bluuebunny/crossref_metadata_2025 huggingface dataset:
2188
Authors: Makowski Nathaniel , Kobetic Rudi , Lombardo Lisa , Foglyano Kevin , Pinault Gilles , Selkirk Stephen , Triolo Ronald
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Evaluate the effect of multijoint functional electrical stimulation (FES) on energy consumption during post-stroke walking. METHODS/STUDY POPULATION: A 67-year-old male with chronic stroke was implanted with an 8-channel implanted pulse generator to stimulate flexor and extensor muscles of the hip, knee, and ankle. Oxygen consumption was measured with a k2b4 portable pulmonary gas analyzer during walking with and without FES assistance. Data were analyzed during steady state oxygen consumption within the last 2 minutes of a 5 minute walk. Distance and walking speed were also measured. RESULTS/ANTICIPATED RESULTS: Electrical stimulation increased walking speed from 0.29 to 0.64 minute/second. Faster walking corresponded with increased oxygen consumption from 10.1 to 14.4 mL O2/kg per minute. Energy cost, consumption as a function of distance, decreased from 3.7 to 2.9 mL O2/kg per minute walking with stimulation compared with without. DISCUSSION/SIGNIFICANCE OF IMPACT: These preliminary data suggest improvements in walking speed with FES are accompanied by increased energy consumption and decreased energy cost. Oxygen consumption during FES assisted walking was <50% of the peak for able bodied individuals of similar age; patients may successfully use the system for community ambulation.
2193
Authors: Alachkar Houda , Mutonga Martin , de Albuquerque Amanda , Deo Rucha , Malnassy Gregory , Nakamura Yusuke , Stock Wendy
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Unlike the high cure rates (90%) of children with acute lymphoblastic leukemia (ALL), that of adults is still lagging behind and better therapies are needed. Maternal embryonic leucine-zipper kinase (MELK) is aberrantly upregulated in cancer, and implicated in cancer stem cell survival. A recent study has identified FOXM1, a MELK substrate, as a therapeutic target in B cell ALL (B-ALL). Thus, we hypothesized that MELK may act as a therapeutic target in ALL via targeting FOXM1 activity. METHODS/STUDY POPULATION: Western blot and qPCR were used to assess MELK expression in 14 ALL cell lines. Knock-down and kinase inhibition approaches targeting MELK expression and function, followed by CCK-8 and Annexin V (flow cytometry) assays to measure cell viability and apoptosis, respectively. RESULTS/ANTICIPATED RESULTS: MELK was significantly upregulated in patients with ALL (oncomine data analysis). MELK was also significantly higher in B-ALL and T-ALL cell lines compared with that in blood cells of healthy donors. MELK knock-down significantly decreased cell viability (40%–70%, p<0.05, Fig. 1) in ALL cells, and induced apoptosis (~40%). OTS167, a potent MELK inhibitor exhibited cytotoxic activities in both B and T-ALL cells. The IC50 of OTS167 ranged from 20 to 60 nM; we also found a significant increase in apoptosis (p<0.05). Mechanistically, MELK inhibition resulted in decrease of FOXM1 protein levels 3 hours post-treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: MELK is highly expressed in ALL and represents a novel therapeutic target likely via modulating FOXM1 activity. Functional and mechanistic studies will complement and ensure the success of the undergoing Phase I/II clinical trial of OTS167 in patients with refractory or relapsed AML, ALL, and other advanced hematologic malignancies.
2210
Authors: Burke Sarah Elizabeth , Samuel Immanuel B. H. , Zhou Qing , Kluger Benzi , Price Catherine , Ding Mingzhou
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Identify objective neurological substrates of cognitive fatigue in Parkinson’s disease and in aging. METHODS/STUDY POPULATION: Structural and diffusion MRI. Behavioral assessments for aged adults and Parkinson’s disease. RESULTS/ANTICIPATED RESULTS: Gray and white matter deficits that correlate with deficits in the basal ganglia for fatigued Parkinson’s disease patients Versus anterior cingulate cortex in healthy aged adults with fatigue. DISCUSSION/SIGNIFICANCE OF IMPACT: Over 50% of patients with Parkison’s disease and 38% of healthy older adults suffer from cognitive fatigue. However, diagnostics are limited to subjective surveys and there are no treatments for either population. Therefore, objective measures are greatly needed for better diagnosis and development of treatment targets.
