Pragmatism, practices, and human rights
Authors: Lamb Robert
Published: March 2019

This article is an intervention in recent debates about conceptual and normative theorisations of human rights, which have been increasingly characterised by a divide between ‘moral’ and ‘practice-based’/’political’ understandings. My aim is to articulate an alternative, pragmatist understanding of human rights, one that is importantly distinct from the practice-based account with which it might be thought affiliated. In the first part of the article, I reveal the fundamental flaw in the practice-based account of human rights: I argue that it is undermined by the ontological thesis at its heart, which naturalises and reifies political arrangements and institutions that are radically contingent. In the second part, I identify, and outline the attractiveness of, a pragmatist normative account of human rights. In contrast to the practice-based approach, this pragmatist account construes human rights in ideational terms. The pragmatist understanding accepts both the contingency of our practices and the cultural limits to moral justification, while nevertheless retaining a commitment to the enterprise of normative philosophical conversation. I argue, in contrast to prevailing interpretations, that the international theory advanced by John Rawls exemplifies a pragmatist account of human rights and points a way forward for theoretically fruitful but appropriately circumscribed analysis of the concept.
The Internet of Things: Both Goods and Services
Authors: CHANDER ANUPAM
Published: March 2019

International trade law, organized around the goods-services dichotomy, is about to meet the Internet of Things (IoT). How will rules written for the world of 1994 fare in a world of talking teapots and connected cars? IoT will especially raise governmental concerns with respect to privacy, security, and standards. Indeed, governments have already begun taking adverse measures against foreign IoT suppliers based not on the hardware, but on the digital features of the products. This paper argues that IoT devices comprise both goods and services, therefore calling into application multiple WTO disciplines, with the specific agreements that are applicable dependent on the particular governmental measure subject to challenge.