2251
Authors: Lee Frump Andrea , Albrecht Margie , Breuils-Bonnet Sandra , Yakubov Bakhtiyor , Beth Brown Mary , Provencher Steeve , Bonnet Sebastien , Lahm Tim
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Women with pulmonary arterial hypertension (PAH) exhibit superior right ventricular (RV) function and survival compared with men, a phenomenon attributed to poorly understood cardioprotective effects of 17β-estradiol (E2). We hypothesize that E2, through ERα, attenuates PH-induced RV dysfunction by upregulating the pro-contractile and pro-angiogenic peptide apelin. This ERα-mediated increase in apelin is mediated by the myocardial remodeling effector bone morphogenetic protein receptor 2 (BMPR2). METHODS/STUDY POPULATION: ERα, BMPR2, and apelin were measured (western blot) in RVs from patients with PAH-induced RV failure and in RV homogenates from male or female Sprague-Dawley rats with sugen/hypoxia (SuHx) or monocrotaline (MCT)-induced PH. H9c2 rat cardiomyoblasts and cardiac endothelial cells were stressed with TNF-α (10 ng/mL) or staurosporine (50 nM)±E2 (100 nM; 24 h). ERα-, BMPR2-, and apelin-dependence were evaluated by siRNA (5 pM). Downstream apelin target and pro-survival factor ERK1/2 expression was measured (western blot). p<0.05 by ANOVA was considered significant. RESULTS/ANTICIPATED RESULTS: ERα correlated positively with BMPR2 and apelin expression in SuHx-RVs and human RVs. Treatment of SuHx-PH rats with E2 or ERα agonist increased RV BMPR2 and apelin, whereas RV apelin was decreased in E2-treated hypoxic ERα knockout mice (p<0.05), but not in ERβ knockout mice. In H9c2 cells, E2 or ERα agonist attenuated TNF-α- or staurosporine-induced decreases in BMPR2, apelin, and phospho-ERK1/2 (p<0.05 for all endpoints). E2 protection was lost in presence of siRNA directed against ERα, BMPR2, or apelin (p<0.05). ERα was necessary for E2-mediated increases in BMPR2, apelin, and ERK1/2, and BMPR2 was required for the E2-mediated increase in apelin (p<0.05 for siRNA vs. scramble). ERα, BMPR2, and apelin protein was increased in decompensated human RVs but downstream phospho-ERK signaling was disrupted. DISCUSSION/SIGNIFICANCE OF IMPACT: E2, via ERα, increases BMPR2 and apelin in the failing RV and in stressed rat cardiomyoblasts. The E2-mediated increase in apelin is BMPR2-dependent and likely occurs through direct binding of ERα to the BMPR2 promoter. Harnessing this E2-ERα-BMPR2-apelin axis during RV compensation may lead to novel, RV-targeted therapies for PAH patients of either sex.
2281
Authors: Yavuz Metin , Ersen Ali , Adams Linda
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: According to the US census, there are 3.3 million Americans who have to use wheelchairs in order to maintain their mobility. About 50% of these patients develop a pressure ulcer at some point during their life time. Three major factors contribute to pressure ulceration; pressure, tissue temperature, and maceration due to sweating. The objective of this study is to develop a temperature regulating wheelchair cushion in order to address elevated tissue temperatures and related sweating. METHODS/STUDY POPULATION: We instrumented a wheelchair with cooling elements, a water filled cushion and a pump. The pump moves the water through the cooling elements where water temperature drops down to 15°C. The water then moves to the cushion where it cools the tissue and then back to the cooling elements. RESULTS/ANTICIPATED RESULTS: We recruited 1 healthy subject to sit on the instrumented wheelchair and then obtained thermographs of the cushion surface using an infrared thermal camera. After 1 minute of sitting on the cushion the minimum temperature was recorded as 27°C. After 10 minutes the temperature dropped to 23.3°C. DISCUSSION/SIGNIFICANCE OF IMPACT: In this ongoing proof-of-concept study we are investigating if circulating chilled water inside a wheelchair cushion is a feasible method to regulate tissue temperatures at the 25–28°C range. This range has been shown to delay ulceration under loading conditions that simulate sitting on a wheelchair. Initial results indicate that this may be an effective ulcer prevention method.
2392
Authors: Choudary Ahsan , Bishop Andrew C. , Misra Biswapriya , Libardoni Mark , Lange Kenneth , Bernal John , Nijland Mark , Li Cun , Nathanielsz Peter W. , Olivier Michael , Cox Laura A.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to use the baboon as a novel animal model for breath research and to identify and characterize baboon breath metabolites that reflect cardiometabolic function to inform us in the development of a noninvasive, cost-effective, and repeatable point-of-care diagnostic breath test. METHODS/STUDY POPULATION: Blood and urine was collected from control and IUGR at the approximate age of 3.5 years. Both groups were then placed on a high fat, high sugar, high salt diet for 7 weeks, after which blood, urine, and breath were collected. The breath samples were then subjected to comprehensive, 2-dimensional gas chromatography coupled with time-of-flight mass spectrometry. Using ChromaTOF software, breath VOCs were identified with at least an 80% spectral match against the National Institute of Standards and Technology (NIST) chemical reference library. The raw data were then statistically analyzed using MetaboAnalyst. We then interrogated multiple online databases to characterize and identify the role of VOCs that were present in both control and IUGR groups. RESULTS/ANTICIPATED RESULTS: Preliminary analyses of the breath VOCs indicate differences in expression between sexes and in control Versus IUGR groups. These results indicate unique “breath signatures.” Further analysis of the breath VOCs reveals the presence of metabolites that are involved in β-oxidation and oxidative stress pathways. DISCUSSION/SIGNIFICANCE OF IMPACT: This breath study, a first of its kind, will develop the baboon as a superior animal model for breath biomarker research. Our observed unique “breath signatures” indicate changes in lipid metabolism and oxidative stress pathways, which we hypothesize are the early metabolic changes at the cellular level that are not yet reflected in clinical lab measures. Future directions include analyzing breath VOCs that did not meet 80% spectral match, validation using SPME technology and commercial standards, and initiating a human pilot study in clinically obese, at-risk children in collaboration with physicians at the Children’s Hospital of San Antonio to develop a noninvasive, cost-effective, rapid, and repeatable point-of-care diagnostic breath test.
2153
Authors: Benhabbour Rahima , Janusziewicz Rima , Mecham Sue J. , Shrivastava Roopali , Paravyan Gayane
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The long-term goal of this project is to develop a cost effective 3D printed multipurpose intravaginal ring (IVR) to prevent against unintended pregnancies and infectious diseases.Our goal is to develop a female-controlled method for prevention using innovative IVRs. METHODS/STUDY POPULATION: In vitro and in vivo characterization. RESULTS/ANTICIPATED RESULTS: Controlled and fine-tuned release kinetics 100% drug release from 3D printed IVRs compared with 10%–15% with traditional injection molded IVRs cost-effective engineering of multipurpose IVR with CLIP 3D printing technology. DISCUSSION/SIGNIFICANCE OF IMPACT: If successful, this project will revolutionize the engineering of IVRs and will have a global impact on human health. Not only we will help save millions of women around the world but also millions of children that are infected by their HIV-positive mothers through gestation or breast feeding.
2399
Authors: Garcia Robles Franchesca , DeJesus Nilka , Barrios Nilka
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Determine whether children with solid tumors maintain intact protective immunity to live vaccines during cancer therapy and after completing cancer therapy (postTx). METHODS/STUDY POPULATION: We will perform a prospective cohort study of children with solid tumors (Hodgkin lymphoma, brain, Wilms, and germ cell tumors) followed at the Puerto Rico’s University Pediatric Hospital. Protective immunity will be measured with antibody titers against live vaccines (Measles, Mumps, Rubella, and Varicella) at diagnosis, during cancer therapy, upon completion and 3 months postTx. RESULTS/ANTICIPATED RESULTS: We hypothesize that those patients with protective immunity to live vaccines prior to cancer therapy will lose it at the end of therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: Loss of protective immunity to live vaccines has been reported in patients with hematologic malignancies after cancer therapy. This lack of protective immunity, which puts patients at higher risk of acquiring vaccine preventable diseases, has been limited studied in patients with solid tumors. The Center for Diseases Control has been established that it is safe to immunize cancer survivors with live vaccines 3 months post Tx. However, no clear guidelines for revaccination have been provided for this population. Understanding the protective immunity variation against live vaccines in children with solid tumors will allow us to identify the need for revaccination with live vaccines in this vulnerable population.
2169
Authors: Wen Jingran , Scoles Daniel , Facelli Julio C.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Polyglutamine (polyQ) neurodegenerative diseases, associated with the unstable expansion of polyQ tracts, are devastating diseases for which no treatments exist. Moreover, most drug discovery attempts have been hindered by the lack of understanding on the relevant pathogenic mechanisms. Here, using previously reported 3D protein predicted structures of ataxin-2 and ataxin-3, we analyze the effect of polyQ enlargement on hydrogen bonding and water accessibility patterns as a possible mechanism for pathogenesis thought enhanced protein aggregation. METHODS/STUDY POPULATION: Using the I-TASSER predicted structures of ataxin-2 and ataxin-3 with different numbers of glutamine repeats representing polyQ lengths characteristic of both normal and pathological tracts (Journal of Biomolecular Structure and Dynamics, 2016: 1–16), we identified hydrogen bonds (HBs, UCSF Chimera FindHBond module) and calculated solvent-accessible surface areas (SASA, DSSP program) for the polyQ tracts available in the 3D structures. RESULTS/ANTICIPATED RESULTS: The identified HBs were analyzed as the function of the number of glutamines in the polyQ tracts and characterized as those intra-polyQ and exter-polyQ, respectively. The SASA of the polyQ region was also studied as the function of the polyQ tract length. DISCUSSION/SIGNIFICANCE OF IMPACT: The results obtained here indicate that polyQ regions increasingly prefer self-interactions, which consistently can lead to more compact polyQ structures. The results strongly support the notion that the expansion of the polyQ region can be an intrinsic force leading to self-aggregation of polyglutamine proteins and suggest that the modulation of solvent-polyQ interactions could be a possible therapeutic strategy for polyQ diseases.
2135
Authors: Kanzler Kathryn E. , Robinson Patricia , Munante Mariana , McGeary Donald , Potter Jennifer , MacIntyre Bria , Lopez Eliot , Hale Willie , Mintz James , Velligan Dawn
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: This study seeks to test the feasibility and effectiveness of a brief acceptance and commitment therapy (ACT) treatment for chronic pain patients in a primary care clinic METHODS/STUDY POPULATION: Primary care patients aged 18 years and older with at least 1 pain condition for 12 weeks or more in duration will be recruited. Patients will be randomized into (a) ACT intervention or (b) control group. Participants in the ACT arm will attend 1 individual visit with an integrated behavioral health provider, followed by 3 weekly ACT classes and a booster class 2 months later. Control group will receive enhanced primary care that includes patient education handouts informed by cognitive behavioral science. Data analysis will include 1-way analysis of covariance (ANCOVA), multiple regression with bootstrapping. RESULTS/ANTICIPATED RESULTS: The overall hypothesis is that brief ACT treatment reduces physical disability, improves functioning, and reduces medication misuse in chronic pain patients when delivered by an integrated behavioral health provider in primary care. In addition, it is anticipated that improvements in patient functioning will be mediated by patient change in pain acceptance and patient engagement in value-consistent behaviors. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study will establish preliminary data about the effectiveness of addressing chronic pain in a generalizable integrated primary care setting. Data will help support a larger trial in the future. Findings have potential to transform the way chronic pain is currently managed in primary care settings, with results that could decrease disability and improve functioning among patients suffering from chronic pain.
2147
Authors: Ying Guo Stacey , Whitson Heather , Ostbye Truls , Luciano Alison , Malhotra Rahul
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To investigate whether medical complexity (indicated by multiple providers or healthcare visits) is associated with lower levels of confidence in medication use and lower medication adherence METHODS/STUDY POPULATION: Data on socio-demographics, health encounters, health status, and health attitudes and behaviors from a nationally representative sample of 1575 older Singaporean adults were utilized. The association of medical complexity factors with self-reported medication confidence and adherence was analyzed using logistic regression analysis controlling for age, gender, ethnicity, education, and number of health conditions. RESULTS/ANTICIPATED RESULTS: The survey had a 60% response rate. The mean age of respondents was 72, and 42% were male. We found no significant association between number of visits and either confidence about usage (OR=1.07, 95% CI 0.95–1.20) or medication adherence (OR=1.01, 95% CI 0.90–1.13). We similarly found no significant association between number of providers and either confidence about usage (OR=1.03, 95% CI 0.90–1.18) or medication adherence (OR=1.05, 95% CI 0.93–1.20). Lower confidence about medication use was less likely among males (OR=0.60, 95% CI 0.44–0.80), those with more education (OR=0.29, 95% CI 0.20–0.42) or more comorbidities (OR=0.89, 95% CI 0.82–0.96) and more likely with increasing age (OR=1.06, 95% CI 1.04–1.08). Nonadherence was more likely among Indians (OR=1.62, 95% CI 1.06–2.48) and those with more comorbidities (OR=1.10, 95% CI 1.02–1.18). DISCUSSION/SIGNIFICANCE OF IMPACT: Having more healthcare visits or providers were not independent correlates of lower medication confidence or adherence. Seniors with less education may benefit from interventions to improve confidence about medication use. Participants with more comorbidities expressed greater confidence but admitted to lower adherence. The role of other potential contributors to nonadherence in complex patients (eg, cost and access, patient preference, competing demands) should be evaluated next.
2190
Authors: Nearing Kathryn , Nease Donald , Tamez Montelle M. , Tenney Martha , Sweitzer Elizabeth
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: (1) Provide an innovative tool used to accelerate and evaluate T3-T4 research; (2) describe the collective capacity building tool (CCBT) methodology—both programmatic and evaluative applications; and (3) share insights about the process and outcomes of community-engaged research. METHODS/STUDY POPULATION: Academic and community-based partners complete the assessment together at the beginning and conclusion of their Community Engagement pilot projects. Further, they are encouraged to use the tool and the associated insights/priorities that emerge as the basis for data-driven coaching with Community Research Liaisons throughout the 12-month grant cycle. RESULTS/ANTICIPATED RESULTS: Pre/post results with 4 cohorts of pilot grantees consistently demonstrated the most positive change in relation to 1 item: overcoming previously identified barriers to community engagement (eg, language, mistrust, scheduling conflicts). Other key findings: (1) networks of reciprocal ties expand, providing structures to support dissemination of information and interventions. (2) Partners leverage expanded networks to pursue follow-on funding and extend the scope/reach of their efforts geographically and/or with new populations. (3) Projects enhance trust in the research process by developing group processes that facilitate the respectful sharing of diverse (often alternative) viewpoints and through culturally-responsive project implementation. DISCUSSION/SIGNIFICANCE OF IMPACT: The CCBT can be used at multiple points in time to help project partners achieve the deliberate integration of CBPR principles in practice and advance community-engaged translational research efforts for sustainability and scalability. The CCBT is sensitive enough to document the iterative nature of partnership development and CBPR. An example: a great deal of variability was found in how formally partners defined roles. Further, partner roles often changed as projects evolved. Still, results indicated a general trend toward achieving greater clarity in partner roles over time. Further, the tool captured set-backs due to partner turn-over and partnerships regaining momentum after new staff came on board. Results have strong face validity: more mature partnerships reported stronger community connections and previous successes to build upon. Perhaps most importantly: the tool and associated process was well-received by academic and community-based partners alike.
2191
Authors: Ronis Sarah , Stange Kurt , Kleinman Lawrence
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: (1) To propose an iterative decision-making model of care planning for CSHCN. (2) To identify targets warranting measurement in future studies of SDM in care planning for CSHCN. METHODS/STUDY POPULATION: Conceptual model developed by a multidisciplinary team iteratively considering the complex relationships among diverse factors affecting care planning for CSHCN, informed by clinical and implementation science experience and a scoping literature review of medical and cognitive sciences literature addressing interpersonal decision-making, communication, negotiation, and trust among children, their parents, and their clinicians. RESULTS/ANTICIPATED RESULTS: Decision-making interventions in pediatrics tend to focus narrowly on single acute decisions, providing minimal guidance for decisions related to chronic disease management over time. Few models account for the role of the child in the decision-making process, despite their ongoing development. Therefore, we propose a model of shared decision-making in the context of managing chronic illness in children that recognizes all actors and can support both the design of clinical care and research. This model—The SDM Learning Loop Model—highlights the dynamic iterative nature of exchanges between and among the clinical team and the parent-child dyad and recognizes the child as the center of each decision-making cycle. The model accounts for key practice, family, experiential, and emotional contexts influencing the decision-making encounter. In this model, change in child health status and developmental capacity resulting from a given cycle’s care plan will directly influence the relationship between clinician and parent-child dyad (eg, mutual trust, attunement) and impact each party’s engagement in the next round of decision-making. The relationship between experience and outcome stimulates learning. DISCUSSION/SIGNIFICANCE OF IMPACT: Our proposed SDM Learning Loop Model suggests that increasing the shared nature of decision making is not only likely to optimize care planning, but creates “buy-in” that can both reinforce the impact of positive outcomes, and moderate the negative impact on relationships when the outcome is other than desired. We hypothesize that this model can guide care planning and shape research to the benefit of both clinical outcomes and clinician-family relationships. Future work should focus on the development and validation of measures to account for the experiential and emotional contexts in which such decisions are made, and the outcomes of care in this population.
2261
Authors: Liao Albert , Carlson Grant W. , William Eley John , Gillespie Theresa W.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Evidence-based guideline-concordant care leads to better outcomes in patients with early stage breast cancer, including survival. However, previous studies of guideline compliance have been limited by small study sample sizes, localized geography, unknown causal factors, and lack of diverse population. We use a national database to assess socio-economic, clinical, and facility factors that impact treatment compliance with evidence-based guidelines from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN). METHODS/STUDY POPULATION: This is a retrospective cohort study of the National Cancer Data Base Participant User File Breast 2014, which captures ~70%–80% of all newly diagnosed cancer cases in the United States. Female patients who were diagnosed with early stage breast adenocarcinoma (T0, T1, T1A, T1B, 2, 2A, or T2N1) from 2004 to 2014 were eligible for this study. RESULTS/ANTICIPATED RESULTS: A total of 807,314 patients were included in this study. Evidence-based guidelines examined with associated compliance rates include surgery completion (79.3% overall compliance), breast conserving surgery Versus mastectomy (88.05% vs. 11.95%, respectively), radiation after breast conserving surgery (77.5% overall compliance), HER2 testing (88.6% overall compliance), estrogen/progesterone receptor (ER/PR) testing (96.3% overall compliance), hormone treatment for positive ER/PR breast cancer (80.2% overall compliance), and sentinel lymph node biopsy completion (67.5% overall compliance). Univariate association between these guidelines and covariates such as facility type, facility location, age, race, insurance status, median income quartiles, achievement of high school degree, urban Versus rural, Charlson-Deyo score, year of diagnosis, and overall survival were assessed. Logistic regression analysis will be used to determine multivariate relationships between these characteristics and the probability that a patient will be compliant to guideline regimen. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study will help identify socio-economic, clinical, and facility factors that influence guideline-concordant care and subsequent critical outcomes for patients with early stage breast cancer. Lack of guideline concordant care for specific stages of cancer or treatment modalities will point to a need for tailored interventions to enhance compliance. A prediction model will help identify the most important predictors of noncompliance in breast cancer treatment so noncompliance can be prevented in at-risk populations.
2414
Authors: Altieri Pablo I. , Figueroa Alejandro , Valle Ismael , Arce Orlando , Colon Brigida , Banchs Hector , Altieri Pablo
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: A retrospective analysis was done at the Cardiovascular Center to evaluate reperfusion strategies, including stemi infarcts and non-stemi classified as stemi in a period of 2 years. METHODS/STUDY POPULATION: Review the records of stemi infarcts in a period of 2 years. RESULTS/ANTICIPATED RESULTS: In total, 101 cases were classified as stemi, but after strict analysis (time wise) 24 cases were non-stemi; 47% had inferior myocardial infarction and 38% an anterior myocardial infarction with a mean age of 65 years. All cases were immediately catheterized. Although the non-stemi, classified originally as stemi did not meet the time limit (<2 h) for cath. The stemi group (77 P.) 58 P. had angioplasty with stent implantation. 19 P. had an EF of 45% and remained that way during follow up. The rest of the P. the EF went up to 50% or more. The non-stemi group (24 P.) had angioplasty with stent implantation. The EF remained around 40% during follow up, which was the EF on admission. Fibrinolysis was given erratically. No changes were seen in the EF on follow up in the fibrinolytic group. DISCUSSION/SIGNIFICANCE OF IMPACT: This shows the importance of classifying the P. well between stemi and non-stemi. The time frame to catheterization should be kept as strict as possible, due to transmural infarcts, and catheterized in <2 hours to avoid deterioration of the left ventricular function and its consequences. This strict classification will save money to the institution when emergency catheterization is avoided in the non-stemi group.
2423
Authors: Cohen Scott , Mack Jasmine , Striley Catherine , Cottler Linda
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Research on social determinants of health (SDHs) in type 2 diabetes have largely examined disease etiology rather than severity. To find factors associated with complications, we investigated socio-demographics, healthcare access, and healthcare utilization in individuals with type 2 diabetes with respect to related comorbidity. METHODS/STUDY POPULATION: Community health workers assessed 8494 participants for type 2 diabetes (n=939; 11%) through HealthStreet, a community-engagement model implemented in North Central Florida. Comorbidities were defined as neuropathy, retinopathy, high cholesterol, hypertension, and kidney failure. We conducted multivariate analyses to test the association of socio-demographic factors and comorbidity status. RESULTS/ANTICIPATED RESULTS: Of 939 members with type 2 diabetes, 164 (17%), 272 (29%), 370 (39%), and 133 (14%) reported having 0, 1, 2, and 3+ comorbidities, respectively. There is a smaller proportion of African-Americans reporting 3+ comorbidities compared with other comorbidity groups (p=0.003). Those with more comorbidity are less employed (p<0.0001) and are more likely to have Medicare/Medicaid (p=0.03) than those without comorbidity. Those with no comorbidity are more likely to be uninsured compared to those with comorbidity (p=0.0297). Adjusting for age, race, gender, and BMI, those that have at least 1 comorbidity are 1.4 times more likely to be food insecure (p=0.004) and are 1.9 times more likely to have seen a doctor in the past 12 months (p=0.002) compared to those without comorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: Although there is complexity among the relationships between SDHs and diabetic comorbidity, results suggest significant sociodemographic and healthcare-related disparities among individuals living with type 2 diabetes. Members with more comorbidity utilize healthcare, but are more likely to be food insecure among other factors. Those with no comorbidity are least likely to see a physician, which could imply a gap in the care continuum. This analysis gives insight into the importance of efficient diabetes management, focused on disparities in economic stability and healthcare access and utilization.
2452
Authors: Srivastava Arnav , Joice Gregory , Manka Madeline , Sopko Nikolai , Jamie Wright Edward
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Stress urinary incontinence (SUI) significantly affects quality of life and occurs in 60% of men after radical prostatectomy, with 5% requiring surgical treatment. The artificial urinary sphincter (AUS) offers these patients excellent control of their post-prostatectomy SUI. The device contains 3 parts: the pump, urethral cuff, and pressure regulating balloon. Despite the effectiveness of AUS, up to 50% of patients require surgical revision after initial placement due to recurring SUI. Thus far, literature is heterogeneous regarding the causes of mechanical AUS failure and appropriate surgical management. Our study aims to characterize the most common reasons of AUS failure requiring surgical revision and the survival of each AUS component. METHODS/STUDY POPULATION: We report a series of 48 patients who received AUS placement and/or revision by 1 surgeon from 2010 to 2013. Upon presenting for revision, intraoperatively, the surgeon systematically evaluated the device for failure of the balloon, cuff and pump as well as urethral erosion and atrophy. In patients not requiring revision all device components were presumed functional. We conducted retrospective chart review to collect baseline characteristics, intraoperative findings, and postoperative outcomes. Using Kaplan-Meier estimates, we calculated incidence rates of component failure for the cuff, pump, and balloon. To identify risk factors for AUS failure, Cox regression was performed for univariate and multivariable testing. Multivariable modeling included those variables considered biologically plausible and significant in univariate testing. RESULTS/ANTICIPATED RESULTS: In total, 48 patients were studied with median follow up of 4.25 years. All patients received an AMS 800 device with a 61–70 mL balloon filled with 27 cc of isotonic contrast. Cuff sizes ranged from 3.5 to 5.5 cm, with 4.5 cm selected in 33/48 cases (68.8%); 19 of the patients required AUS correction (41.7%). Balloon leak constituted 57.9% (11/19) of failures, followed by cuff failure/urethral atrophy (21.1%), urethral erosion (10.5%), and individual cases of infection and pump failure. Median time to mechanical failure due to balloon leak was 3.67 years (IQR 2.17, 5.33); median time to failure for nonballoon causes was 0.54 years (IQR 0.25, 1.83). Survival of the balloon, cuff, and pump was 100%, 95.7%, and 97.9% at 1 year and 76.9%, 91.0%, and 97.9% at 5 years, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study identifies fluid leakage from the balloon as the most common cause of AUS failure, particularly in patients presenting between 1 and 5 years after initial placement. For such patients, interrogating the balloon first can decrease infection risk and surgical morbidity as it can avoid manipulation of the urethral cuff. Furthermore, simply replacing lost fluid saves cost and allows for immediate reactivation of the AUS device.
2215
Authors: Moran Timothy P. , Immormino Robert M. , Nakano Hideki , Peden David , Cook Donald N.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Allergic asthma is a chronic lung disease driven by inappropriate inflammatory responses against inhaled allergens. Neuropilin-2 (NRP2) is a pleiotropic transmembrane receptor expressed in the lung, but its role in allergic airway inflammation is unknown. Here, we characterized NRP2 expression in lung immune cells and investigated the effects of NRP2 deficiency on airway inflammation. METHODS/STUDY POPULATION: NRP2 expression by lung immune cells from NRP2 reporter mice was determined by flow cytometry. NRP2 expression by human alveolar macrophages (AM) from healthy individuals was determined by mRNA analysis and flow cytometry. Airway inflammation in NRP2-deficient mice was assessed by bronchoalveolar lavage (BAL) cytology and inflammatory gene expression in lung tissue. RESULTS/ANTICIPATED RESULTS: NRP2 expression in lung immune cells was negligible under steady-state conditions. In contrast, inhalational exposure to lipopolysaccharide (LPS) adjuvant dramatically induced NRP2 expression in AM, as 63.3% of AM from LPS-treated mice were NRP2+ compared with 1.5% of AM from control mice. Ex vivo treatment of human AM with LPS resulted in a 1.5-fold and 2.6-fold increase in NRP2 mRNA and surface protein expression, respectively. Compared to littermate controls, NRP2-deficient mice had greater numbers of BAL leukocytes and increased lung expression of the T helper type 2 cytokines IL-4 and IL-5. Furthermore, NRP2 deficiency resulted in stochastic development of allergic airway inflammation, as spontaneous airway eosinophilia was detected in 25% (2/8) of NRP2-deficient mice compared with 0% (0/8) of littermate controls. DISCUSSION/SIGNIFICANCE OF IMPACT: NRP2 is expressed by activated human and murine AM and suppresses the spontaneous development of allergic airway inflammation. These findings suggest that NRP2 may play a key role in allergic asthma pathogenesis, and could prove to be an important therapeutic target in patients with asthma and other allergic diseases.
2538
Authors: Srivastava Arnav , Joice Gregory , Manka Madeline , Sopko Nikolai , Wright Edward
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Perineal urethral sling placement is an option for men with mild to moderate post-prostatectomy stress urinary incontinence (SUI). However, men with persistent incontinence after sling placement often require secondary artificial urinary sphincter (AUS) placement, made difficult by the sling occupying the proximal bulbar urethra. This proximal section has a thicker corpus spongiosum which may mitigate cuff-induced ischemia and subsequent urethral atrophy. The authors report a series of AUS placements after failed sling, using sling revision or removal to access the proximal urethra. METHODS/STUDY POPULATION: Cutting the sling arms during urethral cuff placement increased urethral exposure and mobility. If feasible, completely removing the sling allowed the most proximal cuff site; but if dissection was felt unsafe, the mesh was left in situ and the cuff placed distally. This study is a retrospective cohort design of patients with SUI who underwent AUS placement after failed sling from 2010 to 2016. Variables included baseline patient characteristics, SUI severity, intraoperative variables, and postoperative outcomes. AUS failure, defined as infection, erosion or urethral atrophy, was analyzed at 12 and 96 months using univariate and multivariable logistic regression. RESULTS/ANTICIPATED RESULTS: Over the study period, 29 patients underwent AUS placement after failed sling. At the time of AUS placement, mean urethral circumference was 6.2 cm and 68% of patients had a 4.5 cm cuff placed; no cases required a 3.5 cm cuff. Seventy-three percent of cases were after transobturator sling placement (27% bone-anchored) and 45% of slings were explanted. AUS failure rate at 12 and 96 months was 17.8% and 45%, respectively; atrophy was the most common indication. Prior transobturator sling placement had lower rates of both 12 month (9.1% vs. 57%, p=0.006) and 96 month (36% vs. 71%, p=0.11) failure, though the latter was not statistically significant. Sling explant was not a significant predictor of 12 month (p=0.12) or 96 month failure (p=0.17). DISCUSSION/SIGNIFICANCE OF IMPACT: Sling revision during AUS placement helps expose the wider proximal urethra, allowing larger cuff size placement. This procedure appears safe, with low rates of erosion and short-term failure—albeit with high rates of long-term urethral atrophy possibly due to more significant dissection causing devascularization. However, sling removal was not a significant predictor of failure. The transobturator sling’s smaller profile may result in less trauma to urethra—possibly explaining the improved outcomes.
2295
Authors: Sultana Habbsa Samima , McKinstry Mia , Payne Sara , Mosimann Christian , Bowman Teresa
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Hematopoietic stem and progenitor cells (HSPCs) function to maintain steady state production of new blood cells and to rapidly respond to blood cell loss. Little is known regarding how HSPCs develop the ability to sense and respond to blood cell loss during embryogenesis. Gaining insight into the robust ability of HSPCs to regenerate blood during early development may allow us to develop therapies to rejuvenate this capacity at any stage. METHODS/STUDY POPULATION: We generated a new hematopoietic-specific and inducible cell ablation zebrafish model to uncover the origins of regenerative capacity in HSPCs during development. These transgenic zebrafish express a cyan fluorescent protein (CFP)-nitroreductase (NTR) fusion construct under the control of the draculin (drl) promoter (drl:CFP-NTR), which restricts NTR expression to blood cells. Co-expression analyses of drl:CFP-NTR with known markers of other blood types including HSPCs (runx1+23:mCherry), erythroid cells (gata1:dsRed), and lymphoid cells (rag2:RFP), revealed drl:CFP-NTR was restricted to HSPCs and erythrocytes. To delineate the regeneration potential of embryonic HSPCs, we exposed drl:CFP-NTR transgenic zebrafish embryos to Metronidazole (MTZ), which results in selective ablation of only NTR-expressing blood cells. Embryos were treated from 2 to 3 days postfertilization and recovery of drl+ and gata1+ cells was evaluated over a 7-day recovery period. RESULTS/ANTICIPATED RESULTS: Following MTZ exposure, the nadir of drl+ cell ablation occurs at 2 days post MTZ (dpM) treatment. During the renewal phase of blood regeneration, we first observe recovery of drl+ cells by about 4 dpM, while more mature blood cells like gata1+ erythrocytes show a delayed recovery at about 6 dpM. Our results suggest that HSPCs can respond to injury as early as 2 days of life and that the HSPC-driven regeneration of embryonic blood cells occurs in a hierarchical fashion, similar to regeneration of the adult blood system. DISCUSSION/SIGNIFICANCE OF IMPACT: We have established a quantitative method for in vivo real-time monitoring of embryonic and larval blood regeneration. A significant advantage of our system is that we can use these insights to guide an in-vivo drug screen for factors that accelerate HSPC-driven blood regeneration in a complex biological environment.
2350
Authors: Koutzoumis Dimitri , Antonio Pino Jose , Harris Sharonda S. , Quiroz Marisol , Mohamadzadeh Mansour , Enrique Torres Gonzalo
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Several clinical studies have established a correlation between changes in relative bacterial populations in the gut and Parkinson disease. However, few published experiments have been able to parse out whether these associations are causative or correlative. Our aim is to determine how bacteria in the gut may impact the health and resilience of dopaminergic signaling. Our experiment is designed to serve as a proof-of-principle that controlled alterations to the gut microbiome alters mechanisms in dopamine homeostasis in the midbrain. METHODS/STUDY POPULATION: Bacterial inoculation 8–10-week-old germ-free male mice (C57BL/6) were exclusively used in this experiment. Mice were orally gavaged every 3 days (D0, 3, 6, and 9) with 100 µL novel bacterial suspension (~108 CFU resuspended in PBS with 1.5% NaHCO3) or vehicle and were sacrificed on D11. Tissue preparation—brains were quickly extracted and the striatum was isolated and homogenized in either RIPA buffer with protease inhibitors (for Western blot analysis) or in 0.1 N HClO4 (for HPLC processing). The homogenates were processed through fractional centrifugation to remove cellular debris. Lysate samples were frozen at −80°C until ready for analysis. Protein expression quantification—expression of proteins were measured using intensity of bands from Western blots. Lysates were denatured prior to loading with LB with 10% β-mercaptoethanol and 30-minute incubation at 37°C. All immunoblots were normalized to immunoreactivity to α-tubulin. Immunoblot intensity was determined using the ImageJ software. Dopamine/dopamine metabolite quantification HPLC analysis was used to determine dopamine and dopamine metabolite concentration. Aliquots of the lysate were injected onto a C18 column using a mobile phase consisting of 50 mM H2NaO4P·H2O, 0.72 mM sodium octyl sulfate, 75 µM Na2 EDTA, and 10% acetonitrile (pH 3.0). The mobile phase was pumped through the system at 0.3 mL/minute. RESULTS/ANTICIPATED RESULTS: Measured total dopamine concentration through HPLC analysis in the striatum showed no significant differences in the bacteria-treated group relative to the control group. The metabolites DOPAC and HVA had an elevated measured concentration in the bacteria-treated group relative to the control group. Western blot analysis showed decreased immunoreactivity for DAT and TH in the bacteria-treated group compared with the control group. There was no significance difference in the immunoreactivity for VMAT2. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that dopamine signaling dynamics in the midbrain can be altered by changes in the gut flora in mice. These results further substantiate the impact of the gut-brain axis and may even point to a potential avenue of bolstering the resilience of dopaminergic neurons in preventing the onset of PD. Further experiments must be performed to understand the mechanism of the observed changes and to determine if these changes have any salutary effect.
2373
Authors: Kinley-Cooper Serena-Kaye , Adkins DeAnna
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The objectives of this study are to determine whether high-frequency ipsi-lesion or low-frequency contra-lesion ECS improves forelimb function following experimental stroke in aged animals with focal and large strokes. We also want to investigate whether ECS-induced improvements in motor function are related to an enhancement of neural structural plasticity (dendrites and synapses) and changes in growth promoting (BDNF) and growth inhibiting (NOGO-A) expression in the infarcted motor cortex in young and aged animals. METHODS/STUDY POPULATION: We will investigate whether excitatory ECS of the infarcted cortex or inhibition of the noninfarcted cortex combined with daily impaired-forelimb rehabilitative training (RT) results in greater motor functional recovery compared to RT alone. Immunohistochemical (IHC) analyses and unbiased stereological techniques will be performed to investigate changes in proteins associated with dendritic restructuring (MAP2), synaptic plasticity (PSD95 and synaptophysin), and alteration in the expression of BDNF and NOGO-A. RESULTS/ANTICIPATED RESULTS: We expect that inhibitory ECS of the noninfarcted motor cortex will improve behavioral outcomes in moderate to severe stroke animals compared with excitatory ECS or no stimulation (RT alone) animals. We predict that the ECS condition that improves motor performance most significantly compared with RT alone will have a corresponding greater increase in remaining ipsi-infarct motor cortical dendritic and synaptic plasticity (demonstrated by a greater density of MAP2, synaptophysin, and PSD-95 immunoreactivity), and greater expression of BDNF. It is unknown, but also expected that better behavioral recovery will coincide with a greater reduction in NOGO-A in the injured motor cortex. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies will aid in creating a model that will allow for a better understanding of the relationship between brain stimulation, severity of injury and, in future studies, aging. These studies will also help clarify previous conflicting brain stimulation results.